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Gut Microbiota: An Immersion in Dysbiosis, Associated Pathologies, and Probiotics

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18 March 2025

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19 March 2025

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Abstract
The importance of the microbiome, particularly the gut microbiota and its implications for health, is well established. However, an increasing number of studies further strengthen the link between an imbalanced gut microbiota and a greater predisposition to different diseases. The gut microbiota constitutes a fundamental ecosystem for maintaining human health. Its alteration, known as dysbiosis, is associated with a wide range of conditions, including intestinal, metabolic, immunological, or neurological pathologies, among others. In recent years, there has been a substantial increase in knowledge about probiotics—bacterial species that enhance health or address various diseases—with numerous studies reporting their benefits in preventing or improving these conditions. This review aims to analyze the most common pathologies resulting from an imbalance in the gut microbiota, as well as detail the most important and known gut probiotics, their functions, and mechanisms of action in relation to these conditions.
Keywords: 
gut microbiota
;  
probiotics
;  
dysbiosis
;  
intestinal diseases
;  
gut-brain axis
;  
metabolic disorders
Subject: 
Biology and Life Sciences  -   Immunology and Microbiology

1. Introduction

In a 70 kg human, the number of bacteria is approximately 3.8 x 10¹³, while the number of human cells is estimated at 3 x 10¹³ [1]. This makes the human body a true ecosystem where approximately 500-1000 bacterial species, with an estimated 2000 genes per species, coexist in symbiosis with our cells as a result of more than 500 million years of co-evolution [2,3]. The set of microorganisms that coexist in balance with our body is known as the microbiome. The microbiome plays a crucial role in host health by protecting against pathogenic microorganisms, modulating the immune response, contributing to neurotransmitter production, and participating in digestive processes such as fiber degradation [4].
The microbiome of a specific body part is referred to as the microbiota, and depending on its location, certain types of microorganisms will predominantly thrive. Thus, in the same person, the bacteria present on the skin, in the mouth, or in the intestine, will not be the same but it can be similar between different persons [5]. Additionally, the microbiome is unique to each individual and depends on factors such as genetics, age, gender, hygiene habits, stress, lifestyle, contact with nature, antibiotics use, or diet, among others [6]. Specifically, gut microbiome has a significant impact in human health, affecting nutrient absorption and influencing immune system or oxidative stress; in fact, it has been associated to metabolic syndrome and obesity [7,8,9].
A prolonged disturbance or imbalance in the microbiota can lead to dysbiosis, which is associated with various diseases [10]. In the mouth, dysbiosis can cause dental problems such as periodontal disease or the emergence of cariogenic bacteria like Streptococcus mutans [11,12]. In other organs, such as the intestine, dysbiosis can entail significantly more negative aspects, including digestive conditions such as colitis [13], or an increased risk of cardiovascular diseases [14] and neurological disorders [15]. Thus, these links between dysbiosis and disease are particularly evident and severe in the gut, where dysbiosis is associated with conditions such as inflammatory bowel disease (IBD) [16,17,18], metabolic disorders like obesity or diabetes [19], and various immune [20], neurological [21], and cardiovascular disorders [22].
To prevent such imbalances, we can consume prebiotics, substances that serve as nourishment for our beneficial microorganisms, or probiotics, non-pathogenic live microorganisms that offer certain health benefits [9,23]. This term was introduced by Élie Metchnikoff over 100 years ago, where he proposed the theory that manipulating the composition of the intestinal microbiota could benefit health [24]. The mechanisms by which probiotics inhibit the growth of other pathogenic bacteria and benefit us are diverse and depend on the specific probiotic strain. However, in general, they act by modifying the pH of the environment, producing antibacterial compounds and bacteriocins, competing for available nutrients and growth factors, or stimulating the host’s immune system [25,26]. Furthermore, to preventing the proliferation of other bacteria and generating dysbiosis, probiotics offer other health benefits, such as metabolizing indigestible fibers, producing vitamins and cofactors, promoting the production of anti-inflammatory cytokines and T-cell activity, and supporting intestinal barrier integrity, among others [26].
Due to the importance of the gut microbiota and its strong association with various pathologies, this review will examine the key relationships between gut microbiota and diseases linked to its dysbiosis, with an emphasis on how probiotics could improve or prevent the onset of these conditions.

2. Gut Microbiome and Usual Probiotics Strains

In humans, gut microbiome weights approximately 2 kg, being symbionts most of them [27]. The gut microbiota maintains a state of homeostasis in our body that prevents pathogen colonization, influences intestinal permeability, facilitates the metabolism of certain foods such as fibers and specific types of sugars, synthesizes vitamins like K, B-complex, and folate, and modulates the local immune response while also influencing systemic immunity [28].
The human gut microbiome is predominantly composed of four major phyla: Firmicutes (including genera such as Clostridium, Lactobacillus, Streptococcus, Enterococcus, and Eubacterium), Bacteroidetes (Bacteroides, Parabacteroides, and Provotella), Actinobacteria (Bifidobacterium and Collinsella), and Proteobacteria (Helicobacter and Escherichia). Additionally, two less abundant phyla, Verrucomicrobia (Akkermansia) and Fusobacteria (Fusobacterium), are also present. Collectively, Firmicutes and Bacteroidetes account for approximately 70 to 90% of the gut microbial population [29,30,31]. There are some differences between small intestine (duodenum, jejunum, and ileum) and large intestine (colon). The first group includes bacteria such as Enterococcus, Lactobacillus, Bacteroides, Bifidobacterium, Clostridium, and Enterobacteriaceae, while the second group comprises the same bacteria as the first, in addition to others such as Escherichia, Klebsiella, Peptococcus, Peptostreptococcus, Proteus, Staphylococcus, and Ruminococcus [32].
This standard microbiome can be modulated by prebiotics and/or probiotics. When probiotic consumed in adequate amounts, can colonize different parts of the digestive tract, protect the host from pathogenic microorganisms, and provide direct health benefits [10,26]. The world of probiotics is vast and it is in continuous growth. Evidence of this is the increasing volume of research and connections provided by the study of the gut microbiota and probiotics, which are closely linked to gastrointestinal disorders, immune diseases, and metabolic alterations, among others (Figure 1).
The two main genera of probiotic microorganisms are Lactobacillus and Bifidobacterium [33]. Other microorganisms less commonly used are Enterococcus, Streptococcus, Lactococcus, Pediococcus, Propionibacterium, and yeast like Saccharomyces (S. boulardii, and S. thermophilus) [25,34]. For more detailed species and benefits of the bacterial probiotics, see Table 1. In general, Lactobacillus and Bifidobacterium strains may improve metabolic outcomes by controlling glycemic levels, modulating the immune system, or inhibiting the destruction of pancreatic β-cells, thereby helping to prevent diabetes [35,36,37]. Furthermore, most bacteria of these genera also decrease intestinal pH through organic acid production, thereby inhibiting the growth of pathogenic bacteria, which usually prefer a neutral pH [38]. Even, some of these probiotic microorganisms can inhibit the production of pathogenic enzymes that catalyze the conversion of carcinogenic precursors into carcinogens [39].
All microorganisms considered to be probiotics must possess a series of characteristics: they must be able to withstand gastric and bile acids, colonize a specific location within the digestive tract, usually the intestine, produce compounds that are beneficial to our health, provide some health benefit, and inhibit the growth of pathogenic microorganisms [40,41]. Among the main health benefits of probiotics are the enhancement of the immune system and the reduction of the risk of cardiovascular, metabolic, or neurological disorders, which will be further developed in the following sections.
Table 1. Most relevant probiotic microorganisms with their action mechanisms and health benefits.
Table 1. Most relevant probiotic microorganisms with their action mechanisms and health benefits.
Genera Species Mechanisms of action/Benefits References
Lactobacillus acidophilus 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 16, 17 [25,36,42,43,44,45,46,47,48]
amylovorus 1, 2, 4, 6, 10 [49]
brevis 1, 3, 4, 6, 7, 9, 11, 13, 14 [48,50,51,52,53,54,55]
casei 1, 3, 4, 6, 7, 10, 11, 12, 16, 17 [36,48,56,57,58,59]
crispatus 1, 4, 13, 14 [60,61,62]
delbrueckii ssp. bulgarius 1, 3, 4, 6, 7, 10, 16 [44,48,63]
fermentum 1, 4, 5, 6, 7, 8, 10, 13 [48,54,64]
gasseri 1, 8 , 11, 13, 14 [36,65]
helveticus 1, 4, 5, 6, 7, 12, 13, 17 [36,47,57]
iners* 1, 13 [62,66]
jensenii 1, 4, 6, 7, 13 [62,67]
johnsonii 1, 4, 6, 7, 10 [44,68,69]
kefiranofaciens 1, 4, 6, 7, 11 [70]
paracasei 1, 6, 14, 15, 16 [45,71,72,73,74]
plantarum 1, 4, 6, 7, 10, 13, 14, 16 [25,54,74]
reuteri 1, 6, 9, 10, 13, 14, 17 [25,47,48,75,76]
rhamnosus 1, 3, 4, 7, 8, 10, 11, 12, 13, 14, 15, 17 [25,36,45,48,57,72,77]
salicinius 1, 13 [48]
salivarius 1, 9, 14 [36]
Bifidobacterium adolescentis 1, 4, 11, 17 [36,47,78,79]
animalis 1, 3, 4, 6, 11, 14, 16 [36,41,80]
breve 1, 4, 6, 10, 11, 17 [36,47,48,81,82]
bifidum 1, 2, 3, 4, 7, 10, 11, 14, 15, 17 [36,46,47,48,72,83]
dentium 1, 4, 7, 14 [72,84]
infantis 1, 3, 6, 10, 11, 17 [36,47,48,71,85]
lactis 1, 3, 4, 7, 10, 11, 15, 16, 17 [36,45,47,48,86,87]
longum 1, 3, 4, 6, 7, 10, 11, 17 [36,47,48,58,63,78]
pseudocatenulatum 1, 2, 4, 5, 11 [36,88,89,90,91,92]
thermophilum 1, 11, 14 [36,93]
Enterococcus durans** 1, 8 [94]
faecalis 1, 3, 4, 10 [48,95,96]
faecium 1, 9, 10 [25,97]
Lactococcus lactis ssp. cremoris** 1, 2, 4, 8, 16 [98,99,100]
lactis ssp. lactis** 1, 4, 8 [100,101,102]
lactis ssp. lactis bv. diacetylactis** 1, 2, 8, 9 [100,101,102]
Streptococcus salibarius 14 [103,104]
thermophilus** 1, 4, 6, 7, 9, 10 [48,71,105]
Propionibacterium acidipropionici** 1, 2 [34]
freudenreichii 1, 2, 3, 4, 6 [34,48,105,106]
jensenii** 1, 2 [34,107]
thoenii** 1, 2 [34,107]
Leuconostoc mesenteroides ssp. cremoris* 1, 4, 14 [105,108,109]
Pediococcus acidilactici 1, 4, 13, 17 [48,110]
pentosaceus 1, 3, 4, 8, 9 [111]
Adapted from [25,36,47,48,112]. Mechanisms of action/Benefits: 1 (decrease intestinal pH and regulate microflora/prevention of infections), 2 (produce metabolites/enzymes that improve nutrition), 3 (inhibit pathogenic/carcinogenic enzymes, anticarcinogenic properties), 4 (modulate immunity thought anti-inflammatory or pro-inflammatory cytokines), 5 (reduce cardiovascular diseases), 6 (beneficial role against intestinal diseases like inflammatory intestinal injury, ulcerative colitis, decline crypt depth), 7 (reduce oxidative stress/antioxidant activity), 8 (control cholesterol or lipid levels in blood), 9 (specific antibiotics/bacteriocins production), 10 (help against diarrhea), 11 (positive effect against metabolic diseases like obesity or diabetes), 12 (improve lung or kidney pathologies), 13 (positive implication in reproductive health), 14 (buccal health improvement), 15 (skin diseases improvement/atopic dermatitis treatment), 16 (reduce respiratory tract infections), 17 (prevention/improve of neural diseases or disorders). * Bacteria with a controversial role as probiotics. ** Promising possible probiotics.
Probiotics are consumed in diverse ways like dairy products, food supplements, and functional food. Typically, most of the mentioned probiotic microorganisms can be found in different types of dairy and fermented milk products, like yogurt, cheese, or kefir [113,114]. However, emerging market trends are opening doors to new types of products, including those based on traditional methods of preserving plant-based products, like fermentation with lactic acid bacteria [115]. Among the most common plant-based products containing probiotics are olives, pickles, soy, coffee, sauerkraut, ogi, and kimchi [116,117,118]. Additionally, certain unfiltered fermented alcoholic beverages that still retain some microorganisms, such as beer, wine, and kombucha, as well as bakery products primarily using yeasts, can serve as sources of probiotics [119,120]. Consuming probiotics in this manner can facilitate their intake and may also promote synergies between different microbial genera [121]. This is noteworthy because, typically, various species or genera can perform similar beneficial functions for our body. However, consuming them in combination may offer additional advantages, as highlighted by Esposito et al., who demonstrated that the combination of S. thermophilus with several species of Lactobacillus and Bifidobacteria, can limit oxidative and inflammatory damage in nonalcoholic fatty liver disease [121].

3. Gut Dysbiosis and How It Is Affected by Diet

Gut dysbiosis is characterized by an imbalance in the composition of the gut microbiota, specifically regarding the relative abundances of different bacteria. This imbalance can be linked to functional alterations in the microbial transcriptome, proteome, or metabolome [122]. Notably, disruption in the Bacteroidetes/Firmicutes ratio with increases in Enterobacterial populations, such as Escherichia coli, Klebsiella spp., and Proteus spp., are often seen in cases of gut dysbiosis [122].
A well-balanced gut microbiota is vital for maintaining intestinal stability and promoting human health. A wide range of both gastrointestinal and systemic conditions are linked to dysbiosis, such as IBD, obesity, diabetes, food allergies, asthma, colorectal cancer, among others [18,19,123,124] . Increasing evidence indicates that dysbiosis in the gut microbiota (for example higher proportion of Firmicutes [125]) and its metabolites can compromise the integrity of the intestinal barrier. This disruption occurs by inhibiting the expression of proteins that are crucial for maintaining intestinal tight junctions [17], resulting in a greater passage of lipopolysaccharides (LPS) from the intestine into the bloodstream, which in turn leads to metabolic endotoxemia [126].
Gut dysbiosis can result from changes in diet, immune deficiencies, infections, or exposure to antibiotics and toxins [127]. In particular, diet can be considered as the main factor influencing the gut microbiota throughout an individual’s life. In fact, nutrition is quite important from the earliest stages of life. Human breast milk, which is rich in oligosaccharides, supports the growth of bacteria that can process carbohydrates, like Bifidobacterium and Bacteroides species [128,129]. This leads to a distinct gut microbiota profile in breastfed infants, while formula-fed infants tend to have higher levels of Clostridium spp. [128,129].
In adulthood, different types of diets can potentially influence the relative abundance of bacteria in the gut. On the one hand, Western diets that are high in fats and carbohydrates can lead to severe dysbiosis [130], decreasing the Bacteroidetes/Firmicutes ratio [130,131]. In a study conducted on mice, the gut microbiota of the low-fat diet group consisted of 61% Firmicutes and 32% Bacteroidetes, while the high-fat diet group showed a composition of 73% Firmicutes and 21% Bacteroidetes [132]. This shift has been associated with increased intestinal permeability and, consequently, with different metabolic disorders, such as obesity and type 2 diabetes, among others [130,133].
On the other hand, Mediterranean and vegetarian diets, with a lot of fruits, vegetables, olive oil, and oily fish, are known for their anti-inflammatory properties and might help prevent dysbiosis and the development of IBD [16,17]. In these types of diets, in addition to a greater Bacteroidetes/Firmicutes ratio, there are higher levels of short-chain fatty acid (SCFA) producers and a slight decrease in intestinal pH, preventing the growth of potential pathogenic Enterobacteria, such as E. coli and others [134]. In addition, the intestinal microbiota has been reported to change depending on the type of fatty acid ingested. Omega-3 polyunsaturated fatty acids intake, characteristic of a Mediterranean diet, was directly associated with an increase in Lactobacillus abundance, while monounsaturated and omega-6 polyunsaturated fatty acids were related to decreased Bifidobacterium [135].
For all these reasons, probiotics have gained significant importance in recent years. These beneficial microorganisms play a key role in supporting a balanced gut microbiota, which is crucial for proper digestion, immune function, and even mental health. As lifestyle changes and dietary habits, such as the consumption of processed foods, lead to a higher prevalence of gut dysbiosis, the demand for probiotic supplements and probiotic-rich foods grows. Their potential to prevent or manage different conditions has made them an increasingly valuable component of modern health strategies.

4. Intestinal Diseases and Relation with Probiotics

IBD, such as Crohn’s disease or ulcerative colitis, are complex conditions with multiple contributing factors. Around 3.7 million individuals in Europe and United States of America are affected by IBD [136]. These chronic, progressive immune disorders are associated with changes in microbiota composition, or dysbiosis, and an impaired mucosal barrier, which lead to excessive immunologic responses at the mucosal level [16]. Particularly, IBD is characterized by chronic inflammation, along with a concomitant production of elevated levels of pro-inflammatory cytokines and free radicals such as nitric oxide, which are likely involved in intestinal tissue injury [71,137]. Under normal physiological conditions, nitric oxide plays a role in the intestinal antibacterial response; for example, enteroinvasive bacteria like E. coli, Salmonella, and Shigella can directly induce inducible nitric oxide synthase (iNOS) expression as part of the host defense mechanism [138]. However, nitric oxide may occasionally become part of a dysregulated immune response, resulting in chronic inflammatory disorders such as IBD [139].
Studies with humans have determined different microbiota composition between IBD patients and healthy ones [140]. SCFA like propionic acid exhibit anti-inflammatory properties, and a reduction in SCFA-producing Phascolarctobacterium has been observed in IBD, exacerbating its symptoms [140]. Moreover, individuals with Chron’s disease or ulcerative colitis reported a reduction in anti-inflammatory bacteria, such as F. prausnitzii, in their fecal microbiota compared to healthy subjects [141,142]. However, it remains uncertain whether this reduction is a cause or a consequence of IBD.
Different probiotics have been tested to treat chronic diseases, mainly due to their ability to modulate the immune system and elicit an anti-inflammatory response by downregulating the production of inflammatory cytokines. Mice with dextran sulfate sodium (DSS)-induced colitis were treated with L. acidophilus, B. lactis, L. plantarum, and B. breve for 7 days [71]. This treatment improved clinical symptoms, histological alterations, and mucus production. In addition, probiotic supplementation decreased nitric oxide production by peritoneal macrophages compared to healthy mice [71]. Regarding human studies, patients with ulcerative colitis received twice daily for 12 weeks a probiotic preparation of 4 strains of Lactobacillus (L. paracasei, L. plantarum, L. acidophilus, and L. delbrueckii subspecies bulgaricus), 3 strains of Bifidobacterium (B. longum, B. breve, and B. infantis), and 1 strain of S. thermophilus, achieving a higher remission rate than control group [143]. However, the treatment of IBD with probiotics in humans is controversial, as various clinical studies have not reported significant improvements in these patients [144,145]. This is not surprising, considering that IBD is a multifactorial disease and the microbiota is potentially influenced by diet, antibiotics, and other factors.
Currently, there is ongoing research into the use of engineered probiotics that could act as ‘sense and respond’ systems (biosensor and biotherapeutic) [146]. These engineered probiotics would be bacteria carrying transfected plasmids encoding for immunoregulatory cytokines or anti-inflammatory mediators [146,147]. This approach aims to reduce the need for chronic immunosuppressive treatments and frequent invasive, costly procedures [146]. Nevertheless, further research is necessary to determine if personalized therapy for IBD is feasible.
Another condition in which there is an imbalance in the gut microbiota is small intestinal bacterial overgrowth (SIBO). This is common in patients with irritable bowel syndrome and its diagnosis requires a hydrogen breath test, which detects hydrogen released from the fermentation of carbohydrates by gut bacteria [148]. The usual choice for managing SIBO is antibiotics; nevertheless, it is not always effective and patients relapse after treatment [148]. Probiotics are emerging as a new approach to treat SIBO together with antibiotics; in fact, a meta-analysis has reported that probiotics improve SIBO by increasing the decontamination rate, reducing hydrogen concentration, and alleviating abdominal pain [149]. The probiotics studied included strains of Lactobacillus (such as L. casei, L. acidophilus, L. rhamnosus), Bifidobacterium (B. breve, B. longum, B. infantis), and Bacillus clausii, among others, either alone or in combination with antibiotics. However, probiotics were not effective in preventing SIBO [149].

5. Dysbiosis and Probiotics in Metabolic Disorders

Obesity is a major public health issue today, influenced by a variety of factors and often associated with insulin resistance, which can lead to type 2 diabetes. A common underlying cause of obesity is an imbalance between energy intake and energy expenditure [19]. Emerging evidence indicates that this imbalance might be linked to an altered gut microbiota [150], as the gut’s bacterial communities play crucial roles in processes like digestion, nutrient absorption, and energy regulation [19]. In fact, studies have shown that, compared to lean mice, the gut microbiota in obese mice tends to have a lower proportion of Bacteroidetes and a higher proportion of Firmicutes [150].
Dysbiosis associated with obesity is closely tied to a high-fat diet and is characterized by a shift in the abundance of specific bacterial species and increased gut permeability [151,152]. The heightened intestinal permeability allows LPS to enter the bloodstream, leading to elevated levels that cause metabolic endotoxemia. This phenomenon is commonly observed in individuals with obesity, insulin resistance, or type 2 diabetes [153,154,155]. LPS are known for their pro-inflammatory properties, as they activate Toll-like receptors 4 (TLR4), nucleotide-binding oligomerization domain expression, and inflammasomes, which in turn promote the maturation of pro-inflammatory cytokines [19]. Consequently, chronic low-grade inflammation, changes in SCFA metabolism, and other factors like genetic predisposition, lifestyle, and diet, can drive the progression of metabolic disorders, such as obesity and insulin resistance.
The gut microbiota in obesity is characterized by the presence of genes that enhance energy harvest and metabolism, particularly those that encode enzymes for breaking down complex plant polysaccharides into SCFA [19]. These SCFA serve both as an energy source and as signaling molecules, influencing processes as lipogenesis, fat storage, fatty acid oxidation, and gluconeogenesis [156]. SCFA, along with other microbial metabolites, are part of a balanced microbiota and promote gut health. Nevertheless, in the context of obesity, an imbalance in the microbiota can lead to elevated SCFA levels in the bloodstream, providing an extra energy source that may promote de novo lipogenesis in the liver [19]. The question remains whether higher SCFA levels in obese individuals are a cause or a consequence of such condition.
Interventions using prebiotics and probiotics together can work synergistically to restore microbiota balance, reduce inflammation, and improve insulin resistance. Several clinical trials have shown that Lactobacillus and Bifidobacterium strains may help prevent metabolic disorders, including obesity [157,158]. A systematic review of 16676 overweight and obese adults found that probiotics had a moderate effect on reducing body weight; however, these beneficial effects were only observed when probiotics were used in high doses [159]. In addition, patients with type 2 diabetes were randomized to receive either 300 g of probiotic yogurt containing L. acidophilus La5 and B. lactis Bb12 or 300 g of conventional yogurt for 6 weeks. Probiotic consumption led to significant decreases in total cholesterol, low-density lipoprotein cholesterol (LDL-C), and atherogenic indices compared to controls, suggesting an improvement in cardiovascular disease risk factors [160].
Prebiotics like oligofructose, long-chain inulin, or β-glucans have also demonstrated not only improvements in gut microbiota but beneficial effects on metabolic disorders. A randomized controlled trial found that supplementing with oligofructose-enriched inulin helped manage pediatric overweight and obesity by improving appetite control and reducing energy intake in children aged 11-12 [161]. The authors emphasize the need for further research to clarify the mechanisms behind these physiological effects. One proposed explanation is enhanced satiety, as SCFA bind to specific receptors on colonic L-cells (free fatty acid receptors or FFAR), stimulating the release of appetite-regulating hormones [162]. In addition, type 2 diabetic women who received a daily dose of 10 g of oligofructose-enriched inulin showed significant improvements in glycemic status, lipid profile, and immune markers [163].

6. Probiotics in the Modulation of the Gut-Brain Axis

The relationship between the intestine, gut microbiome, and brain diseases has rapidly increased in the last 15 years, with the gut microbiome sometimes being a key factor in the susceptibility and development of certain pathologies such as Alzheimer’s disease, Parkinson’s disease, autism, and multiple sclerosis [21,164]. Gut microbial exhibits an important place in the crosstalk between the gut and the brain though the vagus nerve. Several theories have been proposed to explain the communication pathways between the gut and the brain, including the neuroendocrine hypothalamic-pituitary-adrenal axis, the neuroanatomical gut-brain axis, the gut immune system, the gut microbiota metabolism system, the intestinal mucosal barrier, and the blood-brain barrier [165,166]. The gut microbiota participates in this communication by synthesizing neurotransmitters such as gamma-aminobutyric acid (GABA), catecholamines, serotonin, acetylcholine, and dopamine, which may modify host neuronal activity. Additionally, it produces short-chain fatty acids (SCFAs), primarily acetate, propionate, and butyrate [167,168]. Moreover, it can reduce cortisol levels, lipid peroxidation, and monoamine oxidase activity or modulate specific minerals in tissues, such as magnesium and zinc [169,170,171].
The connection between dysbiosis and inflammation it generates has already been discussed. This inflammation can lead to an acceleration of certain diseases, where a pro-neuroinflammatory environment worsens diseases progression [172]. However, some diseases go beyond merely worsening the prognosis, being directly associated with specific dysbiosis [173]. On the one hand, numerous clinical studies have found that dysbiosis in the small intestine can influence the progression of Parkinson’s disease, by increasing neuroinflammation and α-synuclein aggregation, or by decreasing SCFA levels [15]. These SCFA are activators of G protein-coupled receptors, inhibiting histone deacetylases and leading to epigenetic regulation of antioxidant genes and redox signaling. Also, some SCFA have shown protective activity against dopaminergic neuron loss, while inhibiting neuroinflammation and the motor dysfunction characteristic of Parkinson’s disease [174,175,176]. On the other hand, increases in pathogenic bacteria such as Escherichia or Shigella have been linked to elevated levels of pro-inflammatory cytokines such as C-X-C motif chemokine ligand 2 (CXCL2), interleukins (IL-1β, IL-6), or inflammasome complexes (NLR family pyrin domain containing 3 or NLRP3) in patients with brain amyloidosis—an accumulation of amyloid proteins in the brain—worsening the pathogenesis of Alzheimer’s disease [177].
Similarly, just as an imbalance in the gut microbiome can lead to or accelerate the progression of a neurological disease, the use of probiotics can be employed to regulate certain neuronal pathologies. For example, L. plantarum can reduce α-synuclein accumulation in the substantia nigra in Parkinson’s disease, while B. animalis and L. acidophilus have been shown to rescue nigral dopaminergic neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and rotenone-induced neurotoxicity [178]. Generally, these approaches involve administering probiotics or fecal microbiota transplantation to the patient, which can lead to SCFA production in the intestine, helping to reduce intestinal inflammation in Parkinson’s disease and α-synuclein aggregation [179]. Moreover, new applications for probiotics are emerging, providing mental health benefits by inducing metabolites, hormones, and immune factors, and by exhibiting antidepressant and anxiolytic activity; thus, falling under the category of psychobiotics [180]. For example, B. breve has improved cognitive function in older adults with suspected mild cognitive impairment [82], L. rhamnosus has shown anxiolytic capacity [77], L. casei has decreased anxiety [59], and B. infantis has normalized behavior [85].
Lastly, probiotics can mitigate the imbalance caused by antibiotic use, which can lead to neuronal changes. In mice, treatment with ampicillin has been shown to reduce intestinal populations of Lactobacillus, Bifidobacterium, Clostridium, and Firmicutes, resulting in decreased intestinal crypt depth and villous length, as well as impairments in cognition and hippocampal neuronal density. Furthermore, antibiotic treatment also increased corticohippocampal acetylcholinesterase activity, myeloperoxidase activity, and oxidative stress. These changes were partially reversed by treatment with the probiotic Bifilac, which contains L. sporogenes, C. butyricum, S. faecalis, and B. mesentericus [181].

7. Probiotics in the Immune System

In this review, we have observed how the intestinal microbiota, and consequently probiotics, are associated with various intestinal, metabolic, and neurological diseases. Many of these diseases are interconnected through the immune system or by the disruption of the gut barrier due to dysbiosis [182]. On the one hand, the gut microbiota can influence innate immunity. As mentioned earlier, increased intestinal permeability can lead to elevated levels of LPS in the bloodstream, triggering a pro-inflammatory state. LPS activate TLR4, leading to the activation of nuclear factor kappa B (NF-κB) signaling and the production of pro-inflammatory cytokines (tumor necrosis factor alpha or TNF-α, IL-1β, IL-6) [19,183]. Additionally, other microbial components can stimulate nucleotide-binding oligomerization domain proteins and inflammasomes, further promoting inflammatory responses [19]. On the other hand, the intestinal microbiota can also impact adaptive immunity by influencing secretory IgA levels. Certain bacterial species have been associated with lower secretory IgA levels [184], which may compromise mucosal immunity and alter host-microbiota interaction [185]. However, rather than direct degradation of IgA by the microbiota, this effect may be due to broader immune system dysregulation.
Probiotics like B. animalis, L. acidophilus, L casei, L. johnsonii, or L. rhamnosus can enhance innate and nonspecific cellular immune responses thought the activation of macrophages, dendritic cells, TLR, natural killer cells, and B or T lymphocytes [20]. On the one hand, in rats, L. acidophilus has been reported to inhibit the expression of the Niemann-Pick C1-like 1 (NPC1L1) gene in the small intestine and regulate levels of oxidized LDL, superoxide dismutase (SOD), TNF-α, and IL-10, thereby suppressing inflammation and oxidative stress, and inhibiting the development of atherosclerosis effects [42]. Furthermore, L. acidophilus strains ATCC 314 and PTCC 1643 have exerted anti-inflammatory properties in an arthritis rat model and modulated the expression of TLR2 and TLR4 in HT29 intestinal epithelial cells [42]. On the other hand, in mice, oral administration of L. casei induced an early innate immune response, increasing CD206, a receptor of macrophages and dendritic cells, and TLR2 markers [186].
In humans, different species and strains of Lactobacillus and Bifidobacterium have shown an increase in anti-Salmonella typhi antibody response and serum IgA levels [187,188], an increase in serum IgG during early response (0-21 days), and an increase in IgA and IgM in late response (21-28 days) [189]. Finally, L. reuteri reduced pro-inflammatory cytokines such as TNF-α, IL-1, and IL-8, proposing an effective probiotic treatment against distal ulcerative colitis [190].

8. Conclusions

The current knowledge of the human microbiome, its interactions with various diseases, and how probiotics can improve or prevent these diseases is rapidly expanding. This progress is driven, in part, by advancements in sequencing techniques and the integration of various omics data, including transcriptomics, proteomics, metabolomics, and immunomics. As these foundations solidify and knowledge about beneficial microorganisms for human health grows, the accessibility and utilization of probiotics will continue to increase across populations.
The microbiota and the interactions between probiotic microorganisms and human health represent a complex field of study. Each individual possesses a distinct microbiome, which becomes even more complex when analyzing strain-specific effects due to the enormous variability involved. Nevertheless, certain general principles tend to hold, such as which types of microorganisms are beneficial versus pathogenic, the balance that should exist between Bacteroidetes and Firmicutes populations, and the importance of a healthy microbiome in preventing the progression of certain diseases.
This review addresses numerous diseases across major pathological groups, organized by affected tissues; however, two common threads emerge: the relationship with the immune system and the induction of inflammation, as well as the appearance of other pathogenic microorganisms that may independently trigger additional diseases. Thus, much remains to be explored regarding the microbiome’s interactions with rare or lesser-known inflammatory diseases and complex, multifactorial conditions, such as neurological diseases and the gut-brain axis.
The future of probiotics in nutrition holds promising potential for advancing health and disease prevention. As scientific understanding deepens, probiotics may be tailored to address individual microbiome compositions, enhancing personalized health strategies or even aiding in the prevention and treatment of diseases.

Author Contributions

Writing, review, editing, and revision, V.O. and A.L.Z.; conceptualization, supervision, and validation, A.L.Z. All authors have read and agreed to the published version of the manuscript.

Funding

Not applicable.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

Author Alvaro Lopez-Zaplana was employed by the company 3A Biotech. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

  1. Sender, R.; Fuchs, S.; Milo, R. Revised Estimates for the Number of Human and Bacteria Cells in the Body. PLoS Biol 2016, 14. [Google Scholar] [CrossRef] [PubMed]
  2. Ley, R.E.; Hamady, M.; Lozupone, C.; Turnbaugh, P.J.; Ramey, R.R.; Bircher, J.S.; Schlegel, M.L.; Tucker, T.A.; Schrenzel, M.D.; Knight, R.; et al. Evolution of Mammals and Their Gut Microbes. Science 2008, 320, 1647–1651. [Google Scholar] [CrossRef]
  3. Turnbaugh, P.J.; Ley, R.E.; Hamady, M.; Fraser-Liggett, C.M.; Knight, R.; Gordon, J.I. The Human Microbiome Project. Nature 2007, 449, 804–810. [Google Scholar] [CrossRef]
  4. Gilbert, J.A.; Blaser, M.J.; Caporaso, J.G.; Jansson, J.K.; Lynch, S. V.; Knight, R. Current Understanding of the Human Microbiome. Nat Med 2018, 24, 392–400. [Google Scholar] [CrossRef]
  5. Maki, K.A.; Kazmi, N.; Barb, J.J.; Ames, N. The Oral and Gut Bacterial Microbiomes: Similarities, Differences, and Connections. Biol Res Nurs 2021, 23, 7–20. [Google Scholar] [CrossRef] [PubMed]
  6. Mallott, E.K.; Sitarik, A.R.; Leve, L.D.; Cioffi, C.; Camargo, C.A.; Hasegawa, K.; Bordenstein, S.R. Human Microbiome Variation Associated with Race and Ethnicity Emerges as Early as 3 Months of Age. PLoS Biol 2023, 21. [Google Scholar] [CrossRef]
  7. Le Chatelier, E.; Nielsen, T.; Qin, J.; Prifti, E.; Hildebrand, F.; Falony, G.; Almeida, M.; Arumugam, M.; Batto, J.M.; Kennedy, S.; et al. Richness of Human Gut Microbiome Correlates with Metabolic Markers. Nature 2013, 500, 541–546. [Google Scholar] [CrossRef] [PubMed]
  8. Tilg, H.; Moschen, A.R. Gut Microbiome, Obesity, and Metabolic Syndrome. Metabolic Syndrome 2023, 373–384. [Google Scholar] [CrossRef]
  9. Bock, P.M.; Martins, A.F.; Schaan, B.D. Understanding How Pre- and Probiotics Affect the Gut Microbiome and Metabolic Health. Am J Physiol Endocrinol Metab 2024, 327, E89–E102. [Google Scholar] [CrossRef]
  10. Lloyd-Price, J.; Abu-Ali, G.; Huttenhower, C. The Healthy Human Microbiome. Genome Med 2016, 8. [Google Scholar] [CrossRef]
  11. Cugini, C.; Ramasubbu, N.; Tsiagbe, V.K.; Fine, D.H. Dysbiosis From a Microbial and Host Perspective Relative to Oral Health and Disease. Front Microbiol 2021, 12. [Google Scholar] [CrossRef] [PubMed]
  12. Koga-Ito, C.Y.; Martins, C.A.P. de; Balducci, I.; Jorge, A.O.C. Correlation among Mutans Streptococci Counts, Dental Caries, and IgA to Streptococcus Mutans in Saliva. Braz Oral Res 2004, 18, 350–355. [Google Scholar] [CrossRef] [PubMed]
  13. Moutsopoulos, N.M.; Konkel, J.E. Healthy Mouth, Healthy Gut: A Dysbiotic Oral Microbiome Exacerbates Colitis. Mucosal Immunol 2020, 13, 852–854. [Google Scholar] [CrossRef]
  14. Tonelli, A.; Lumngwena, E.N.; Ntusi, N.A.B. The Oral Microbiome in the Pathophysiology of Cardiovascular Disease. Nat Rev Cardiol 2023, 20, 386–403. [Google Scholar] [CrossRef] [PubMed]
  15. Kalyanaraman, B.; Cheng, G.; Hardy, M. Gut Microbiome, Short-Chain Fatty Acids, Alpha-Synuclein, Neuroinflammation, and ROS/RNS: Relevance to Parkinson’s Disease and Therapeutic Implications. Redox Biol 2024, 71. [Google Scholar] [CrossRef]
  16. Tomasello, G.; Mazzola, M.; Leone, A.; Sinagra, E.; Zummo, G.; Farina, F.; Damiani, P.; Cappello, F.; Geagea, A.G.; Jurjus, A.; et al. Nutrition, Oxidative Stress and Intestinal Dysbiosis: Influence of Diet on Gut Microbiota in Inflammatory Bowel Diseases. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2016, 160, 461–466. [Google Scholar] [CrossRef]
  17. Chae, Y.R.; Lee, Y.R.; Kim, Y.S.; Park, H.Y. Diet-Induced Gut Dysbiosis and Leaky Gut Syndrome. J Microbiol Biotechnol 2024, 34, 747. [Google Scholar] [CrossRef]
  18. Santana, P.T.; Rosas, S.L.B.; Ribeiro, B.E.; Marinho, Y.; de Souza, H.S.P. Dysbiosis in Inflammatory Bowel Disease: Pathogenic Role and Potential Therapeutic Targets. Int J Mol Sci 2022, 23, 3464. [Google Scholar] [CrossRef]
  19. Moszak, M.; Szulińska, M.; Bogdański, P. You Are What You Eat—The Relationship between Diet, Microbiota, and Metabolic Disorders—A Review. Nutrients 2020, 12, 1096. [Google Scholar] [CrossRef]
  20. Ashraf, R.; Shah, N.P. Immune System Stimulation by Probiotic Microorganisms. Crit Rev Food Sci Nutr 2014, 54, 938–956. [Google Scholar] [CrossRef]
  21. Cryan, J.F.; O’Riordan, K.J.; Sandhu, K.; Peterson, V.; Dinan, T.G. The Gut Microbiome in Neurological Disorders. Lancet Neurol 2020, 19, 179–194. [Google Scholar] [CrossRef] [PubMed]
  22. Lau, K.; Srivatsav, V.; Rizwan, A.; Nashed, A.; Liu, R.; Shen, R.; Akhtar, M. Bridging the Gap between Gut Microbial Dysbiosis and Cardiovascular Diseases. Nutrients 2017, 9. [Google Scholar] [CrossRef] [PubMed]
  23. Bäckhed, F.; Fraser, C.M.; Ringel, Y.; Sanders, M.E.; Sartor, R.B.; Sherman, P.M.; Versalovic, J.; Young, V.; Finlay, B.B. Defining a Healthy Human Gut Microbiome: Current Concepts, Future Directions, and Clinical Applications. Cell Host Microbe 2012, 12, 611–622. [Google Scholar] [CrossRef]
  24. Metchnikoff, É. The Prolongation of Life; New York: Putnam, 1908. [Google Scholar]
  25. Parvez, S.; Malik, K.A.; Ah Kang, S.; Kim, H.Y. Probiotics and Their Fermented Food Products Are Beneficial for Health. J Appl Microbiol 2006, 100, 1171–1185. [Google Scholar] [CrossRef]
  26. Chugh, B.; Kamal-Eldin, A. Bioactive Compounds Produced by Probiotics in Food Products. Curr Opin Food Sci 2020, 32, 76–82. [Google Scholar] [CrossRef]
  27. Anwar, H.; Irfan, S.; Hussain, G.; Faisal, M.N.; Muzaffar, H.; Mustafa, I.; Mukhtar, I.; Malik, S.; Ullah, M.I. Gut Microbiome: A New Organ System in Body. Parasitol Microbiol Res 2019, 1, 17–21. [Google Scholar]
  28. Jandhyala, S.M.; Talukdar, R.; Subramanyam, C.; Vuyyuru, H.; Sasikala, M.; Reddy, D.N. Role of the Normal Gut Microbiota. World J Gastroenterol 2015, 21, 8836–8847. [Google Scholar] [CrossRef]
  29. Huttenhower, C.; Gevers, D.; Knight, R.; Abubucker, S.; Badger, J.H.; Chinwalla, A.T.; Creasy, H.H.; Earl, A.M.; Fitzgerald, M.G.; Fulton, R.S.; et al. Structure, Function and Diversity of the Healthy Human Microbiome. Nature 2012, 486, 207–214. [Google Scholar] [CrossRef]
  30. Fujisaka, S.; Watanabe, Y.; Tobe, K. The Gut Microbiome: A Core Regulator of Metabolism. Journal of Endocrinology 2023, 256. [Google Scholar] [CrossRef]
  31. Hajela, N.; Ramakrishna, B.S.; Nair, G.B.; Abraham, P.; Gopalan, S.; Ganguly, N.K. Gut Microbiome, Gut Function, and Probiotics: Implications for Health. Indian J Gastroenterol 2015, 34, 93–107. [Google Scholar] [CrossRef]
  32. Neffe-Skocińska, K.; Rzepkowska, A.; Szydłowska, A.; Kołozyn-Krajewska, D. Trends and Possibilities of the Use of Probiotics in Food Production. Alternative and Replacement Foods 2018, 17, 65–94. [Google Scholar] [CrossRef]
  33. Azad, M.A.K.; Sarker, M.; Li, T.; Yin, J. Probiotic Species in the Modulation of Gut Microbiota: An Overview. Biomed Res Int 2018, 2018. [Google Scholar] [CrossRef] [PubMed]
  34. Campaniello, D.; Bevilacqua, A.; Sinigaglia, M.; Altieri, C. Screening of Propionibacterium Spp. for Potential Probiotic Properties. Anaerobe 2015, 34, 169–173. [Google Scholar] [CrossRef]
  35. Lee, N.K.; Kim, W.S.; Paik, H.D. Bacillus Strains as Human Probiotics: Characterization, Safety, Microbiome, and Probiotic Carrier. Food Sci Biotechnol 2019, 28, 1297–1305. [Google Scholar] [CrossRef]
  36. Aggarwal, J.; Swami, G.; Kumar, M. Probiotics and Their Effects on Metabolic Diseases: An Update. J Clin Diagn Res 2013, 7, 173–177. [Google Scholar] [CrossRef] [PubMed]
  37. Gomes, A.C.; Bueno, A.A.; De Souza, R.G.M.H.; Mota, J.F. Gut Microbiota, Probiotics and Diabetes. Nutr J 2014, 13. [Google Scholar] [CrossRef]
  38. Bennett, A.; Eley, K.G. Intestinal PH and Propulsion: An Explanation of Diarrhoea in Lactase Deficiency and Laxation by Lactulose. J Pharm Pharmacol 1976, 28, 192–195. [Google Scholar] [CrossRef]
  39. Chang, J.H.; Shim, Y.Y.; Cha, S.K.; Reaney, M.J.T.; Chee, K.M. Effect of Lactobacillus Acidophilus KFRI342 on the Development of Chemically Induced Precancerous Growths in the Rat Colon. J Med Microbiol 2012, 61, 361–368. [Google Scholar] [CrossRef]
  40. Ranadheera, R.D.C.S.; Baines, S.K.; Adams, M.C. Importance of Food in Probiotic Efficacy. Food Research International 2010, 43, 1–7. [Google Scholar] [CrossRef]
  41. Jungersen, M.; Wind, A.; Johansen, E.; Christensen, J.E.; Stuer-Lauridsen, B.; Eskesen, D. The Science behind the Probiotic Strain Bifidobacterium Animalis Subsp. Lactis BB-12(®). Microorganisms 2014, 2, 92–110. [Google Scholar] [CrossRef]
  42. Gao, H.; Li, X.; Chen, X.; Hai, D.; Wei, C.; Zhang, L.; Li, P. The Functional Roles of Lactobacillus Acidophilus in Different Physiological and Pathological Processes. J Microbiol Biotechnol 2022, 32, 1226–1233. [Google Scholar] [CrossRef] [PubMed]
  43. Isazadeh, A.; Hajazimian, S.; Shadman, B.; Safaei, S.; Bedoustani, A.B.; Chavoshi, R.; Shanehbandi, D.; Mashayekhi, M.; Nahaei, M.; Baradaran, B. Anti-Cancer Effects of Probiotic Lactobacillus Acidophilus for Colorectal Cancer Cell Line Caco-2 through Apoptosis Induction. Pharmaceutical Sciences 2021, 27, 262–267. [Google Scholar] [CrossRef]
  44. Neish, A.S. Probiotics of the Acidophilus Group: Lactobacillus Acidophilus, Delbrueckii Subsp. Bulgaricus and Johnsonii. The Microbiota in Gastrointestinal Pathophysiology: Implications for Human Health, Prebiotics, Probiotics, and Dysbiosis 2017, 71–78. [Google Scholar] [CrossRef]
  45. Andrade, P.D.S.M.A. de; Maria e Silva, J.; Carregaro, V.; Sacramento, L.A.; Roberti, L.R.; Aragon, D.C.; Carmona, F.; Roxo-Junior, P. Efficacy of Probiotics in Children and Adolescents With Atopic Dermatitis: A Randomized, Double-Blind, Placebo-Controlled Study. Front Nutr 2022, 8. [Google Scholar] [CrossRef] [PubMed]
  46. Kim, J.Y.; Kwon, J.H.; Ahn, S.H.; Lee, S. Il; Han, Y.S.; Choi, Y.O.; Lee, S.Y.; Ahn, K.M.; Ji, G.E. Effect of Probiotic Mix (Bifidobacterium Bifidum, Bifidobacterium Lactis, Lactobacillus Acidophilus) in the Primary Prevention of Eczema: A Double-Blind, Randomized, Placebo-Controlled Trial. Pediatr Allergy Immunol 2010, 21. [Google Scholar] [CrossRef]
  47. Li, J.; Wang, J.; Wang, M.; Zheng, L.; Cen, Q.; Wang, F.; Zhu, L.; Pang, R.; Zhang, A. Bifidobacterium: A Probiotic for the Prevention and Treatment of Depression. Front Microbiol 2023, 14. [Google Scholar] [CrossRef]
  48. Uriot, O.; Denis, S.; Junjua, M.; Roussel, Y.; Dary-Mourot, A.; Blanquet-Diot, S. Streptococcus Thermophilus: From Yogurt Starter to a New Promising Probiotic Candidate? J Funct Foods 2017, 37, 74–89. [Google Scholar] [CrossRef]
  49. Shen, J.; Zhang, J.; Zhao, Y.; Lin, Z.; Ji, L.; Ma, X. Tibetan Pig-Derived Probiotic Lactobacillus Amylovorus SLZX20-1 Improved Intestinal Function via Producing Enzymes and Regulating Intestinal Microflora. Front Nutr 2022, 9. [Google Scholar] [CrossRef]
  50. Yakabe, T.; Moore, E.L.; Yokota, S.; Sui, H.; Nobuta, Y.; Fukao, M.; Palmer, H.; Yajima, N. Safety Assessment of Lactobacillus Brevis KB290 as a Probiotic Strain. Food Chem Toxicol 2009, 47, 2450–2453. [Google Scholar] [CrossRef]
  51. Rushdy, A.A.; Gomaa, E.Z. Antimicrobial Compounds Produced by Probiotic Lactobacillus Brevis Isolated from Dairy Products. Ann Microbiol 2013, 63, 81–90. [Google Scholar] [CrossRef]
  52. Abdelazez, A.; Abdelmotaal, H.; Evivie, S.E.; Melak, S.; Jia, F.F.; Khoso, M.H.; Zhu, Z.T.; Zhang, L.J.; Sami, R.; Meng, X.C. Screening Potential Probiotic Characteristics of Lactobacillus Brevis Strains In Vitro and Intervention Effect on Type I Diabetes In Vivo. Biomed Res Int 2018, 2018. [Google Scholar] [CrossRef] [PubMed]
  53. Lee, Y.; Kim, N.; Werlinger, P.; Suh, D.A.; Lee, H.; Cho, J.H.; Cheng, J. Probiotic Characterization of Lactobacillus Brevis MJM60390 and In Vivo Assessment of Its Antihyperuricemic Activity. J Med Food 2022, 25, 367–380. [Google Scholar] [CrossRef] [PubMed]
  54. Ramos, C.L.; Thorsen, L.; Schwan, R.F.; Jespersen, L. Strain-Specific Probiotics Properties of Lactobacillus Fermentum, Lactobacillus Plantarum and Lactobacillus Brevis Isolates from Brazilian Food Products. Food Microbiol 2013, 36, 22–29. [Google Scholar] [CrossRef] [PubMed]
  55. Pourbaferani, M.; Modiri, S.; Norouzy, A.; Maleki, H.; Heidari, M.; Alidoust, L.; Derakhshan, V.; Zahiri, H.S.; Noghabi, K.A. A Newly Characterized Potentially Probiotic Strain, Lactobacillus Brevis MK05, and the Toxicity Effects of Its Secretory Proteins Against MCF-7 Breast Cancer Cells. Probiotics Antimicrob Proteins 2021, 13, 982–992. [Google Scholar] [CrossRef]
  56. Zhu, H.; Cao, C.; Wu, Z.; Zhang, H.; Sun, Z.; Wang, M.; Xu, H.; Zhao, Z.; Wang, Y.; Pei, G.; et al. The Probiotic L. Casei Zhang Slows the Progression of Acute and Chronic Kidney Disease. Cell Metab 2021, 33, 1926–1942.e8. [Google Scholar] [CrossRef]
  57. Dashtbanei, S.; Keshtmand, Z. A Mixture of Multi-Strain Probiotics (Lactobacillus Rhamnosus, Lactobacillus Helveticus, and Lactobacillus Casei) Had Anti-Inflammatory, Anti-Apoptotic, and Anti-Oxidative Effects in Oxidative Injuries Induced By Cadmium in Small Intestine and Lung. Probiotics Antimicrob Proteins 2023, 15. [Google Scholar] [CrossRef]
  58. Lee, J.-W.; Shin, J.-G.; Kim, E.H.; Kang, H.E.; Yim, I.B.; Kim, J.Y.; Joo, H.-G.; Woo, H.J. Immunomodulatory and Antitumor Effects in Vivo by the Cytoplasmic Fraction of Lactobacillus Casei and Bifidobacterium Longum. J. Vet. Sci 2004, 41–48. [Google Scholar] [CrossRef]
  59. Rao, A.V.; Bested, A.C.; Beaulne, T.M.; Katzman, M.A.; Iorio, C.; Berardi, J.M.; Logan, A.C. A Randomized, Double-Blind, Placebo-Controlled Pilot Study of a Probiotic in Emotional Symptoms of Chronic Fatigue Syndrome. Gut Pathog 2009, 1. [Google Scholar] [CrossRef]
  60. Decout, A.; Krasias, I.; Roberts, L.; Gimeno Molina, B.; Charenton, C.; Brown Romero, D.; Tee, Q.Y.; Marchesi, J.R.; Ng, S.; Sykes, L.; et al. Lactobacillus Crispatus S-Layer Proteins Modulate Innate Immune Response and Inflammation in the Lower Female Reproductive Tract. bioRxiv 2024. [Google Scholar] [CrossRef]
  61. Ahire, J.J.; Sahoo, S.; Kashikar, M.S.; Heerekar, A.; Lakshmi, S.G.; Madempudi, R.S. In Vitro Assessment of Lactobacillus Crispatus UBLCp01, Lactobacillus Gasseri UBLG36, and Lactobacillus Johnsonii UBLJ01 as a Potential Vaginal Probiotic Candidate. Probiotics Antimicrob Proteins 2023, 15. [Google Scholar] [CrossRef]
  62. Argentini, C.; Fontana, F.; Alessandri, G.; Lugli, G.A.; Mancabelli, L.; Ossiprandi, M.C.; van Sinderen, D.; Ventura, M.; Milani, C.; Turroni, F. Evaluation of Modulatory Activities of Lactobacillus Crispatus Strains in the Context of the Vaginal Microbiota. Microbiol Spectr 2022, 10. [Google Scholar] [CrossRef] [PubMed]
  63. Tan, J.; Dong, L.; Jiang, Z.; Tan, L.; Luo, X.; Pei, G.; Qin, A.; Zhong, Z.; Liu, X.; Tang, Y.; et al. Probiotics Ameliorate IgA Nephropathy by Improving Gut Dysbiosis and Blunting NLRP3 Signaling. J Transl Med 2022, 20. [Google Scholar] [CrossRef] [PubMed]
  64. Mikelsaar, M.; Zilmer, M. Lactobacillus Fermentum ME-3—an Antimicrobial and Antioxidative Probiotic. Microb Ecol Health Dis 2009, 21, 1–27. [Google Scholar] [CrossRef] [PubMed]
  65. Mann, S.; Park, M.S.; Johnston, T. V.; Ji, G.E.; Hwang, K.T.; Ku, S. Oral Probiotic Activities and Biosafety of Lactobacillus Gasseri HHuMIN D. Microb Cell Fact 2021, 20. [Google Scholar] [CrossRef]
  66. Zheng, N.; Guo, R.; Wang, J.; Zhou, W.; Ling, Z. Contribution of Lactobacillus Iners to Vaginal Health and Diseases: A Systematic Review. Front Cell Infect Microbiol 2021, 11. [Google Scholar] [CrossRef]
  67. Villena, J.; Kitazawa, H. Modulation of Intestinal TLR4-Inflammatory Signaling Pathways by Probiotic Microorganisms: Lessons Learned from Lactobacillus Jensenii TL2937. Front Immunol 2014, 4. [Google Scholar] [CrossRef]
  68. Davoren, M.J.; Liu, J.; Castellanos, J.; Rodríguez-Malavé, N.I.; Schiestl, R.H. A Novel Probiotic, Lactobacillus Johnsonii 456, Resists Acid and Can Persist in the Human Gut beyond the Initial Ingestion Period. Gut Microbes 2019, 10, 458–480. [Google Scholar] [CrossRef]
  69. Van Gossum, A.; Dewit, O.; Louis, E.; De Hertogh, G.; Baert, F.; Fontaine, F.; Devos, M.; Enslen, M.; Paintin, M.; Franchimont, D. Multicenter Randomized-Controlled Clinical Trial of Probiotics (Lactobacillus Johnsonii, LA1) on Early Endoscopic Recurrence of Crohn’s Disease after Lleo-Caecal Resection. Inflamm Bowel Dis 2007, 13, 135–142. [Google Scholar] [CrossRef]
  70. Georgalaki, M.; Zoumpopoulou, G.; Anastasiou, R.; Kazou, M.; Tsakalidou, E. Lactobacillus Kefiranofaciens: From Isolation and Taxonomy to Probiotic Properties and Applications. Microorganisms 2021, Vol. 9, Page 2158 2021, 9, 2158. [Google Scholar] [CrossRef]
  71. Toumi, R.; Abdelouhab, K.; Rafa, H.; Soufli, I.; Raissi-Kerboua, D.; Djeraba, Z.; Touil-Boukoffa, C. Beneficial Role of the Probiotic Mixture Ultrabiotique on Maintaining the Integrity of Intestinal Mucosal Barrier in DSS-Induced Experimental Colitis. Immunopharmacol Immunotoxicol 2013, 35, 403–409. [Google Scholar] [CrossRef]
  72. Inchingolo, F.; Inchingolo, A.M.; Malcangi, G.; De Leonardis, N.; Sardano, R.; Pezzolla, C.; de Ruvo, E.; Di Venere, D.; Palermo, A.; Inchingolo, A.D.; et al. The Benefits of Probiotics on Oral Health: Systematic Review of the Literature. Pharmaceuticals (Basel) 2023, 16. [Google Scholar] [CrossRef] [PubMed]
  73. Chuang, L.C.; Huang, C.S.; Ou-Yang, L.W.; Lin, S.Y. Probiotic Lactobacillus Paracasei Effect on Cariogenic Bacterial Flora. Clin Oral Investig 2011, 15, 471–476. [Google Scholar] [CrossRef] [PubMed]
  74. Zhao, Y.; Dong, B.R.; Hao, Q. Probiotics for Preventing Acute Upper Respiratory Tract Infections. Cochrane Database Syst Rev 2022, 8. [Google Scholar] [CrossRef]
  75. Kabuki, T.; Saito, T.; Kawai, Y.; Uemura, J.; Itoh, T. Production, Purification and Characterization of Reutericin 6, a Bacteriocin with Lytic Activity Produced by Lactobacillus Reuteri LA6. Int J Food Microbiol 1997, 34, 145–156. [Google Scholar] [CrossRef]
  76. Schaefer, L.; Auchtung, T.A.; Hermans, K.E.; Whitehead, D.; Borhan, B.; Britton, R.A. The Antimicrobial Compound Reuterin (3-Hydroxypropionaldehyde) Induces Oxidative Stress via Interaction with Thiol Groups. Microbiology (Reading) 2010, 156, 1589–1599. [Google Scholar] [CrossRef]
  77. Bravo, J.A.; Forsythe, P.; Chew, M. V.; Escaravage, E.; Savignac, H.M.; Dinan, T.G.; Bienenstock, J.; Cryan, J.F. Ingestion of Lactobacillus Strain Regulates Emotional Behavior and Central GABA Receptor Expression in a Mouse via the Vagus Nerve. Proc Natl Acad Sci U S A 2011, 108, 16050–16055. [Google Scholar] [CrossRef] [PubMed]
  78. He, F.; Morita, H.; Ouwehand, A.C.; Hosoda, M.; Hiramatsu, M.; Kurisaki, J. ichi; Isolauri, E.; Benno, Y.; Salminen, S. Stimulation of the Secretion of Pro-Inflammatory Cytokines by Bifidobacterium Strains. Microbiol Immunol 2002, 46, 781–785. [Google Scholar] [CrossRef]
  79. Guo, Y.; Xie, J.P.; Deng, K.; Li, X.; Yuan, Y.; Xuan, Q.; Xie, J.; He, X.M.; Wang, Q.; Li, J.J.; et al. Prophylactic Effects of Bifidobacterium Adolescentis on Anxiety and Depression-Like Phenotypes After Chronic Stress: A Role of the Gut Microbiota-Inflammation Axis. Front Behav Neurosci 2019, 13. [Google Scholar] [CrossRef]
  80. Santana, S.I.; Silva, P.H.F.; Salvador, S.L.; Casarin, R.C.V.; Furlaneto, F.A.C.; Messora, M.R. Adjuvant Use of Multispecies Probiotic in the Treatment of Peri-Implant Mucositis: A Randomized Controlled Trial. J Clin Periodontol 2022, 49, 828–839. [Google Scholar] [CrossRef]
  81. Jeon, S.G.; Kayama, H.; Ueda, Y.; Takahashi, T.; Asahara, T.; Tsuji, H.; Tsuji, N.M.; Kiyono, H.; Ma, J.S.; Kusu, T.; et al. Probiotic Bifidobacterium Breve Induces IL-10-Producing Tr1 Cells in the Colon. PLoS Pathog 2012, 8, e1002714. [Google Scholar] [CrossRef]
  82. Xiao, J.; Katsumata, N.; Bernier, F.; Ohno, K.; Yamauchi, Y.; Odamaki, T.; Yoshikawa, K.; Ito, K.; Kaneko, T. Probiotic Bifidobacterium Breve in Improving Cognitive Functions of Older Adults with Suspected Mild Cognitive Impairment: A Randomized, Double-Blind, Placebo-Controlled Trial. J Alzheimers Dis 2020, 77, 139–147. [Google Scholar] [CrossRef] [PubMed]
  83. Turroni, F.; Duranti, S.; Milani, C.; Lugli, G.A.; van Sinderen, D.; Ventura, M. Bifidobacterium Bifidum: A Key Member of the Early Human Gut Microbiota. Microorganisms 2019, 7. [Google Scholar] [CrossRef] [PubMed]
  84. Zhao, L.; Xie, Q.; Etareri Evivie, S.; Liu, D.; Dong, J.; Ping, L.; Liu, F.; Li, B.; Huo, G. Bifidobacterium Dentium N8 with Potential Probiotic Characteristics Prevents LPS-Induced Intestinal Barrier Injury by Alleviating the Inflammatory Response and Regulating the Tight Junction in Caco-2 Cell Monolayers. Food Funct 2021, 12, 7171–7184. [Google Scholar] [CrossRef] [PubMed]
  85. Desbonnet, L.; Garrett, L.; Clarke, G.; Kiely, B.; Cryan, J.F.; Dinan, T.G. Effects of the Probiotic Bifidobacterium Infantis in the Maternal Separation Model of Depression. Neuroscience 2010, 170, 1179–1188. [Google Scholar] [CrossRef]
  86. Arunachalam, K.; Gill, H.S.; Chandra, R.K. Enhancement of Natural Immune Function by Dietary Consumption of Bifidobacterium Lactis (HN019). Eur J Clin Nutr 2000, 54, 263–267. [Google Scholar] [CrossRef]
  87. Sanders, M.E. Summary of Probiotic Activities of Bifidobacterium Lactis HN019. J Clin Gastroenterol 2006, 40, 776–783. [Google Scholar] [CrossRef]
  88. Haros, M.; Carlsson, N.G.; Almgren, A.; Larsson-Alminger, M.; Sandberg, A.S.; Andlid, T. Phytate Degradation by Human Gut Isolated Bifidobacterium Pseudocatenulatum ATCC27919 and Its Probiotic Potential. Int J Food Microbiol 2009, 135, 7–14. [Google Scholar] [CrossRef]
  89. Sun, Y.; Zhou, J.; Du, H.; Zhou, Z.; Han, Y.; Luo, M.; Guo, X.; Gu, M.; Yang, H.; Xiao, H. The Anti-Inflammatory Potential of a Strain of Probiotic Bifidobacterium Pseudocatenulatum G7: In Vitro and In Vivo Evidence. J Agric Food Chem 2024, 72, 10355–10365. [Google Scholar] [CrossRef]
  90. Sanchis-Chordà, J.; del Pulgar, E.M.G.; Carrasco-Luna, J.; Benítez-Páez, A.; Sanz, Y.; Codoñer-Franch, P. Bifidobacterium Pseudocatenulatum CECT 7765 Supplementation Improves Inflammatory Status in Insulin-Resistant Obese Children. Eur J Nutr 2019, 58, 2789–2800. [Google Scholar] [CrossRef]
  91. Zhao, Q.; Ren, H.; Yang, N.; Xia, X.; Chen, Q.; Zhou, D.; Liu, Z.; Chen, X.; Chen, Y.; Huang, W.; et al. Bifidobacterium Pseudocatenulatum-Mediated Bile Acid Metabolism to Prevent Rheumatoid Arthritis via the Gut-Joint Axis. Nutrients 2023, 15. [Google Scholar] [CrossRef]
  92. Mauricio, M.D.; Serna, E.; Fernández-Murga, M.L.; Portero, J.; Aldasoro, M.; Valles, S.L.; Sanz, Y.; Vila, J.M. Bifidobacterium Pseudocatenulatum CECT 7765 Supplementation Restores Altered Vascular Function in an Experimental Model of Obese Mice. Int J Med Sci 2017, 14, 444–451. [Google Scholar] [CrossRef]
  93. Tanner, S.A.; Chassard, C.; Rigozzi, E.; Lacroix, C.; Stevens, M.J.A. Bifidobacterium Thermophilum RBL67 Impacts on Growth and Virulence Gene Expression of Salmonella Enterica Subsp. Enterica Serovar Typhimurium. BMC Microbiol 2016, 16. [Google Scholar] [CrossRef] [PubMed]
  94. Nami, Y.; Bakhshayesh, R.V.; Jalaly, H.M.; Lotfi, H.; Eslami, S.; Hejazi, M.A. Probiotic Properties of Enterococcus Isolated from Artisanal Dairy Products. Front Microbiol 2019, 10, 426946. [Google Scholar] [CrossRef]
  95. Rivulgo, V.M.; Ceci, M.; Haeublein, G.E.; Sparo, M.D.; Sanchez Bruni, S.F. Efficacy of the Probiotic Strain Enterococcus Faecalis CECT7121 in Diarrhoea Prevention in Newborn Foals. 2018.
  96. Castro, M.S.; Molina, M.A.; Azpiroz, M.B.; Díaz, A.M.; Ponzio, R.; Sparo, M.D.; Manghi, M.A.; Canellada, A.M. Probiotic Activity of Enterococcus Faecalis CECT7121: Effects on Mucosal Immunity and Intestinal Epithelial Cells. J Appl Microbiol 2016, 121, 1117–1129. [Google Scholar] [CrossRef] [PubMed]
  97. Banwo, K.; Sanni, A.; Tan, H. Technological Properties and Probiotic Potential of Enterococcus Faecium Strains Isolated from Cow Milk. J Appl Microbiol 2013, 114, 229–241. [Google Scholar] [CrossRef]
  98. Watanabe, M.; Maruo, T.; Suzuki, T. Effects of Intake of Lactococcus Cremoris Subsp. Cremoris FC on Constipation Symptoms and Immune System in Healthy Participants with Mild Constipation: A Double-Blind, Placebo-Controlled Study. Int J Food Sci Nutr 2023, 74, 695–706. [Google Scholar] [CrossRef]
  99. Park, B.H.; Kim, I.S.; Park, J.K.; Zhi, Z.; Lee, H.M.; Kwon, O.W.; Lee, B.C. Probiotic Effect of Lactococcus Lactis Subsp. Cremoris RPG-HL-0136 on Intestinal Mucosal Immunity in Mice. Appl Biol Chem 2021, 64, 1–9. [Google Scholar] [CrossRef]
  100. Kimoto-Nira, H.; Mizumachi, K.; Nomura, M.; Kobayashi, M.; Fujita, Y.; Okamoto, T.; Suzuki, I.; Tsuji, N.M.; Kurisaki, J.I.; Ohmomo, S. Lactococcus Sp. as Potential Probiotic Lactic Acid Bacteria. Jpn Agric Res Q 2007, 41, 181–189. [Google Scholar] [CrossRef]
  101. Fusieger, A.; Martins, M.C.F.; de Freitas, R.; Nero, L.A.; de Carvalho, A.F. Technological Properties of Lactococcus Lactis Subsp. Lactis Bv. Diacetylactis Obtained from Dairy and Non-Dairy Niches. Braz J Microbiol 2020, 51, 313–321. [Google Scholar] [CrossRef]
  102. Fusieger, A.; Perin, L.M.; Teixeira, C.G.; de Carvalho, A.F.; Nero, L.A. The Ability of Lactococcus Lactis Subsp. Lactis Bv. Diacetylactis Strains in Producing Nisin. Antonie Van Leeuwenhoek 2020, 113, 651–662. [Google Scholar] [CrossRef]
  103. Vacca, C.; Contu, M.P.; Rossi, C.; Ferrando, M.L.; Blus, C.; Szmukler-Moncler, S.; Scano, A.; Orrù, G. In Vitro Interactions between Streptococcus Intermedius and Streptococcus Salivarius K12 on a Titanium Cylindrical Surface. Pathogens 2020, 9, 1–15. [Google Scholar] [CrossRef]
  104. Wescombe, P.A.; Hale, J.D.; Heng, N.C.; Tagg, J.R. Developing Oral Probiotics from Streptococcus Salivarius. Future Microbiol 2012, 7, 1355–1371. [Google Scholar] [CrossRef] [PubMed]
  105. Kekkonen, R.A.; Kajasto, E.; Miettinen, M.; Veckman, V.; Korpela, R.; Julkunen, I.; Kekkonen, R.A.; Kajasto, E.; Miettinen, M.; Veckman, V.; et al. Probiotic Leuconostoc Mesenteroides Ssp. Cremoris and Streptococcus Thermophilus Induce IL-12 and IFN-γ Production. World Journal of Gastroenterology 2008, Vol. 14, Pages: 1192--1203 2008, 14, 1192–1203. [Google Scholar] [CrossRef]
  106. Cousin, F.J.; Jouan-Lanhouet, S.; Théret, N.; Brenner, C.; Jouan, E.; Moigne-Muller, G. Le; Dimanche-Boitrel, M.T.; Jan, G. The Probiotic Propionibacterium Freudenreichii as a New Adjuvant for TRAIL-Based Therapy in Colorectal Cancer. Oncotarget 2016, 7, 7161. [Google Scholar] [CrossRef] [PubMed]
  107. Dyshlyuk, L.S.; Milentyeva, I.S.; Asyakina, L.K.; Ostroumov, L.A.; Osintsev, A.M.; Pozdnyakova, A. V. Using Bifidobacterium and Propionibacterium Strains in Probiotic Consortia to Normalize the Gastrointestinal Tract. Braz J Biol 2022, 84. [Google Scholar] [CrossRef]
  108. Shao, X.; Fang, K.; Medina, D.; Wan, J.; Lee, J.L.; Hong, S.H. The Probiotic, Leuconostoc Mesenteroides, Inhibits Listeria Monocytogenes Biofilm Formation. J Food Saf 2020, 40, e12750. [Google Scholar] [CrossRef]
  109. de Paula, A.T.; Jeronymo-Ceneviva, A.B.; Todorov, S.D.; Penna, A.L.B. The Two Faces of Leuconostoc Mesenteroides in Food Systems. Food Reviews International 2015, 31, 147–171. [Google Scholar] [CrossRef]
  110. Takata, K.; Kinoshita, M.; Okuno, T.; Moriya, M.; Kohda, T.; Honorat, J.A.; Sugimoto, T.; Kumanogoh, A.; Kayama, H.; Takeda, K.; et al. The Lactic Acid Bacterium Pediococcus Acidilactici Suppresses Autoimmune Encephalomyelitis by Inducing IL-10-Producing Regulatory T Cells. PLoS One 2011, 6. [Google Scholar] [CrossRef]
  111. Jiang, S.; Cai, L.; Lv, L.; Li, L. Pediococcus Pentosaceus, a Future Additive or Probiotic Candidate. Microb Cell Fact 2021, 20. [Google Scholar] [CrossRef]
  112. Song, D.; Ibrahim, S.; Hayek, S. Recent Application of Probiotics in Food and Agricultural Science. Probiotics 2012, 10, 1–34. [Google Scholar]
  113. Ross, R.P.; Fitzgerald, G.; Collins, K.; Stanton, C. Cheese Delivering Biocultures--Probiotic Cheese. Australian Journal of Dairy Technology, suppl. Proceedings Cheese Science 2002 2002, 57, 71. [Google Scholar]
  114. Lourens-Hattingh, A.; Viljoen, B.C. Yogurt as Probiotic Carrier Food. Int Dairy J 2001, 11, 1–17. [Google Scholar] [CrossRef]
  115. Yoon, K.Y.; Woodams, E.E.; Hang, Y.D. Production of Probiotic Cabbage Juice by Lactic Acid Bacteria. Bioresour Technol 2006, 97, 1427–1430. [Google Scholar] [CrossRef] [PubMed]
  116. Peres, C.M.; Peres, C.; Hernández-Mendoza, A.; Malcata, F.X. Review on Fermented Plant Materials as Carriers and Sources of Potentially Probiotic Lactic Acid Bacteria—With an Emphasis on Table Olives. Trends Food Sci Technol 2012, 26, 31–42. [Google Scholar] [CrossRef]
  117. Olatunde, O.O.; Obadina, A.O.; Omemu, A.M.; Oyewole, O.B.; Olugbile, A.; Olukomaiya, O.O. Screening and Molecular Identification of Potential Probiotic Lactic Acid Bacteria in Effluents Generated during Ogi Production. Ann Microbiol 2018, 68, 433–443. [Google Scholar] [CrossRef]
  118. Park, K.Y.; Jeong, J.K.; Lee, Y.E.; Daily, J.W. Health Benefits of Kimchi (Korean Fermented Vegetables) as a Probiotic Food. J Med Food 2014, 17, 6–20. [Google Scholar] [CrossRef]
  119. Udayakumar, S.; Rasika, D.M.D.; Priyashantha, H.; Vidanarachchi, J.K.; Ranadheera, C.S. Probiotics and Beneficial Microorganisms in Biopreservation of Plant-Based Foods and Beverages. Applied Sciences 2022, Vol. 12, Page 11737 2022, 12, 11737. [Google Scholar] [CrossRef]
  120. Vilela, A.; Cosme, F.; Inês, A. Wine and Non-Dairy Fermented Beverages: A Novel Source of Pro- and Prebiotics. Fermentation 2020, Vol. 6, Page 113 2020, 6, 113. [Google Scholar] [CrossRef]
  121. Esposito, E.; Iacono, A.; Bianco, G.; Autore, G.; Cuzzocrea, S.; Vajro, P.; Canani, R.B.; Calignano, A.; Raso, G.M.; Meli, R. Probiotics Reduce the Inflammatory Response Induced by a High-Fat Diet in the Liver of Young Rats. J Nutr 2009, 139, 905–911. [Google Scholar] [CrossRef]
  122. Zeng, M.Y.; Inohara, N.; Nuñez, G. Mechanisms of Inflammation-Driven Bacterial Dysbiosis in the Gut. Mucosal Immunol 2017, 10, 18–26. [Google Scholar] [CrossRef]
  123. Sepich-Poore, G.D.; Zitvogel, L.; Straussman, R.; Hasty, J.; Wargo, J.A.; Knight, R. The Microbiome and Human Cancer. Science 2021, 371. [Google Scholar] [CrossRef] [PubMed]
  124. Hill, D.A.; Siracusa, M.C.; Abt, M.C.; Kim, B.S.; Kobuley, D.; Kubo, M.; Kambayashi, T.; Larosa, D.F.; Renner, E.D.; Orange, J.S.; et al. Commensal Bacteria-Derived Signals Regulate Basophil Hematopoiesis and Allergic Inflammation. Nat Med 2012, 18, 538–546. [Google Scholar] [CrossRef]
  125. Caricilli, A.M.; Picardi, P.K.; de Abreu, L.L.; Ueno, M.; Prada, P.O.; Ropelle, E.R.; Hirabara, S.M.; Castoldi, Â.; Vieira, P.; Camara, N.O.S.; et al. Gut Microbiota Is a Key Modulator of Insulin Resistance in TLR 2 Knockout Mice. PLoS Biol 2011, 9. [Google Scholar] [CrossRef]
  126. Guo, S.; Al-Sadi, R.; Said, H.M.; Ma, T.Y. Lipopolysaccharide Causes an Increase in Intestinal Tight Junction Permeability in Vitro and in Vivo by Inducing Enterocyte Membrane Expression and Localization of TLR-4 and CD14. Am J Pathol 2013, 182, 375–387. [Google Scholar] [CrossRef] [PubMed]
  127. Kamada, N.; Seo, S.U.; Chen, G.Y.; Núñez, G. Role of the Gut Microbiota in Immunity and Inflammatory Disease. Nat Rev Immunol 2013, 13, 321–335. [Google Scholar] [CrossRef] [PubMed]
  128. Fallani, M.; Young, D.; Scott, J.; Norin, E.; Amarri, S.; Adam, R.; Aguilera, M.; Khanna, S.; Gil, A.; Edwards, C.A.; et al. Intestinal Microbiota of 6-Week-Old Infants across Europe: Geographic Influence beyond Delivery Mode, Breast-Feeding, and Antibiotics. J Pediatr Gastroenterol Nutr 2010, 51, 77–84. [Google Scholar] [CrossRef]
  129. Marcobal, A.; Barboza, M.; Froehlich, J.W.; Block, D.E.; German, J.B.; Lebrilla, C.B.; Mills, D.A. Consumption of Human Milk Oligosaccharides by Gut-Related Microbes. J Agric Food Chem 2010, 58, 5334–5340. [Google Scholar] [CrossRef]
  130. Malesza, I.J.; Malesza, M.; Walkowiak, J.; Mussin, N.; Walkowiak, D.; Aringazina, R.; Bartkowiak-Wieczorek, J.; Mądry, E. High-Fat, Western-Style Diet, Systemic Inflammation, and Gut Microbiota: A Narrative Review. Cells 2021, 10. [Google Scholar] [CrossRef]
  131. Zhang, C.; Zhang, M.; Pang, X.; Zhao, Y.; Wang, L.; Zhao, L. Structural Resilience of the Gut Microbiota in Adult Mice under High-Fat Dietary Perturbations. ISME J 2012, 6, 1848–1857. [Google Scholar] [CrossRef]
  132. Velázquez, K.T.; Enos, R.T.; Bader, J.E.; Sougiannis, A.T.; Carson, M.S.; Chatzistamou, I.; Carson, J.A.; Nagarkatti, P.S.; Nagarkatti, M.; Murphy, E.A. Prolonged High-Fat-Diet Feeding Promotes Non-Alcoholic Fatty Liver Disease and Alters Gut Microbiota in Mice. World J Hepatol 2019, 11, 619–637. [Google Scholar] [CrossRef]
  133. Bahar-Tokman, H.; Demirci, M.; Keskin, F.E.; Cagatay, P.; Taner, Z.; Ozturk-Bakar, Y.; Ozyazar, M.; Kiraz, N.; Kocazeybek, B.S. Firmicutes/Bacteroidetes Ratio in the Gut Microbiota and IL-1β, IL-6, IL-8, TLR2, TLR4, TLR5 Gene Expressions in Type 2 Diabetes. Clin Lab 2022, 68, 1903–1910. [Google Scholar] [CrossRef] [PubMed]
  134. Zimmer, J.; Lange, B.; Frick, J.S.; Sauer, H.; Zimmermann, K.; Schwiertz, A.; Rusch, K.; Klosterhalfen, S.; Enck, P. A Vegan or Vegetarian Diet Substantially Alters the Human Colonic Faecal Microbiota. European Journal of Clinical Nutrition 2012 66:1 2011, 66, 53–60. [Google Scholar] [CrossRef]
  135. Simões, C.D.; Maukonen, J.; Kaprio, J.; Rissanen, A.; Pietiläinen, K.H.; Saarela, M. Habitual Dietary Intake Is Associated with Stool Microbiota Composition in Monozygotic Twins. J Nutr 2013, 143, 417–423. [Google Scholar] [CrossRef] [PubMed]
  136. Ananthakrishnan, A.N. Epidemiology and Risk Factors for IBD. Nat Rev Gastroenterol Hepatol 2015, 12, 205–217. [Google Scholar] [CrossRef]
  137. Xia, B.; Crusius, J.B.A.; Meuwissen, S.G.M.; Peña, A.S. Inflammatory Bowel Disease: Definition, Epidemiology, Etiologic Aspects, and Immunogenetic Studies. World J Gastroenterol 1998, 4, 446–458. [Google Scholar] [CrossRef]
  138. Witthöft, T.; Eckmann, L.; Kim, J.M.; Kagnoff, M.F. Enteroinvasive Bacteria Directly Activate Expression of INOS and NO Production in Human Colon Epithelial Cells. Am J Physiol 1998, 275. [Google Scholar] [CrossRef] [PubMed]
  139. Kolios, G.; Valatas, V.; Ward, S.G. Nitric Oxide in Inflammatory Bowel Disease: A Universal Messenger in an Unsolved Puzzle. Immunology 2004, 113, 427–437. [Google Scholar] [CrossRef]
  140. Haneishi, Y.; Furuya, Y.; Hasegawa, M.; Picarelli, A.; Rossi, M.; Miyamoto, J. Inflammatory Bowel Diseases and Gut Microbiota. Int J Mol Sci 2023, 24. [Google Scholar] [CrossRef]
  141. Kabeerdoss, J.; Sankaran, V.; Pugazhendhi, S.; Ramakrishna, B.S. Clostridium Leptum Group Bacteria Abundance and Diversity in the Fecal Microbiota of Patients with Inflammatory Bowel Disease: A Case-Control Study in India. BMC Gastroenterol 2013, 13. [Google Scholar] [CrossRef]
  142. Plaza-Díaz, J.; Ruiz-Ojeda, F.J.; Vilchez-Padial, L.M.; Gil, A. Evidence of the Anti-Inflammatory Effects of Probiotics and Synbiotics in Intestinal Chronic Diseases. Nutrients 2017, 9. [Google Scholar] [CrossRef]
  143. Sood, A.; Midha, V.; Makharia, G.K.; Ahuja, V.; Singal, D.; Goswami, P.; Tandon, R.K. The Probiotic Preparation, VSL#3 Induces Remission in Patients with Mild-to-Moderately Active Ulcerative Colitis. Clin Gastroenterol Hepatol 2009, 7. [Google Scholar] [CrossRef]
  144. Wildt, S.; Nordgaard, I.; Hansen, U.; Brockmann, E.; Rumessen, J.J. A Randomised Double-Blind Placebo-Controlled Trial with Lactobacillus Acidophilus La-5 and Bifidobacterium Animalis Subsp. Lactis BB-12 for Maintenance of Remission in Ulcerative Colitis. J Crohns Colitis 2011, 5, 115–121. [Google Scholar] [CrossRef]
  145. Matsuoka, K.; Uemura, Y.; Kanai, T.; Kunisaki, R.; Suzuki, Y.; Yokoyama, K.; Yoshimura, N.; Hibi, T. Efficacy of Bifidobacterium Breve Fermented Milk in Maintaining Remission of Ulcerative Colitis. Dig Dis Sci 2018, 63, 1910–1919. [Google Scholar] [CrossRef]
  146. Pesce, M.; Seguella, L.; Del Re, A.; Lu, J.; Palenca, I.; Corpetti, C.; Rurgo, S.; Sanseverino, W.; Sarnelli, G.; Esposito, G. Next-Generation Probiotics for Inflammatory Bowel Disease. Int J Mol Sci 2022, 23. [Google Scholar] [CrossRef] [PubMed]
  147. Mimee, M.; Nadeau, P.; Hayward, A.; Carim, S.; Flanagan, S.; Jerger, L.; Collins, J.; McDonnell, S.; Swartwout, R.; Citorik, R.J.; et al. An Ingestible Bacterial-Electronic System to Monitor Gastrointestinal Health. Science 2018, 360, 915–918. [Google Scholar] [CrossRef]
  148. Ponziani, F.R.; Gerardi, V.; Gasbarrini, A. Diagnosis and Treatment of Small Intestinal Bacterial Overgrowth. Expert Rev Gastroenterol Hepatol 2016, 10, 215–227. [Google Scholar] [CrossRef]
  149. Zhong, C.; Qu, C.; Wang, B.; Liang, S.; Zeng, B. Probiotics for Preventing and Treating Small Intestinal Bacterial Overgrowth. J Clin Gastroenterol 2017, 51, 300–311. [Google Scholar] [CrossRef] [PubMed]
  150. Turnbaugh, P.J.; Ley, R.E.; Mahowald, M.A.; Magrini, V.; Mardis, E.R.; Gordon, J.I. An Obesity-Associated Gut Microbiome with Increased Capacity for Energy Harvest. Nature 2006, 444, 1027–1031. [Google Scholar] [CrossRef]
  151. Turnbaugh, P.J.; Ridaura, V.K.; Faith, J.J.; Rey, F.E.; Knight, R.; Gordon, J.I. The Effect of Diet on the Human Gut Microbiome: A Metagenomic Analysis in Humanized Gnotobiotic Mice. Sci Transl Med 2009, 1. [Google Scholar] [CrossRef]
  152. Ley, R.E.; Turnbaugh, P.J.; Klein, S.; Gordon, J.I. Microbial Ecology: Human Gut Microbes Associated with Obesity. Nature 2006, 444, 1022–1023. [Google Scholar] [CrossRef]
  153. Szulińska, M.; Łoniewski, I.; van Hemert, S.; Sobieska, M.; Bogdański, P. Dose-Dependent Effects of Multispecies Probiotic Supplementation on the Lipopolysaccharide (LPS) Level and Cardiometabolic Profile in Obese Postmenopausal Women: A 12-Week Randomized Clinical Trial. Nutrients 2018, 10. [Google Scholar] [CrossRef] [PubMed]
  154. Cani, P.D.; Amar, J.; Iglesias, M.A.; Poggi, M.; Knauf, C.; Bastelica, D.; Neyrinck, A.M.; Fava, F.; Tuohy, K.M.; Chabo, C.; et al. Metabolic Endotoxemia Initiates Obesity and Insulin Resistance. Diabetes 2007, 56, 1761–1772. [Google Scholar] [CrossRef] [PubMed]
  155. Creely, S.J.; McTernan, P.G.; Kusminski, C.M.; Fisher, F.M.; Da Silva, N.F.; Khanolkar, M.; Evans, M.; Harte, A.L.; Kumar, S. Lipopolysaccharide Activates an Innate Immune System Response in Human Adipose Tissue in Obesity and Type 2 Diabetes. Am J Physiol Endocrinol Metab 2007, 292. [Google Scholar] [CrossRef] [PubMed]
  156. Cani, P.D.; Delzenne, N.M. The Gut Microbiome as Therapeutic Target. Pharmacol Ther 2011, 130, 202–212. [Google Scholar] [CrossRef]
  157. Osterberg, K.L.; Boutagy, N.E.; McMillan, R.P.; Stevens, J.R.; Frisard, M.I.; Kavanaugh, J.W.; Davy, B.M.; Davy, K.P.; Hulver, M.W. Probiotic Supplementation Attenuates Increases in Body Mass and Fat Mass during High-Fat Diet in Healthy Young Adults. Obesity 2015, 23, 2364–2370. [Google Scholar] [CrossRef]
  158. Naito, E.; Yoshida, Y.; Makino, K.; Kounoshi, Y.; Kunihiro, S.; Takahashi, R.; Matsuzaki, T.; Miyazaki, K.; Ishikawa, F. Beneficial Effect of Oral Administration of Lactobacillus Casei Strain Shirota on Insulin Resistance in Diet-induced Obesity Mice. J Appl Microbiol 2011, 110, 650–657. [Google Scholar] [CrossRef]
  159. Shirvani-Rad, S.; Tabatabaei-Malazy, O.; Mohseni, S.; Hasani-Ranjbar, S.; Soroush, A.R.; Hoseini-Tavassol, Z.; Ejtahed, H.S.; Larijani, B. Probiotics as a Complementary Therapy for Management of Obesity: A Systematic Review. Evid Based Complement Alternat Med 2021, 2021, 6688450. [Google Scholar] [CrossRef]
  160. Ejtahed, H.S.; Mohtadi-Nia, J.; Homayouni-Rad, A.; Niafar, M.; Asghari-Jafarabadi, M.; Mofid, V.; Akbarian-Moghari, A. Effect of Probiotic Yogurt Containing Lactobacillus Acidophilus and Bifidobacterium Lactis on Lipid Profile in Individuals with Type 2 Diabetes Mellitus. J Dairy Sci 2011, 94, 3288–3294. [Google Scholar] [CrossRef]
  161. Hume, M.P.; Nicolucci, A.C.; Reimer, R.A. Prebiotic Supplementation Improves Appetite Control in Children with Overweight and Obesity: A Randomized Controlled Trial,, Am J Clin Nutr 2017, 105, 790–799. [Google Scholar] [CrossRef]
  162. Chambers, E.S.; Morrison, D.J.; Frost, G. Control of Appetite and Energy Intake by SCFA: What Are the Potential Underlying Mechanisms? Proc Nutr Soc 2015, 74, 328–336. [Google Scholar] [CrossRef]
  163. Dehghan, P.; Farhangi, M.A.; Tavakoli, F.; Aliasgarzadeh, A.; Akbari, A.M. Impact of Prebiotic Supplementation on T-Cell Subsets and Their Related Cytokines, Anthropometric Features and Blood Pressure in Patients with Type 2 Diabetes Mellitus: A Randomized Placebo-Controlled Trial. Complement Ther Med 2016, 24, 96–102. [Google Scholar] [CrossRef] [PubMed]
  164. Cryan, J.F.; O’riordan, K.J.; Cowan, C.S.M.; Sandhu, K. V.; Bastiaanssen, T.F.S.; Boehme, M.; Codagnone, M.G.; Cussotto, S.; Fulling, C.; Golubeva, A. V.; et al. The Microbiota-Gut-Brain Axis. Physiol Rev 2019, 99, 1877–2013. [Google Scholar] [CrossRef]
  165. Sharma, H.; Bajwa, J. Approach of Probiotics in Mental Health as a Psychobiotics. Arch Microbiol 2021, 204. [Google Scholar] [CrossRef] [PubMed]
  166. Misra, S.; Mohanty, D. Psychobiotics: A New Approach for Treating Mental Illness? Crit Rev Food Sci Nutr 2019, 59, 1230–1236. [Google Scholar] [CrossRef]
  167. Silva, Y.P.; Bernardi, A.; Frozza, R.L. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front Endocrinol (Lausanne) 2020, 11. [Google Scholar] [CrossRef]
  168. Chen, Y.; Xu, J.; Chen, Y. Regulation of Neurotransmitters by the Gut Microbiota and Effects on Cognition in Neurological Disorders. Nutrients 2021, 13. [Google Scholar] [CrossRef] [PubMed]
  169. Cani, P.D.; Osto, M.; Geurts, L.; Everard, A. Involvement of Gut Microbiota in the Development of Low-Grade Inflammation and Type 2 Diabetes Associated with Obesity. Gut Microbes 2012, 3. [Google Scholar] [CrossRef]
  170. Bercik, P.; Collins, S.M.; Verdu, E.F. Microbes and the Gut-Brain Axis. Neurogastroenterology & Motility 2012, 24, 405–413. [Google Scholar] [CrossRef]
  171. Luna, R.A.; Foster, J.A. Gut Brain Axis: Diet Microbiota Interactions and Implications for Modulation of Anxiety and Depression. Curr Opin Biotechnol 2015, 32, 35–41. [Google Scholar] [CrossRef]
  172. Wang, W.Y.; Tan, M.S.; Yu, J.T.; Tan, L. Role of Pro-Inflammatory Cytokines Released from Microglia in Alzheimer’s Disease. Ann Transl Med 2015, 3. [Google Scholar] [CrossRef]
  173. Kandpal, M.; Indari, O.; Baral, B.; Jakhmola, S.; Tiwari, D.; Bhandari, V.; Pandey, R.K.; Bala, K.; Sonawane, A.; Jha, H.C. Dysbiosis of Gut Microbiota from the Perspective of the Gut-Brain Axis: Role in the Provocation of Neurological Disorders. Metabolites 2022, 12. [Google Scholar] [CrossRef] [PubMed]
  174. Liu, J.; Wang, F.; Liu, S.; Du, J.; Hu, X.; Xiong, J.; Fang, R.; Chen, W.; Sun, J. Sodium Butyrate Exerts Protective Effect against Parkinson’s Disease in Mice via Stimulation of Glucagon like Peptide-1. J Neurol Sci 2017, 381, 176–181. [Google Scholar] [CrossRef]
  175. Wu, G.; Jiang, Z.; Pu, Y.; Chen, S.; Wang, T.; Wang, Y.; Xu, X.; Wang, S.; Jin, M.; Yao, Y.; et al. Serum Short-Chain Fatty Acids and Its Correlation with Motor and Non-Motor Symptoms in Parkinson’s Disease Patients. BMC Neurol 2022, 22. [Google Scholar] [CrossRef] [PubMed]
  176. Majumdar, A.; Siva Venkatesh, I.P.; Basu, A. Short-Chain Fatty Acids in the Microbiota-Gut-Brain Axis: Role in Neurodegenerative Disorders and Viral Infections. ACS Chem Neurosci 2023, 14, 1045–1062. [Google Scholar] [CrossRef]
  177. Cattaneo, A.; Cattane, N.; Galluzzi, S.; Provasi, S.; Lopizzo, N.; Festari, C.; Ferrari, C.; Guerra, U.P.; Paghera, B.; Muscio, C.; et al. Association of Brain Amyloidosis with Pro-Inflammatory Gut Bacterial Taxa and Peripheral Inflammation Markers in Cognitively Impaired Elderly. Neurobiol Aging 2017, 49, 60–68. [Google Scholar] [CrossRef] [PubMed]
  178. Zhu, M.; Liu, X.; Ye, Y.; Yan, X.; Cheng, Y.; Zhao, L.; Chen, F.; Ling, Z. Gut Microbiota: A Novel Therapeutic Target for Parkinson’s Disease. Front Immunol 2022, 13. [Google Scholar] [CrossRef]
  179. Nishiwaki, H.; Hamaguchi, T.; Ito, M.; Ishida, T.; Maeda, T.; Kashihara, K.; Tsuboi, Y.; Ueyama, J.; Shimamura, T.; Mori, H.; et al. Short-Chain Fatty Acid-Producing Gut Microbiota Is Decreased in Parkinson’s Disease but Not in Rapid-Eye-Movement Sleep Behavior Disorder. mSystems 2020, 5. [Google Scholar] [CrossRef]
  180. Dinan, T.G.; Stanton, C.; Cryan, J.F. Psychobiotics: A Novel Class of Psychotropic. Biol Psychiatry 2013, 74, 720–726. [Google Scholar] [CrossRef]
  181. Roy Sarkar, S.; Mitra Mazumder, P.; Banerjee, S. Probiotics Protect against Gut Dysbiosis Associated Decline in Learning and Memory. J Neuroimmunol 2020, 348. [Google Scholar] [CrossRef]
  182. Stolfi, C.; Maresca, C.; Monteleone, G.; Laudisi, F. Implication of Intestinal Barrier Dysfunction in Gut Dysbiosis and Diseases. Biomedicines 2022, 10, 289. [Google Scholar] [CrossRef]
  183. Tang, J.; Xu, L.; Zeng, Y.; Gong, F. Effect of Gut Microbiota on LPS-Induced Acute Lung Injury by Regulating the TLR4/NF-KB Signaling Pathway. Int Immunopharmacol 2021, 91. [Google Scholar] [CrossRef]
  184. Moon, C.; Baldridge, M.T.; Wallace, M.A.; Burnham, C.A.D.; Virgin, H.W.; Stappenbeck, T.S. Vertically Transmitted Faecal IgA Levels Determine Extra-Chromosomal Phenotypic Variation. Nature 2015, 521, 90–93. [Google Scholar] [CrossRef]
  185. Brandtzaeg, P. Secretory IgA: Designed for Anti-Microbial Defense. Front Immunol 2013, 4, 222. [Google Scholar] [CrossRef] [PubMed]
  186. Maldonado Galdeano, C.; Perdigón, G. The Probiotic Bacterium Lactobacillus Casei Induces Activation of the Gut Mucosal Immune System through Innate Immunity. Clin Vaccine Immunol 2006, 13, 219–226. [Google Scholar] [CrossRef]
  187. Link-Amster, H.; Rochat, F.; Saudan, K.Y.; Mignot, O.; Aeschlimann, J.M. Modulation of a Specific Humoral Immune Response and Changes in Intestinal Flora Mediated through Fermented Milk Intake. FEMS Immunol Med Microbiol 1994, 10, 55–63. [Google Scholar] [CrossRef] [PubMed]
  188. Marteau, P.; Vaerman, J.P.; Dehennin, J.P.; Bord, S.; Brassart, D.; Pochart, P.; Desjeux, J.F.; Rambaud, J.C. Effects of Intrajejunal Perfusion and Chronic Ingestion of Lactobacillus Johnsonii Strain La1 on Serum Concentrations and Jejunal Secretions of Immunoglobulins and Serum Proteins in Healthy Humans. Gastroenterol Clin Biol 1997, 21, 293–298. [Google Scholar] [PubMed]
  189. Paineau, D.; Carcano, D.; Leyer, G.; Darquy, S.; Alyanakian, M.A.; Simoneau, G.; Bergmann, J.F.; Brassart, D.; Bornet, F.; Ouwehand, A.C. Effects of Seven Potential Probiotic Strains on Specific Immune Responses in Healthy Adults: A Double-Blind, Randomized, Controlled Trial. FEMS Immunol Med Microbiol 2008, 53, 107–113. [Google Scholar] [CrossRef]
  190. Oliva, S.; Di Nardo, G.; Ferrari, F.; Mallardo, S.; Rossi, P.; Patrizi, G.; Cucchiara, S.; Stronati, L. Randomised Clinical Trial: The Effectiveness of Lactobacillus Reuteri ATCC 55730 Rectal Enema in Children with Active Distal Ulcerative Colitis. Aliment Pharmacol Ther 2012, 35, 327–334. [Google Scholar] [CrossRef]
Preprints 152806 g001
Figure 1. Detailed VOSViewer bibliographic analysis for the keywords “Probiotic” and “Gut microbiota” (database source: https://pubmed.ncbi.nlm.nih.gov/). Colours of nodes represent different clusters.
Figure 1. Detailed VOSViewer bibliographic analysis for the keywords “Probiotic” and “Gut microbiota” (database source: https://pubmed.ncbi.nlm.nih.gov/). Colours of nodes represent different clusters.
Preprints 152806 g001
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