ARTICLE | doi:10.20944/preprints202308.0761.v1
Subject: Biology And Life Sciences, Animal Science, Veterinary Science And Zoology Keywords: protease; microbiome; intestine; pig; poultry; virulence
Online: 9 August 2023 (14:33:48 CEST)
Exogenous proteases are well established for hydrolysing proteins and improving the digestibility of amino acids, which, in animal production, enhances growth performance and diet formulation flexibility. Attention has now turned to the wider, or ‘extra-proteinaceous’, benefits of proteases. Both host and (gut) microbiome utilise amino acids for diverse functions beyond just cellular growth and proliferation. For example, the host produces a diverse array of proteinaceous secretions that seek to modulate the activity of the intestinal microbiome and opportunities to interact with host (e.g., epithelial) receptors. Reciprocally, the microbiome utilises various protein-based components to perform individual lifestyle traits, such as colonising gut niches, production of virulence traits, etc., which can be influenced by protease activity and amino acid availability. In addition, microbial fermentation of proteins and amino acids produces metabolites that may be considered undesirable (e.g., toxic) for the host’s cells or, for example, can act as signalling molecules, shaping the secretion of gut hormones and function. Parallels may also exist between various antibiotic growth promoters and proteases, in that both can target/impact microbial proteins (synthesis and degradation, respectively). There are many aspects to consider, such as determining optimal intestinal levels and spectra of proteolytic activity under various scenarios, but great potential exists.
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: probiotic; pig; poultry; microbiota; microbiome; intestine
Online: 19 November 2020 (10:26:23 CET)
The intestinal microbiota and its functions are regarded as critical for host health and disease. Probiotics can influence the gut microbiome and its interactions with the host, and are currently defined as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host”. Probiotics have become common components of strategies to promote livestock health, welfare and productivity, not least due to restrictions on the use of antimicrobial drugs. Common probiotic organisms are considered commensals and are ‘generally recognized as safe’ (GRAS) via oral administration. This review outlines potential probiotic mechanisms, including recent findings. These mechanisms include those interactions primarily occurring between the supplemented probiotic microorganisms and the indigenous intestinal microbiota, perhaps within the gut lumen, as well as more direct interactions with the host via mucosal receptors or more distally following absorption of microbial components. There is good evidence that the gut microbiome is relatively stable in ‘healthy’ individuals and resistant to ‘colonisation’ by exogenous microbes, which helps exclude pathogens, but has implications for the establishment of probiotics, and could increase the importance of microbe-microbe interactions. However, such microbiomes may be receptive to complementary microbes or functions, while supplemented probiotics may dominate luminal populations, particularly in less populated regions of the intestine. Moreover, host-adapted microbes or microbiomes may elicit different host responses and/or be more effective. Some considerations for the interpretation of study results, including extrapolation from different models or microbial strains, are also included. In addition, notable mechanistic and/or pathogen challenge studies from pigs and poultry are highlighted to underline the recognised potential of probiotics in these species, particularly as the appropriate selection of microorganisms and their application continues to be better understood and improve.
ARTICLE | doi:10.20944/preprints202307.1410.v1
Subject: Biology And Life Sciences, Food Science And Technology Keywords: mantle tissue; novel toxin; scallop; small intestine
Online: 20 July 2023 (10:22:45 CEST)
We previously showed that feeding mice a diet containing 1% mantle tissue decreased food consumption, leading to death. We also isolated and identified toxic substances in the mantle tissue. In the present study, we investigated the characteristics and stability of mantle tissue toxicity. Treatment of mantle tissue with 1 mM HCl, 1 mM NaOH, 1 mM dithiothreitol, and 1 mM H2O2 and heating did not reduce the toxicity of mantle tissue in mice. These results suggest that mantle toxins are stable in tissues, particularly when exposed to acidic and digestive enzymes. We examined whether mantle tissue exhibited acute toxicity. Diets containing 1% and 20% mantle extract showed similar levels of toxicity, demonstrating that feeding of mantle tissue does not lead to acute toxicity. Finally, we examined the toxicity of the mantle tissue against small intestinal tissue. Chronic feeding of mantle tissue to mice changed the color of the small intestine. Real-time PCR analysis showed that mantle tissue feeding caused changes of inflammation and endoplasmic reticulum stress markers in the small intestine. These results suggest that feeding of mantle tissue causes toxicity after causing initial damage to the small intestinal tissue.
ARTICLE | doi:10.20944/preprints202008.0120.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: intestine microbiota; Cattle Egret; Pied Crows; Kinshasa
Online: 5 August 2020 (09:59:45 CEST)
Purpose: Our study focused on Pied Grow and Cattle Egret, two commensal and ubiquitous birds feeding in dumps and frequenting our homes. Our aim was to identify the bacteria that birds bring to our homes and could be a potential risk to Congolese health. Method: We have done bacteriological analyses of bird feces for to explore its gut micriobiota composition. The feces were collected in the uricotelic cloaca by using a swab in 52 Cattle Egrets (Bubulcus ibis) and 23 Pied Crows (Corvus albus) from Kinshasa city. Results: Bacteriological analyses revealed the presence of Proteus vulgaris (3.8%) and Klebsiella pneumoniae (5.8%) on Cattle Egret, Salmonella sp. (8.7%), Klebsiella pneumoniae (8.7%), Pseudomonas aeruginosa (21.7%), Proteus vulgaris (30.4%) on Pied Crow, Citrobacter spp and Escherichia coli (100%) on both Cattle Egret and Pied Crow respectively. Conclusion: The presence of these pathogenic germs, suggesting these commensal and ubiquitous birds may be potential vectors of various Diseases which pose serious health problems in the region.
ARTICLE | doi:10.20944/preprints201803.0051.v1
Subject: Biology And Life Sciences, Food Science And Technology Keywords: glutamine; perioperative period; bypass surgery; intestine surgery; HPLC
Online: 7 March 2018 (05:21:29 CET)
Glutamine is the main amino acid which is substrate for gluconeogenesis in postoperative period. It is suggested that this leads to a substantial and a long-term decline in glutamine concentration. Glutamine is a source of energy for the synthesis of nucleotides, lymphocytes and cells of gastrointestinal tract. In this study, 79 patients were qualified to a coronary artery bypass surgery (Group I) or a surgery in the large intestine area (Group II). The objectives of this study were: evaluation of the impact of surgical procedures on the serum concentration of glutamine of the operated patients, assessment of gender, weight and BMI impact on glutamine concentration and analysis of the correlation between glutaminę serum concentration and laboratory parameters. The mean concentration of glutamine before surgery, the 3rd and 5th day after surgery was higher in Group I. CRP level in the 3rd and 5th postoperative day was higher in Group II. There were no significant differences betweengroups when it comes to BMI and the concentration of CRP (p <0.05). Glutamine concentration depends on the severity of inflammation, the operated body cavity and the intensified catabolism which results from different pathophysiology of digestive system diseases and coronary arterial disease.
ARTICLE | doi:10.20944/preprints202112.0120.v1
Subject: Biology And Life Sciences, Endocrinology And Metabolism Keywords: aging; NMR spectroscopy; mice; energy metabolism; fat; intestine; metabolomics
Online: 8 December 2021 (12:03:07 CET)
Energy metabolism, including alterations in energy intake and expenditure, is closely related to aging and longevity. Metabolomics studies have recently unraveled changes in metabolite composition in plasma and tissues during aging and have provided critical information to elucidate the molecular basis of aging process. However, the metabolic changes in tissues responsible for food intake and lipid storage have remained unexplored. In this study, we aimed to investigate aging-related metabolic alterations in these tissues. To fill this gap, we employed NMR-based metabolomics in several tissues, including different parts of the intestine (duodenum, jejunum, ileum) and brown/white adipose tissues (BAT, WAT) of young (9-10 weeks) and old (96-104 weeks) wild-type (mixed genetic background of 129/J and C57BL/6) mice. We further included plasma and skeletal muscle of the same mice to verify previous results. Strikingly, we found that duodenum, jejunum, ileum, and WAT do not metabolically age. In contrast, plasma, skeletal muscle, and BAT show a strong metabolic aging phenotype. Overall, we provide first insights into the metabolic changes of tissues essential for nutrient uptake and lipid storage and have identified biomarkers for metabolites that could be further explored to study the molecular mechanisms of aging.
ARTICLE | doi:10.20944/preprints202308.1998.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: ADME; drug transport; jejunum; small intestine; differentiation; 2D cell culture
Online: 30 August 2023 (09:49:39 CEST)
Still, the most common in vitro model for absorption, distribution, metabolism and excretion (ADME) purposes is the Caco-2 cell line. However, clear differences in gene- and protein expression towards the small intestine and an at best fair prediction accuracy of intestinal drug absorption restrict the usefulness as model for intestinal epithelial cells. To overcome these limitations, we evaluated a panel of low-passaged patient-derived colorectal cancer cell lines of the HROC collection concerning similarities to small intestinal epithelial cells and their potential to predict intestinal drug absorption. After initial screen of a larger panel, ten cell lines with confluent outgrowth and long-lasting barrier forming potential were further characterized in close detail. Tight junctional complexes and microvilli structures were detected in all lines, differentiated epithelial cells were abundant in 7/10. All lines expressed multiple transporter molecules, with expression levels in three lines being close to those of small intestinal epithelial cells. Compared to the Caco-2 model, three HROC lines demonstrated both higher similarity to jejunal epithelial tissue cells and higher regulatory potential of relevant drug transporters. In sum, these lines would be better suited human small intestinal epithelium models for basic and translational research; especially for ADME studies.
ARTICLE | doi:10.20944/preprints202306.0149.v1
Subject: Medicine And Pharmacology, Dentistry And Oral Surgery Keywords: Cytokines; Intestine; Rats; Periodontitis; Dextran Sulphate Sodium; Inflammatory Bowel Diseases
Online: 2 June 2023 (07:43:24 CEST)
Our research aimed to explore how resolving periodontal inflammation impacts cytokine expression in the colon of aged Wistar rats. Animal studies have been used to investigate the two-way relationship between periodontitis and Inflammatory Bowel Disease (IBD), where chronic inflammation in either the mouth or intestines can negatively affect the other. We allocated sixteen male Wistar rats, aged between 8-11 months, into four groups: (1) Ligature-induced periodontitis (LIP) without the resolution of periodontal inflammation (RPI) (LIP; n=4), (2) LIP + RPI (n=4), (3) LIP + DSS-induced colitis (DIC) without RPI (n=4), and LIP+DIC+RPI (n=5). We performed histopathological and immunological analyses on the periodontal and intestinal tissues and analysed cytokine expressions using a Rat Cytokine 23-Plex Immunoassay. Our findings showed that animals with and without DIC who underwent RPI showed significantly lower levels of IL-2, IL-4, IL-5, IL-10, IL-13, IL-17, IL-18, and TNF-α in the intestine compared to those without treatment. The RPI effectively reduced the number of inflammatory cells in the lamina propria and restored the epithelial barrier in the intestine in animals with DIC. The resolution of periodontal inflammation significantly reduced the levels of pro-inflammatory cytokines and chemokines in the intestine of aged rats with and without DSS-induced colitis.
ARTICLE | doi:10.20944/preprints202310.0733.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: liver; intestine-liver axis; innate immune genes; comparative genomics; IL-2
Online: 12 October 2023 (02:30:26 CEST)
The liver is not only a digestive gland, but also an immune tissue that receives a double infusion from the hepatic artery and the hepatic portal vein. Receiving 80% of its blood supply from the intestine through the hepatic portal vein system, the liver is enriched with a large number of innate immune cells, which carry out the process of immune response by detecting pathogens entering the organism through the intestine. The intestine and liver communicate extensively through the bile ducts, portal vein and the somatic circulation, a bidirectional communication known as the intestinal-liver axis. The mammalian gut is considered an important microbial ecosystem. The interplay between the natural immune system and microbes coordinates the physiology of the whole organism, and in specific mammalian lineages, there is a dependency between the host and its associated microbes. To this end, we explored the regulatory mechanisms of natural immunity genes at the genome-wide level. Based on comparative genomics, 1473 bovine natural immunity genes were obtained by collecting the latest reports of human natural immunity genes and updated bovine genomic data for comparison, and a bovine natural immunity gene database was initially constructed to screen and match calf liver natural immunity differential genes mainly affected by the phylum Mimosoidea and the phylum Thick-walled Bacteria, and 16 differentially expressed natural immunity genes were obtained. In addition, the results of IPA analysis indicated that the upstream factor IL-2 initiated the PI3K/AKt/mTOR, mitogen-activated protein kinase (MAPK) pathway and JAK/STAT5 pathway, leading to the liver's involvement in gut microbial immune regulation.
ARTICLE | doi:10.20944/preprints202208.0159.v1
Subject: Biology And Life Sciences, Endocrinology And Metabolism Keywords: metabolomics; NMR; PEMT; knockout; aging; mice; liver; intestine; white/brown adipose tissue
Online: 8 August 2022 (13:36:04 CEST)
Phospholipid metabolism, including phosphatidylcholine (PC) biosynthesis, is crucial for various biological functions and is associated to longevity. Phosphatidylethanolamine N-methyltransferase (PEMT) is a protein that catalyzes the biosynthesis of PC, the levels of which change in various organs such as brain and kidney during aging. However, the role of PEMT for systemic PC supply is not fully understood. To address how PEMT affects aging-associated energy metabolism in tissues responsible for nutrient absorption, lipid storage and energy consumption, we employed NMR-based metabolomics to study liver, plasma, intestine (duodenum, jejunum, ileum), brown/white adipose tissues (BAT, WAT), and skeletal muscle of young (9–10 weeks) and old (96–104 weeks) wild-type (WT) and PEMT knockout (KO) mice. We found that the effect of PEMT-knockout was tissue-specific and age-dependent. Deficiency of PEMT affected the metabolome of all tissues examined, among which the metabolome of BAT from both young and aged KO mice was dramatically changed in comparison to WT mice, whereas the metabolome of jejunum was only slightly affected. As for aging, the absence of PEMT increased the divergence of metabolome during aging of liver, WAT, duodenum and ileum and decreased the impact on skeletal muscle. Overall, our results suggest that PEMT plays a previously unexplored critical role in both aging and energy metabolism.
Subject: Biology And Life Sciences, Food Science And Technology Keywords: Iron, Zinc, Interactions, DMT1, ZIP4, Pancreas, Metabolism, Homeostasis, Intestine, Caco-2 cells
Online: 9 July 2019 (14:32:11 CEST)
Iron and zinc are essential micronutrients required for growth and health. Deficiencies of these nutrients are highly prevalent among populations, but can be alleviated by supplementation. Cross-sectional studies in humans showed positive association of serum zinc levels with hemoglobin and markers of iron status. Dietary restriction of zinc or intestinal specific conditional knock out of ZIP4 (SLC39A4), an intestinal zinc transporter, in experimental animals demonstrated iron deficiency anemia and tissue iron accumulation. Similarly increased iron accumulation has been observed in cultured cells exposed to zinc deficient media. These results together suggest a potential role of zinc in modulating whole body iron metabolism. Studies in intestinal cell culture models demonstrate that zinc induces iron uptake and transcellular transport via induction of divalent metal iron transporter-1 (DMT1) and ferroportin (FPN) expression, respectively. It is interesting to note that intestinal cells are exposed to very high levels of zinc through pancreatic secretions, which is a major route of zinc excretion from the body. Therefore, zinc appears to be modulating the iron metabolism possibly via regulating the DMT1 and FPN1 levels. Herein we critically reviewed the available evidence to hypothesize novel mechanism of Zinc-DMT1/FPN axis in regulating intestinal iron absorption and tissue iron accumulation to facilitate future research aimed at understanding the yet elusive mechanisms of iron and zinc interactions.
ARTICLE | doi:10.20944/preprints202307.1300.v1
Subject: Biology And Life Sciences, Animal Science, Veterinary Science And Zoology Keywords: taurine; weaned piglets; antioxidant capacity; Intestine Healthy; microorganism; growth performance; Nrf2/ARE signaling pathway
Online: 19 July 2023 (09:56:00 CEST)
Early weaning of piglets caused excessive concentration of free radicals, which would oxidize and damage the intestinal tract of piglets, resulting in dyspepsia, low growth, diarrhea, microbiota disorders and intestinal infections. This research studied on effect of different levels of taurine in diets on intestinal oxidative damage in early weaned piglets. A total of 48 weaned piglets (6.71 ± 0.73 kg) of 28-day-old crossbred "Duroc × Landrace × Yorkshire" were assigned to 4 groups with 12 replicates per group and 1 pig per replicate: piglets were fed a basal diet with 0.0% (CON), 0.2% taurine (L-Tau), 0.3% taurine (M-Tau), or 0.4% taurine (H-Tau). The animal experiment lasted for 30 days. With the increase of dietary taurine dosage, the activity of antioxidant enzymes including superoxide dismutase（SOD）,glutathione peroxidase（GPX）,catalase（CAT） and peroxidase（POD） were up-regulated (Linear, P < 0.05), the mRNA abundance of antioxidant enzymes including SOD1, SOD2, GPX1 and heme oxygenase-1（HO-1）were up-regulated (P < 0.05), glutathione (GSH) concentrations was up-regulated (Linear, P < 0.05) , nitric oxide (NO), malondialdehyde (MDA) and oxidized glutathione (GSSG) concentrations were down-regulated (Linear, P < 0.05);The villus height (VH) and villus height/ crypt depth (VH/CD) of jejunum and ileum were increased (Linear, P < 0.05); The expression of tight junction proteins including zonula occludens protein 1(ZO-1), occludin (OCLN) and closure protein 1(CLDN-1) in the jejunum mucosa were up-regulated (Linear, P < 0.05), the mRNA abundance of ZO-1, OCLN and CLDN-1 were up-regulated (P < 0.05),and the D-lactose (D-LA) content in blood was down-regulated (Linear, P < 0.05); the colonization abundance of Firmicutes was increased (Linear, P < 0.05), while Proteobacteria and Spirochaetota was decreased (Linear, P < 0.05); The diarrhea index decreased (Linear, P < 0.05), while the feed conversion rate increased (Linear, P < 0.05). Collectively, supplementation of 0.3% and 0.4% taurine in feed can significantly alleviate intestinal oxidative damage by enhancing antioxidant capacity of piglets, and improve feed utilization of piglets after repairing intestinal damage.
REVIEW | doi:10.20944/preprints202305.1184.v1
Subject: Biology And Life Sciences, Cell And Developmental Biology Keywords: cell biology; gene expression; adipose tissue; bone; cartilage; intestine; kidney; liver; lung; pancreas; skin
Online: 17 May 2023 (04:41:00 CEST)
Parathyroid-hormone-related protein (PTHrP) is encoded by PTHLH gene which, by alternative promoter usage and splicing mechanisms, can give rise to at least three isoforms of 139, 141 and 173 amino acids with distinct C-terminals. PTHrP is subjected to different post-translational processing that generates smaller bioactive forms, comprising amino terminus, midregion (containing a nuclear/nucleolar targeting signal) and carboxy terminus peptides. Both the full-length protein and the discrete peptides are key controllers of viability, proliferation, differentiation and apoptosis in diverse normal and pathological biological systems via the reprogramming of gene expression and remodulation of PKA or PKC-mediated signalization mechanisms. The aim of this review is to pick up selected studies on PTHrP-associated signatures as revealed by molecular profiling assays, focusing on the available data about exemplary differentiating, differentiated or non-tumoral cell and tissue models. In particular, the data presented relate to adipose, bone, dental, cartilaginous and skin tissues, and also intestinal, renal, hepatic, pulmonary and pancreatic epithelia, with a focus on hepatic fibrosis-, pancreatitis- and diabetes-related changes as diseased states. Whether reported, the biochemical and/or physiological aspects associated with the specific molecular modulation of gene expression and signal transduction pathways in the target model systems under examination will be also briefly commented.
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: low intensity exercise; intestine; sodium-dependent glucose transporter; glucose transporter 2; glucagon like peptide 2
Online: 20 April 2021 (11:48:02 CEST)
Exercise affects various organs. However, its effects on nutrient digestion and absorption in the intestinal tract are not well understood. A few studies have reported that exercise training in-creases the expression of carbohydrate digestion and absorption molecules. Exercise was also shown to increase the concentration of blood glucagon like peptide-2(GLP-2), which regulates carbohydrate digestion and absorption in small intestinal epithelium. Therefore, we investigated the effects of exercise on intestinal digestion and absorption molecules and the levels of GLP-2. 6-wk-old of male mice were divided into 2 groups; sedentary (SED) and low-intensity exercise (LEx). LEx mice were required to run on a treadmill (12.5 m/min, 60 min), whereas SED mice rested. All mice were euthanized 1 h after exercise or rest and plasma, jejunum, ileum, and colon were sampled. Samples were analyzed using EIA and immunoblotting. The levels of plasma GLP-2 and the expression of the GLP-2 receptor, sucrase-isomaltase (SI), and glucose transporter (GLUT2) in the jejunum were increased in LEx group. We showed that acute low-intensity exer-cise affects the intestinal carbohydrate digestion and absorption molecules via GLP-2. Our results suggest that exercise might provide new benefits to the small intestine for people with intestinal frailty.
ARTICLE | doi:10.20944/preprints202004.0198.v1
Subject: Medicine And Pharmacology, Gastroenterology And Hepatology Keywords: mathematical modelling; peristalsis; smoothed particle hydrodynamics (SPH); fluid dynamics; large intestine; colonl proximal colon; fluid-structure interactions; drug delivery
Online: 12 April 2020 (15:57:17 CEST)
The proximal part of the colon offers opportunities to prolong the absorption window following oral administration of a drug. In this work, we used computer simulations to understand how the hydrodynamics in the proximal colon might affect the release from dosage forms designed to target the colon. For this purpose, we developed and compared three different models: a completely-filled colon, a partially-filled colon and a partially-filled colon with a gaseous phase present (gas-liquid model).The highest velocities of the liquid were found in the completely-filled model, which also shows the best mixing profile, defined by the distribution of tracking particles over time. No significant differences with regard to the mixing and velocity profiles were found between the partially-filled model and the gas-liquid model. The fastest transit time of an undissolved tablet was found in the completely-filled model. The velocities of the liquid in the gas-liquid model are slightly higher along the colon than in the partially-filled model. The filling level has an impact on the exsisting shear forces and shear rates, which are decisive factors in the development of new drugs and formulations.
REVIEW | doi:10.20944/preprints202305.0034.v1
Subject: Biology And Life Sciences, Cell And Developmental Biology Keywords: organ-on-a-chip; gut-on-a-chip; intestine; in vitro; ex vivo; ADME; oral bioavailability; drug development; microbiome; IBD
Online: 2 May 2023 (01:15:08 CEST)
The gut plays a key role in drug absorption and metabolism of orally ingested drugs. Additionally, characterization of intestinal disease processes are increasingly gaining more attention as gut health is an important contributor to our overall health. The most recent innovation to study intestinal processes in vitro is the development of gut-on-a-chip (GOC) systems. Compared to conventional in vitro models they offer more translational value, and many different GOC models have been presented over the past years. Here, we reflect on the almost unlimited choices in designing and selecting a GOC for preclinical drug (or food) development research. Four components that largely influence the GOC design are highlighted, namely 1) the biological research questions, 2) chip fabrication and materials, 3) tissue engineering, and 4) the environmental and biochemical cues to add or measure in the GOC. Examples are presented of GOC studies in the two major areas of preclinical intestinal research: 1) intestinal absorption and metabolism to study the oral bioavailability of compounds, and 2) treatment-orientated research for intestinal diseases. The last section of this review presents an outlook on the limitations to overcome in order to accelerate preclinical GOC research.
HYPOTHESIS | doi:10.20944/preprints202004.0153.v1
Subject: Biology And Life Sciences, Virology Keywords: Severe acute respiratory syndrome coronavirus 2; 2019-nCoV; COVID-19; angiotensin converting enzyme 2; Receptor; Live Attenuated Oral Vaccine; Intestine; proximal and distal enterocytes; herd immunity
Online: 9 April 2020 (13:10:50 CEST)
Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2/2019-nCoV) infection is an emerging pandemic. The virus binds to angiotensin converting enzyme 2 (ACE2) and TMPRSS2 which are abundantly expressed on various human cells including lung epithelial cells and intestinal cells and the virus can infect these cells. Currently no specific treatments or vaccines are available for this disease. A per oral live attenuated vaccine can be beneficial in SARS-Cov-2 infection because the attenuated virus initially infects the gut, stimulates the mucosa associated immune system sparing the respiratory system during the initial immune response. The live virus can also spread in the community boosting herd immunity.