PreprintArticleVersion 1Preserved in Portico This version is not peer-reviewed
Vertical Transfer of Maternal Gut Microbes to Offspring of Western Diet-Fed Dams Drives Reduced Levels of Tryptophan Metabolites and Postnatal Innate Immune Response
Version 1
: Received: 10 May 2024 / Approved: 13 May 2024 / Online: 13 May 2024 (13:28:01 CEST)
How to cite:
Sugino, K. Y.; Janssen, R. C.; McMahan, R. H.; Zimmerman, C.; Friedman, J. E.; Jonscher, K. R. Vertical Transfer of Maternal Gut Microbes to Offspring of Western Diet-Fed Dams Drives Reduced Levels of Tryptophan Metabolites and Postnatal Innate Immune Response. Preprints2024, 2024050842. https://doi.org/10.20944/preprints202405.0842.v1
Sugino, K. Y.; Janssen, R. C.; McMahan, R. H.; Zimmerman, C.; Friedman, J. E.; Jonscher, K. R. Vertical Transfer of Maternal Gut Microbes to Offspring of Western Diet-Fed Dams Drives Reduced Levels of Tryptophan Metabolites and Postnatal Innate Immune Response. Preprints 2024, 2024050842. https://doi.org/10.20944/preprints202405.0842.v1
Sugino, K. Y.; Janssen, R. C.; McMahan, R. H.; Zimmerman, C.; Friedman, J. E.; Jonscher, K. R. Vertical Transfer of Maternal Gut Microbes to Offspring of Western Diet-Fed Dams Drives Reduced Levels of Tryptophan Metabolites and Postnatal Innate Immune Response. Preprints2024, 2024050842. https://doi.org/10.20944/preprints202405.0842.v1
APA Style
Sugino, K. Y., Janssen, R. C., McMahan, R. H., Zimmerman, C., Friedman, J. E., & Jonscher, K. R. (2024). Vertical Transfer of Maternal Gut Microbes to Offspring of Western Diet-Fed Dams Drives Reduced Levels of Tryptophan Metabolites and Postnatal Innate Immune Response. Preprints. https://doi.org/10.20944/preprints202405.0842.v1
Chicago/Turabian Style
Sugino, K. Y., Jacob E Friedman and Karen R Jonscher. 2024 "Vertical Transfer of Maternal Gut Microbes to Offspring of Western Diet-Fed Dams Drives Reduced Levels of Tryptophan Metabolites and Postnatal Innate Immune Response" Preprints. https://doi.org/10.20944/preprints202405.0842.v1
Abstract
Maternal obesity and/or Western diet (WD) is associated with increased risk of metabolic dysfunction-associated steatotic liver disease (MASLD) in offspring, driven, in part, by dysregulation of the early life microbiome. Here, using a mouse model of WD-induced maternal obesity, we demonstrate that exposure to a disordered microbiome from WD-fed dams suppressed circulating levels of endogenous ligands of the aryl hydrocarbon receptor (AHR; indole, indole-3-acetate) and TMAO (a product of AHR-mediated transcription), as well as hepatic expression of Il10 (an AHR target), in offspring at 3 weeks of age. This signature was recapitulated by fecal microbial transfer from WD-fed pregnant dams to chow-fed germ-free (GF) lactating dams following parturition, and was associated with reduced abundance of Lactobacillus in GF offspring. Further, expression of Il10 was downregulated in liver myeloid cells and in LPS-stimulated bone marrow-derived macrophages (BMDM) in adult offspring, suggestive of a hypo-responsive, or tolerant, innate immune response. BMDMs from adult mice lacking AHR in macrophages exhibited a similar tolerogenic response, including diminished expression of Il10. Overall, our study shows that exposure to maternal WD alters microbial metabolites in the offspring that affect AHR signaling, potentially contributing to innate immune hypo-responsiveness and progression of MASLD, and highlights the impact of early life gut dysbiosis on offspring metabolism. Further investigations are warranted to elucidate the complex interplay between maternal diet, gut microbial function, and development of neonatal innate immune tolerance and potential therapeutic interventions targeting these pathways.
Biology and Life Sciences, Immunology and Microbiology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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