TY - JOUR
T1 - Maternal Lactobacillus reuteri supplementation shifts the intestinal microbiome in mice and provides protection from experimental colitis in female offspring
AU - Krishna, Mahesh
AU - Engevik, Melinda
AU - Queliza, Karen
AU - Britto, Savini
AU - Shah, Rajesh
AU - Ruan, Wenly
AU - Wang, Hongtao
AU - Versalovic, James
AU - Kellermayer, Richard
N1 - Funding Information:
The authors thank the Gutsy Kids Fund, including philanthropic leadership from the Brock Wagner family and donation from the Frugoni and other generous families (to RK); the Klaasmeyer family funds for PSC research (to RK); and the Crohn’s and Colitis Foundation ProKiids Network (for grant/research time support to RK). Additionally, the Alkek Center for Metagenomics and Microbiome Research at Baylor College of Medicine was very helpful in aiding microbiome data analysis. Bridget Stroup was also essential with her support of statistical analysis as well as critical review of the revised manuscript.
Publisher Copyright:
© 2021 The Authors. FASEB BioAdvances published by The Federation of American Societies for Experimental Biology.
PY - 2022/2
Y1 - 2022/2
N2 - The purpose of our experiment was to explore how stochastic (inter-individual variation) gut microbiome composition may link to inflammatory bowel disease (IBD) susceptibility and guide the development of a perinatal preventative probiotic. Dextran sodium sulfate (DSS) was introduced to C57BL/BJ mice to induce acute colitis as a model of IBD. Potentially protective bacteria were identified using a discovery-validation cohort approach toward stochastic DSS susceptibility. Lactobacilli (two different cocktails of L. reuteri and L. johnsonii strains) or control media were supplemented by mouth to dams prior to delivery and during lactation (i.e., perinatal probiotic). The pups were evaluated for DSS susceptibility at young adulthood. Fecal Lactobacillus was increased in the DSS-resistant mice in both the discovery and validation cohorts. Maternal supplementation of female offspring with an L. reuteri cocktail (strains 6798-1, 6798-jm, and 6798-cm) induced progressive microbiome separation and protection against colitis by young adulthood. Maternal supplementation of L. reuteri could confer protection against DSS colitis in young adult female mice. This work is the first to exploit stochastic mammalian microbiome variation to guide microbial therapeutic identification. Our findings underscore neonatal microbiome plasticity and set the stage for the potential development of perinatally deliverable protective probiotics against human IBD.
AB - The purpose of our experiment was to explore how stochastic (inter-individual variation) gut microbiome composition may link to inflammatory bowel disease (IBD) susceptibility and guide the development of a perinatal preventative probiotic. Dextran sodium sulfate (DSS) was introduced to C57BL/BJ mice to induce acute colitis as a model of IBD. Potentially protective bacteria were identified using a discovery-validation cohort approach toward stochastic DSS susceptibility. Lactobacilli (two different cocktails of L. reuteri and L. johnsonii strains) or control media were supplemented by mouth to dams prior to delivery and during lactation (i.e., perinatal probiotic). The pups were evaluated for DSS susceptibility at young adulthood. Fecal Lactobacillus was increased in the DSS-resistant mice in both the discovery and validation cohorts. Maternal supplementation of female offspring with an L. reuteri cocktail (strains 6798-1, 6798-jm, and 6798-cm) induced progressive microbiome separation and protection against colitis by young adulthood. Maternal supplementation of L. reuteri could confer protection against DSS colitis in young adult female mice. This work is the first to exploit stochastic mammalian microbiome variation to guide microbial therapeutic identification. Our findings underscore neonatal microbiome plasticity and set the stage for the potential development of perinatally deliverable protective probiotics against human IBD.
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U2 - 10.1096/fba.2021-00078
DO - 10.1096/fba.2021-00078
M3 - Article
AN - SCOPUS:85118351030
SN - 2573-9832
VL - 4
SP - 109
EP - 120
JO - FASEB BioAdvances
JF - FASEB BioAdvances
IS - 2
ER -