Early life establishment of site-specific microbial communities in the gut

Abstract

Fecal sampling is widely utilized to define small intestinal tissue-level microbial communities in healthy and diseased newborns. However, this approach may lead to inaccurate assessments of disease or therapeutics in newborns because of the assumption that the taxa in the fecal microbiota are representative of the taxa present throughout the gastrointestinal tract. To assess the stratification of microbes in the newborn gut and to evaluate the probable shortcoming of fecal sampling in place of tissue sampling, we simultaneously compared intestinal mucosa and fecal microbial communities in 15 neonates undergoing intestinal resections. We report three key results. First, when the site of fecal and mucosal samples are further apart, their microbial communities are more distinct, as indicated by low mean Sørensen similarity indices for each patient's fecal and tissue microbiota. Second, two distinct niches (intestinal mucosa and fecal microbiota) are evident by principal component analyses, demonstrating the critical role of sample source in defining microbial composition. Finally, in contrast to adult studies, intestinal bacterial diversity was higher in tissue than in fecal samples. This study represents an unprecedented map of the infant microbiota from intestinal mucosa and establishes discernable biogeography throughout the neonatal gastrointestinal tract. Our results question the reliance on fecal microbiota as a proxy for the developing intestinal microbiota. Additionally, the robust intestinal tissue-level bacterial diversity we detected at these early ages may contribute to the maturation of mucosal immunity.

Keywords: :

• neonatal microbiome
• host-microbial interactions
• fecal microbiome
• intestinal bacterial diversity
• mucosal immunity

10.4161/gmic.28442

Disclosure of Potential Conflicts of Interest

No potential conflict of interest was disclosed.

Acknowledgments

We express our appreciation for the patients and their families who were willing to participate in this study. We thank the Vanderbilt Departments of Pediatric Surgery and Pathology for their efforts with patient recruitment and sample collection. We are grateful to J Aschner and A Stark for discussion and critical review of this manuscript. This project was supported by the American Academy of Pediatrics Marshall Klaus Perinatal Research Award (to J.R.K.) and the Eunice Kennedy Shriver National Institute Of Child Health and Human Development (NICHD) grants T32HD068256 (to J.R.K.) and K08HD061607 (to J.H.W.), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grant K08DK090146 (to D.J.M.), and the National Science Foundation grant DEB-1046149 (to S.R.B.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NICHD, NIDDK, or the National Institutes of Health (NIH). This project was also funded by the Vanderbilt Digestive Disease Research Center Grant P30DK058404, Vanderbilt Diabetes Center Grant P30DK20593 (both NIDDK and NIH), and the Vanderbilt CTSA Grant UL1 RR024975-01 from the National Center for Research Resources (NCRR and NIH).