Host-compound foraging by intestinal microbiota revealed by single-cell stable isotope probing

Abstract

The animal and human intestinal mucosa secretes an assortment of compounds to establish a physical barrier between the host tissue and intestinal contents, a separation that is vital for health. Some pathogenic microorganisms as well as members of the commensal intestinal microbiota have been shown to be able to break down these secreted compounds. Our understanding of host-compound degradation by the commensal microbiota has been limited to knowledge about simplified model systems because of the difficulty in studying the complex intestinal ecosystem in vivo. In this study, we introduce an approach that overcomes previous technical limitations and allows us to observe which microbial cells in the intestine use host-derived compounds. We added stable isotopelabeled threonine i.v. to mice and combined fluorescence in situ hybridization with high-resolution secondary ion mass spectrometry imaging to characterize utilization of host proteins by individual bacterial cells. We show that two bacterial species, Bacteroides acidifaciens and Akkermansia muciniphila, are important hostprotein foragers in vivo. Using gnotobiotic mice we show that microbiota composition determines the magnitude and pattern of foraging by these organisms, demonstrating that a complex microbiota is necessary in order for this niche to be fully exploited. These results underscore the importance of in vivo studies of intestinal microbiota, and the approach presented in this study will be a powerful tool to address many other key questions in animal and human microbiome research.nanoSIMS | stable isotope probing

Host adaptive immunity alters gut microbiota

“…The Gram-negative bacterium A. muciniphila has been recently found to be enriched following antibiotics treatment (Dubourg et al, 2013;Hansen et al, 2013) and have the capability to control inflammation (Everard et al, 2013). Initially considered as a host mucin-degrading bacterium, A. muciniphila was found to colonize the mouse gut without consuming much host-derived compounds (Berry et al, 2013). Although the physiological function of this bacterium in immunocompromised hosts is still unclear, our results suggest that A. muciniphila may be used as a biomarker for immunodeficiency.…”

Diets that differ in their FODMAP content alter the colonic luminal microenvironment

“…Simplistically, such bacteria are able to adhere to mucus and feed off glycans and mucin proteins as part of the mucus secreted by the gut epithelium 29. Extensive degradation of the mucous layer might be detrimental by impairing gut barrier function.…”

Tracking heavy water (D 2 O) incorporation for identifying and sorting active microbial cells

“…Both B. acidifaciens and A. muciniphila were stimulated by mucin. These two species are known to degrade mucin in pure cultures (76,77) and are important host-compound degraders in vivo (68). A. muciniphila has a phosphotransferase transporter system that is likely capable of taking up a range of simple sugars, including glucose, glucosamine, and mannose (78).…”