Biology subjects

Greter, G.

Publications and source records attributed to Greter, G..

3 recordsLinked to original sources

bioRxiv2023

Acute targeted induction of gut-microbial metabolism disrupts host circadian rhythm

The gut microbiota and host diurnal rhythm mutually influence each other, and microbiota metabolism has been shown to play a role in regulating host circadian function via secretion of fermentation products. Microbial metabolism is dependent on the availability of nutrients for the microbiota, typically through the hosts food intake, making it challenging to disentangle the effect of host and microbiota metabolism. In this study, we acutely induced gut microbial metabolic activity without inducing host metabolism in mice. We found that increasing microbial metabolism in the gut altered clock gene expression locally. Actuating microbiota metabolism also reduced host food intake beyond the calories provided by the microbiota, suggesting a systemic signaling effect of microbial metabolism on the host.

microbiology↗

bioRxiv2022

Fitness advantage of Bacteroides thetaiotaomicron capsular polysaccharide is dependent on the resident microbiota

Many microbiota-based therapeutics rely on our ability to introduce a microbe of choice into an already-colonized intestine. However, we remain largely blind to the quantitative effects of processes determining colonization success. In this study, we used genetically-barcoded Bacteroides thetaiotaomicron (B.theta) strains in combination with mathematical modeling to quantify population bottlenecks experienced by B.theta during gut colonization. Integrating population bottlenecks sizes with careful quantification of net growth rates in vivo and in vitro allows us to build models describing the events during intestinal colonization in the context of gnotobiotic and complex microbiotas. Using these models, we estimated the decrease in niche size for B.theta colonization with increasing microbiota complexity. In addition, our system can be applied to mechanistically dissect colonization defects of mutant strains. As a proof of concept, we demonstrated that the competitive disadvantage of a B.theta mutant lacking capsular polysaccharide is due to a combination of an increased lag-phase before growth initiation in the gut, combined with an increased clearance rate. Crucially, the requirement for the B.theta capsule depended strongly on microbiota composition, suggesting that the dominant role may be protection from bacterial or phage aggression rather than from host-induced bactericidal mechanisms.

microbiology↗

bioRxiv2022

Non-invasive monitoring of microbiota and host metabolism using Secondary electrospray ionization-Mass spectrometry

The metabolic "handshake" between the microbiota and its mammalian host is a complex, dynamic process with potentially major influences on health. Dissecting the interaction between microbial species/strains and metabolites found in host tissues has been a challenge due to the high diversity of a complete micro-biota and the requirement for invasive sampling, which precludes high-resolution longitudinal analysis. Here we demonstrate that secondary electrospray ionization mass spectrometry can be used to non-invasively monitor metabolic activity of the intestinal microbiome of a live, awake mouse. This was achieved via analysis of the headspace volatile and semi-volatile metabolome of individual gut microbiota bacterial species growing in pure culture, as well as from live gnotobiotic mice specifically colonized with these microbes (i.e. metabolites released to the atmosphere via breath, the skin and from the gut). The microbial origin of these compounds was confirmed by feeding of heavy-isotope labeled microbiota-accessible sugars. This reveals that the microbiota is a major contributor to the released metabolites of a whole live mouse, and that it is possible to capture the catabolism of sugars and cross-feeding within the gut microbiota of a living animal using volatile/semi-volatile metabolite monitoring.

systems biology↗