March saw the publication of many excellent scientific publications related to different aspects of the microbiome. Here’s a 5-minute roundup of 5 recent papers worth knowing about.
A Weaning Reaction to Microbiota Is Required for Resistance to Immunopathologies in the Adult
Normally, the biggest dietary shift in a person’s life occurs in infancy when they are weaned:going from a milk diet to solid foods. This work from Eberllab of France used mice to look in detail at the gut microbiota and immune reactions to weaning. They found the gut microbiota reacted tothis dramatic dietary shift—and interestingly, the gut microbiota reaction kicked off an immune response that was necessary for the continued health of the animal into adulthood.
A Data Integration Multi-Omics Approach to Study Calorie Restriction-Induced Changes in Insulin Sensitivity[Open Access]
By now, scientists have dispelled the notion that there’s a gut microbiota composition typical of all obese individuals. But that doesn’t mean the gut microbiota has no relevance obesityin clinical settings. Some are investigating whether manipulation of gut microbiota or microbial metabolites might still be one way to go about treating the condition.
Along these lines, one of the first questions to ask is: can the success of dietary interventions for obesity sometimes be attributed to effects on the gut microbiota?This was recently addressed by a group that included The MICRO-Obes Consortium investigators. Knowing already that a calorie-restriction intervention induces positive changes in insulin sensitivity in those with obesity, the group comprehensively profiled individuals (n = 27) participating in this type of intervention to find the variables that appeared to contribute most to the beneficial changes. The top variables turned out to be 3 metagenomic species in the gut, as well as fiber intake.
Genetic effects on the commensal microbiota in inflammatory bowel disease patients[Open Access]
Thanks to severalgenome-wide association studies in inflammatory bowel disease (IBD), we have agoodidea of thegenetic variants that confer susceptibility to the condition. But how do genes and gut microbiota interact to set the stage for IBD?
The latest fascinating paper out of Sokol lab made links between genes and gut microbiota by studying associations between 4 IBD-related genetic variants and bacterial taxa in human IBD cases. They identified (and replicated) associations between NOD2 gene variants and both the Roseburia genus and Faecalibacterium prausnitzii, concluding that the IBD-related risk of some genetic variants is probably mediated, in part, by the gut microbiome. This may be good news for future disease prevention efforts, since the gut microbiome is, in theory, modifiable.
So far we know that genes and gluten intake are necessary for people to develop celiac disease (CD). Could gut bacteria beamong the environmental factors involved in the development of the disease?
The Canadian Verdu lab is building the case that specific small intestinal bacteria are involved in CD pathogenesis. In this paper, they focus on Pseudomonas aeruginosa, an opportunistic pathogen commonly found in the small intestines of those with CD. In mice with genetic risk factors for celiac-like disease, P. aeruginosa that produced the enzyme elastase induced immune activation and villi damage; but the same effects of P. aeruginosae lastase were not observed in mice without the genetic risk factors. The authors sum up their work by saying bacterial enzymes produced by some opportunistic pathogens can elicit immune responses, which may predispose a host to food sensitivity if the dietary environmental triggers are also present and the host’s genetic makeup is ‘permissive’ to that disease.
Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases
In linking gut microbiome features to disease, the determination of causality is always a key problem. Yes, we can move into animal models to look at mechanisms—but as this paper demonstrates nicely, we can also begin to infer microbiome-related causality using something called bidirectional Mendelian randomization analyses. These collaborators combined data from nearly 1000 individuals – genome-wide genotyping, gut metagenomic sequence data, and fecal short-chain fatty acid (SCFA) levels – and added this to information on genome-wide-associations for 17 metabolic and anthropometric traits. They asked whether human genetic predictors of gut microbiome features appeared to influence metabolic traits, and vice versa. Through this, they identified several potential causal relationships related to metabolic disease: for instance, between the SCFA propionate and type 2 diabetes.
