Our results support the hypothesis that metformin shifts gut microbiota composition through the enrichment of mucin-degrading A. muciniphila as well as several SCFA-producing microbiota. Future studies are needed to determine if these shifts mediate metformin's glycemic and anti-inflammatory properties.

Fiber fermentation by gut microbiota yields short-chain fatty acids (SCFAs) that are either absorbed by the gut or excreted in feces. Studies are conflicting as to whether SCFAs are beneficial or detrimental to cardiometabolic health, and how gut microbiota associated with SCFAs is unclear. In this study of 441 community-dwelling adults, we examined associations of fecal SCFAs, gut microbiota diversity and composition, gut permeability, and cardiometabolic outcomes, including obesity and hypertension. We assessed fecal microbiota by 16S rRNA gene sequencing, and SCFA concentrations by gas chromatography/mass spectrometry. Fecal SCFA concentrations were inversely associated with microbiota diversity, and 70 unique microbial taxa were differentially associated with at least one SCFA (acetate, butyrate or propionate). Higher SCFA concentrations were associated with a measure of gut permeability, markers of metabolic dysregulation, obesity and hypertension. Microbial diversity showed association with these outcomes in the opposite direction. Associations were significant after adjusting for measured confounders. In conclusion, higher SCFA excretion was associated with evidence of gut dysbiosis, gut permeability, excess adiposity, and cardiometabolic risk factors. Studies assessing both fecal and circulating SCFAs are needed to test the hypothesis that the association of higher fecal SCFAs with obesity and cardiometabolic dysregulation is due to less efficient SCFA absorption.

Tuberculosis associates with a wide spectrum of disease outcomes. The Beijing (Bj) lineage of Mycobacterium tuberculosis (Mtb) is suggested to be more virulent than other Mtb lineages and prone to elicit non-protective immune responses. However, highly heterogeneous immune responses were reported upon infection of innate immune cells with Bj strains or stimulation with their glycolipids. Using both in vitro and in vivo mouse models of infection, we here report that the molecular mechanism for this heterogeneity may be related to distinct TLR activations. Among this Mtb lineage, we found strains that preferentially activate TLR2, and others that also activate TLR4. Recognition of Mtb strains by TLR4 resulted in a distinct cytokine profile in vitro and in vivo, with specific production of type I IFN. We also uncover a novel protective role for TLR4 activation in vivo. Thus, our findings contribute to the knowledge of the molecular basis underlying how host innate immune cells handle different Mtb strains, in particular the intricate host-pathogen interaction with strains of the Mtb Bj lineage.

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Westernization and its accompanying epidemiological transitions are associated with changes in gut microbiota. While the extremes of this lifestyle spectrum have been compared (hunter-gatherers, industrialized countries), populations undergoing such shifts have received little attention. To fill the gap of knowledge about the microbiome evolution following broad lifestyle changes and the emergence of disease-associated dysbiosis, we performed a cross-sectional study in which we characterized the microbiota of 441 Colombian adults through 16S rRNA gene sequencing and determined its relationship with demographic, health-related and dietary parameters. We showed that in the gut microbiota of this cohort thrive taxa proper of both hunter-gatherers (Prevotella, Treponema) and citizens of industrialized countries (Bacteroides, Bifidobacterium, Barnesiella); the relative abundances of these taxa differed from those in Western and non-Western populations. We also showed that the Colombian gut microbiota is composed of five consortia of co-abundant microorganisms that are differentially associated with lifestyle, obesity and cardiometabolic disease, and highlighted metabolic pathways that might explain associations between microbiota and host health. Our results give insights into the evolution of the gut microbiota, and underscore the importance of this community to human health. Promoting the growth of specific microbial consortia could help ameliorating physiological conditions associated with Western lifestyles.

The incorporation of cardiometabolic data allows a refined identification of dissimilarities in the gut microbiota; within a given BMI category, marker taxa associated with obesity and cardiometabolic disease are exacerbated in individuals with abnormal health status. Our results highlight the importance of the detailed assessment and classification of individuals that should be carried out prior to the evaluation of obesity treatments targeting the gut microbiota.