Antibiotics and dietary habits can affect the gut microbial community, thus influencing disease susceptibility. Although the effect of microbiota on the postnatal environment has been well documented, much less is known regarding the impact of gut microbiota at the embryonic stage. Here we show that maternal microbiota shapes the metabolic system of offspring in mice. During pregnancy, short-chain fatty acids produced by the maternal microbiota dictate the differentiation of neural, intestinal, and pancreatic cells through embryonic GPR41 and GPR43. This developmental process helps maintain postnatal energy homeostasis, as evidenced by the fact that offspring from germ-free mothers are highly susceptible to metabolic syndrome, even when reared under conventional conditions. Thus, our findings elaborate on a link between the maternal gut environment and the developmental origin of metabolic syndrome.

Centenarians, or individuals who have lived more than a century, represent the ultimate model of successful longevity associated with decreased susceptibility to ageing-associated illness and chronic inflammation [1][2][3] . The gut microbiota is considered to be a critical determinant of human health and longevity [4][5][6][7][8] . Here we show that centenarians (average 107 yo) have a distinct gut microbiome enriched in microbes capable of generating unique secondary bile acids, including iso-, 3-oxo-, and isoallo-lithocholic acid (LCA), as compared to elderly (85-89 yo) and young (21-55 yo) controls. Among these bile acids, the biosynthetic pathway for isoalloLCA had not been described previously. By screening 68 bacterial isolates from a centenarian's faecal microbiota, we identified Parabacteroides merdae and Odoribacteraceae strains as effective producers of isoalloLCA. Furthermore, we generated and tested mutant strains of P. merdae to show that the enzymes 5a-reductase (5AR) and 3bhydroxysteroid dehydrogenase (3bHSDH) were responsible for isoalloLCA production. This secondary bile acid derivative exerted the most potent antimicrobial effects among the tested bile acid compounds against gram-positive (but not gram-negative) multidrug-resistant pathogens, including Clostridioides difficile and vancomycin-resistant Enterococcus faecium.These findings suggest that specific bile acid metabolism may be involved in reducing the risk of pathobiont infection, thereby potentially contributing to longevity. MainThe microbiome has long been recognized as a key player in determining the health status of ageing individuals through its role in controlling digestive functions, bone density, neuronal activity, immunity, and resistance to pathogen infection [9][10][11][12][13] . Microbial consortia in elderly individuals often show increased interindividual variability and reduced diversity, and are thus being linked to immunosenescence, chronic systemic inflammation, and frailty 6,14 . An integrated understanding of the dynamic balance and functions of microbial members with respect to ageing is essential for establishing a strategy toward rational manipulation of the microbiota for restoring and/or maintaining tissue homeostasis and overall health.Centenarians (aged 100 years and older) are known to be less susceptible to age-related diseases including hypertension, diabetes, obesity, and cancer 3,15 . Moreover, centenarians have likely survived periods of hunger and several bouts with infectious diseases such as influenza, tuberculosis, shigellosis, and salmonellosis 16 . It has been postulated that there are centenarian-specific members of the gut microbiota which, rather than representing a mere consequence of ageing, might actively contribute to maintaining homeostasis, resilience, and healthful ageing [4][5][6]8 . In this study, we aimed

Gut microbiota mediates the effects of diet, thereby modifying host metabolism and the incidence of metabolic disorders. Increased consumption of omega-6 polyunsaturated fatty acid (PUFA) that is abundant in Western diet contributes to obesity and related diseases. Although gut-microbiota-related metabolic pathways of dietary PUFAs were recently elucidated, the effects on host physiological function remain unclear. Here, we demonstrate that gut microbiota confers host resistance to high-fat diet (HFD)-induced obesity by modulating dietary PUFAs metabolism. Supplementation of 10-hydroxy- cis -12-octadecenoic acid (HYA), an initial linoleic acid-related gut-microbial metabolite, attenuates HFD-induced obesity in mice without eliciting arachidonic acid-mediated adipose inflammation and by improving metabolic condition via free fatty acid receptors. Moreover, Lactobacillus -colonized mice show similar effects with elevated HYA levels. Our findings illustrate the interplay between gut microbiota and host energy metabolism via the metabolites of dietary omega-6-FAs thereby shedding light on the prevention and treatment of metabolic disorders by targeting gut microbial metabolites.