Phascolarctobacterium faecium retunes the dialogue between macrophages and group 1 innate lymphoid cells to intercept obesity development in mice

The global obesity epidemic demands a deeper understanding of causal mechanisms and accessible solutions. Here, we surveyed 7,569 human metagenomes, showing that the symbiont Phascolarctobacterium faecium is more prevalent in non-obese adults regardless of nationality, sex, or age. In obese mice fed P. faecium DSM 32890 we confirmed the specificity of its anti-obesogenic properties compared to other species of the same genus. Independently of the viability, P. faecium DSM 32890 activated alternative macrophages, which buffered the obesity-induced increase in gut-resident ILC1s and triggered defense mechanisms (sIgA, antimicrobial peptides, and interleukin 22) and Tregs, ultimately mitigating glucose intolerance and body weight gain. The metabolic benefits remained in the absence of the adaptive immune system but were lost by administering an inhibitor of alternative macrophage polarization. We prove that P. faecium DSM 32890 intercepts the intestinal inflammatory cell circuity, patrolled by macrophages and seconded by IlC1s, protecting against obesity and metabolic comorbidities.