Faecalibacterium prausnitzii Induces an Anti-inflammatory Response and a Metabolic Reprogramming in Human Monocytes.

BACKGROUND & AIMS: Faecalibacterium prausnitzii, a highly abundant gut bacterium, has been linked to overall health, and is decreased in several pathologic conditions, such as inflammatory bowel disease (IBD). F prausnitzii has shown anti-inflammatory properties in human and mouse models, notably through the induction of interleukin 10 (IL10) signaling. Here, we investigated which cell types from human blood and intestinal tissue are responsible for producing IL10 induced by F prausnitzii and provide the first mechanistic insights. METHODS: Immune cells isolated from human blood and intestinal lamina propria of IBD patients and noninflamed controls, were stimulated with F prausnitzii EXL01 strain, Coprococcus comes 27758 strain, and Escherichia coli MG1655 strain, with or without lipopolysaccharide (LPS), and analyzed by LEGENDplex, enzyme-linked immunosorbent assay, flow cytometry, RNA sequencing, and Seahorse technology. RESULTS: F prausnitzii induced a direct and dose-dependent production of IL10 in cluster of differentiation 14(+) monocytes from the systemic circulation and intestinal tissue, without inducing a proinflammatory response compared with LPS stimulation. RNA sequencing and Seahorse analyses corroborated these results, revealing that F prausnitzii affects cellular energy metabolism in healthy and inflammatory conditions, in a different way from 2 other tested bacteria and LPS. The anti-inflammatory response induced by F prausnitzii in monocytes was dependent on mitochondrial respiration. CONCLUSIONS: F prausnitzii induces an anti-inflammatory response and rewires energy metabolism in human monocytes in healthy and inflamed conditions, potentially explaining its beneficial impact on intestinal inflammation and human health in general. These results provide new insight into the mechanisms underlying the anti-inflammatory effects of F prausnitzii and are crucial for a better understanding of its potential use in IBD treatment.