Restoring low-fiber diets-induced Lachnospiraceae bacterium loss partially recovers fiber digestion and immune function in mammals

Mammals rely on their gut microbiota to degrade cellulose, the major component of dietary fiber. Westernized populations harbor a depleted microbiome with reduced fiber-digesting capacity and impaired immune regulation due to prolonged consumption of low-fiber diets. Comparable patterns are evident in other mammals, including Western commercial pigs raised on high-energy, low-fiber diets, exhibiting reduced diversity and abundance of fiber-degrading bacteria. In contrast, semi-free-ranging Chinese indigenous pigs consuming fiber-rich diets retain a more diverse and functionally resilient microbiota, reflecting divergent trajectories of host-microbiota co-evolution. However, the specific cellulose-degrading species lost and strategies to restore these functions remain unclear in mammals. By analyzing 473 human stool metagenomes spanning non-westernized and westernized diets, together with 251 fecal 16S rRNA datasets and 95 metagenomes from Western commercial pigs, Chinese indigenous pigs, and their crossbred progeny, we identified the Lachnospiraceae bacterium as a key symbiont enriched in non-westernized guts. This bacterium possesses an extensive Carbohydrate-Active Enzymes repertoire conferring strong fiber-degrading capacity. Notably, low-fiber diets leave a genetic signature on this keystone gut symbiont, which cannot be reversed by short-term dietary interventions alone. Reintroduction of Lachnospiraceae bacterium to germ-free mice improved feed efficiency and increased acetic acid production. Intestinal transcriptomics and peripheral blood flow cytometry revealed that it activates a broad adaptive immune response, promoting CD4 + T cell accumulation, B cell activation, and anti-inflammatory cytokine induction. Reintroduction of this bacterium also alleviated dextran sodium sulfate-induced colitis. These findings highlight the preclinical functional potential of this Lachnospiraceae bacterium in mitigating low-fiber diets-induced dysfunction in mammals. • Lachnospiraceae bacterium is lost in the gut following exposure to low-fiber diets • Short-term dietary interventions fail to rescue Lachnospiraceae bacterium loss • Lachnospiraceae bacterium has fiber-degrading and anti-inflammatory abilities • Restored Lachnospiraceae bacterium rebuilds fiber digestion and immune homeostasis • Lachnospiraceae bacterium counters low-fiber diet disorders as probiotic