Blautia wexlerae promotes compensatory postnatal growth and alleviates gut inflammation via beta-alanine synthesis from dietary xylan in low birthweight individuals

Low birthweight (LBW) and the associated postnatal growth retardation present significant health challenges, yet effective nutrition-based interventions remain limited. Using a LBW piglet model, we identified impaired dietary fiber utilization and heightened gut inflammation in piglets with growth failure, in contrast to those exhibiting compensatory growth. These phenotypes could be recapitulated in mice following fecal microbiota transplantation (FMT). Notably, Blautia wexlerae emerged as a key fiber-degrading bacterium enriched in both LBW piglets showing catch-up growth and FMT-recipient mice. Consistently, B. wexlerae was also significantly enriched in LBW children who demonstrated compensatory growth (P < 0.001). Administration of B. wexlerae indeed promoted growth in both mice and LBW piglets and further mitigated DSS-induced colitis in mice, in a xylan-dependent manner. Mechanistically, B. wexlerae metabolized dietary xylan to produce beta-alanine through the bacterial beta-alanine pathway, which subsequently inhibited G-protein-coupled receptor 84 (Gpr84) on macrophages in the intestinal tract. This inhibition in turn enhanced mucosal barrier integrity, reduced inflammation, and facilitated growth. Collectively, our findings highlight the critical role of B. wexlerae in postnatal growth and identify novel dietary intervention strategies to improve healthy growth and development of LBW individuals.