ArticleCell2026
Oxygen-responsive bacterial glycosphingolipid links symbiont fitness and immune development in neonatal host.
Article in Cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Symbiotic gut bacteria must re-establish themselves in every host generation, yet the molecular strategies enabling this inheritance remain poorly understood. Here, we show that Bacteroides fragilis uses a membrane glycolipid, alpha-galactosylceramide (BfaGC), to colonize the neonatal gut. Genome-wide fitness profiling revealed that BfaGC biosynthesis is selectively required during early life, when transient oxygenation creates a physiological bottleneck for strict anaerobes. Mechanistically, BfaGC reduces membrane proton permeability, sustaining the proton-motive force that supports aerobic respiration. This oxygen-responsive adaptation simultaneously generates a host-facing immunomodulatory signal that calibrates neonatal natural killer T (NKT) cell development, linking bacterial fitness to immune maturation through a single metabolite. The same mechanism also enables niche expansion by enterotoxigenic strains, revealing context-dependent consequences. Notably, this strategy is distinct among gut Bacteroidales: other prominent members synthesize a different sphingolipid subclass supporting broader fitness, implying divergent evolutionary strategies. Our findings provide time-resolved insight into how bacterial metabolites shape host-microbiota symbiosis across development.
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