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The adverse factors impacting the intestinal microbiota of newborns remain to be elucidated. We put forward a hypothesis that hyperoxia in combination with rituximab exhibits a synergistic effect that interferes with neonatal intestinal microbiota. Six C57BL/6J mice, aged 12 weeks and pregnant 18 days, were purchased. Their pups were breastfed and raised under a 75% oxygen or conventional environment. Low‐ (20 mg/kg) and high‐dose (40 mg/kg) rituximab were intraperitoneally administered. Fecal genomic DNA was extracted and sequenced by a 16S rRNA platform. Severe intestinal dysbiosis in newborns were observed, whereas mild dysbiosis was caused by inducing hyperoxia alone, confirming the synergistic interference of the combination of hyperoxia and B‐cell antagonist (rituximab) in neonatal intestinal microbiota disruption. Slight dysbiosis was observed in the intestinal microbiota of dams, indicating their much robust ability to confront hyperoxic conditions. The abundance of  Akkermansia muciniphila  was significantly and extensively altered in both pups and dams after being subjecting them to hyperoxic conditions with or without rituximab administration. In conclusion, this work demonstrated that the synergistic effect of hyperoxia and rituximab led to severe intestinal dysbiosis in newborns. More studies are recommended to explore the precise regulatory mode between hyperoxia and rituximab in intestinal microbiota.

Hyperoxia combined with the B‐cell antagonist rituximab led to intestinal dysbiosis in neonatal mice