Department of Neurobiology, The University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy.
Department of Neurobiology, The University of Texas Medical Branch, Galveston, TX 77555, USA.
Cell Rep. 2022 Oct 11;41(2):111461. doi: 10.1016/j.celrep.2022.111461.
Dysbiosis of the maternal gut microbiome during pregnancy is associated with adverse neurodevelopmental outcomes. We previously showed that maternal high-fat diet (MHFD) in mice induces gut dysbiosis, social dysfunction, and underlying synaptic plasticity deficits in male offspring (F). Here, we reason that, if HFD-mediated changes in maternal gut microbiota drive offspring social deficits, then MHFD-induced dysbiosis in F female MHFD offspring would likewise impair F social behavior. Metataxonomic sequencing reveals reduced microbial richness among female F MHFD offspring. Despite recovery of microbial richness among MHFD-descendant F mice, they display social dysfunction. Post-weaning Limosilactobacillus reuteri treatment increases the abundance of short-chain fatty acid-producing taxa and rescues MHFD-descendant F social deficits. L. reuteri exerts a sexually dimorphic impact on gut microbiota configuration, increasing discriminant taxa between female cohorts. Collectively, these results show multigenerational impacts of HFD-induced dysbiosis in the maternal lineage and highlight the potential of maternal microbiome-targeted interventions for neurodevelopmental disorders.
怀孕期间母体肠道微生物组的失调与不良神经发育结果有关。我们之前的研究表明,在小鼠中给予高脂肪饮食(HFD)会导致肠道菌群失调、社交功能障碍以及雄性后代(F)潜在的突触可塑性缺陷。在这里,我们推断,如果 HFD 引起的母体肠道微生物组变化导致后代的社交缺陷,那么 MHFD 诱导的 F 雌性 MHFD 后代的失调也会损害 F 的社交行为。分类学测序显示雌性 F MHFD 后代的微生物丰富度降低。尽管 MHFD 后代的微生物丰富度恢复,但它们仍表现出社交功能障碍。断奶后补充罗伊氏乳杆菌可增加短链脂肪酸产生菌的丰度,并挽救 MHFD 后代的社交缺陷。L. reuteri 对肠道微生物群结构具有性别二态性影响,增加了雌性队列之间的区分性分类群。总之,这些结果表明 HFD 诱导的母体谱系失调具有多代影响,并强调了针对母体微生物组的干预措施对神经发育障碍的潜在影响。