The influence of maternal unhealthy diet on maturation of gut microbiota in rat offspring from weaning to 14 weeks of age. Effect of unhealthy maternal diet on offspring gut microbiota

Background: The gut microbiota has significant impacts on host health. Diet has a well-established reciprocal relationship with gut microbiota composition. However, the influence of maternal consumption of healthy or unhealthy diets on the longitudinal maturation of gut microbiota in offspring are not well understood. To investigate this, we fed female rats a western-style, cafeteria diet (Caf) prior to and during mating, gestation and lactation. Male and female offspring were weaned onto chow or Caf diets, forming four offspring groups that were either maintained on their mother’s diet (ChowChow, CafCaf groups) or switched to the other diet at weaning (ChowCaf, CafChow). Fecal microbial composition of dams and offspring were assessed longitudinally at 3, 7 and 14 weeks of age. Results: At weaning, offspring gut microbiota was significantly different from that of older siblings and dams, characterised by significantly reduced α diversity, and β diversity profiles that clustered away from other groups. SourceTracker analyses showed increased Caf dam associated species in weaners’ gut microbiota, regardless of maternal diet. After weaning (3 weeks), offspring gut microbiota came to resemble the mother’s (adult-like) gut microbiota over time, with an increase in α diversity, reduced dissimilarity of β diversity, and fewer altered OTUs between groups. Continuous consumption of Caf diet throughout pregnancy to postnatal early life (CafCaf) altered β diversity of offspring gut microbiota compared with ChowChow group, however, the developmental trajectory of the offspring gut microbiota was consistent between ChowChow, CafCaf, ChowCaf and CafChow groups. Sex did not interact with the growth trajectory of offspring gut microbiota. Conclusions: Our study shows that the offspring gut microbiota community started maturing toward an adult-like gut microbiota when offspring were introduced to solid food. The developmental profiles of rat offspring gut microbiota are largely in agreement with previous human studies and implicate the cessation of lactation as an important trigger for early life gut microbiota development across species. The cessation of lactation and introduction of solid food is a critical window of offspring gut microbiota maturation.

背景：肠道菌群（gut microbiota）对宿主健康具有显著影响。饮食与肠道菌群组成之间已被证实存在双向互作关系。然而，母体摄入健康或不健康饮食对子代肠道菌群的纵向成熟过程的影响，目前仍未得到充分阐明。为探究这一问题，我们在交配前、交配期、妊娠期及哺乳期，给雌性大鼠喂食西式自助饮食（cafeteria diet，Caf）。将雌雄子代在断奶后分别喂食标准饲料或Caf饮食，形成四组子代：一组维持母代饮食（ChowChow组、CafCaf组），另一组在断奶后转换为另一种饮食（ChowCaf组、CafChow组）。分别在子代3、7、14周龄时，纵向评估母鼠及子代的粪便微生物组成。
结果：断奶时，子代肠道菌群与同窝年长子代及母鼠的菌群存在显著差异，表现为α多样性显著降低，且β多样性聚类特征与其他组别相分离。SourceTracker分析显示，无论母代饮食类型如何，断奶子代肠道菌群中与Caf母鼠相关的物种丰度均有所升高。断奶后（3周龄起），随着时间推移，子代肠道菌群逐渐趋近于母代菌群（成年样菌群），表现为α多样性升高、β多样性间的差异减小，组间差异的操作分类单元（operational taxonomic unit，OTU）数量减少。与ChowChow组相比，在妊娠至产后早期持续喂食Caf饮食的CafCaf组子代肠道菌群β多样性发生了改变，但ChowChow、CafCaf、ChowCaf及CafChow四组子代肠道菌群的发育轨迹并无显著差异。子代性别与肠道菌群生长轨迹无交互作用。
结论：本研究表明，当子代接触固体食物时，其肠道菌群群落即开始向成年样菌群成熟。大鼠子代肠道菌群的发育特征与此前的人类研究结果基本一致，提示泌乳终止是跨物种早期肠道菌群发育的重要触发因素。泌乳终止与固体食物的引入，是子代肠道菌群成熟的关键窗口期。