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Mother-to-Infant Transfer of Bacteriome, Fungome, Virome, and Metabolome in Health and Crohn's Disease

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研究单位: [1]Chinese University of Hong Kong [2]The First Affiliated Hospital of Kunming Medical College [3]First People's Hospital of Foshan

研究目的:
Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are caused by the loss of mucosal tolerance towards the commensal microbiota resulting in inflammatory responses. Both CD and UC are difficult to manage clinically, and their incidences are increasing worldwide especially in newly industrialized countries. The etiology of these disorders is multifactorial, influenced by the complex interactions of genes, the immune system, intestinal microbiota, and the external environment. Studies have shown that there is a higher disease transmission rate from mothers with IBD than from fathers. It is well established that IBD is also associated with perturbations of gut microbiota composition. Early childhood is a golden age for microbiota manipulation to prevent disease. Studying microbiota at this golden age also allow us to dissect the development of a faulty microbiota and identify therapeutic targets to reverse it and cure diseases that are already developed. New evidence suggests that the gastrointestinal tract of new-borns becomes colonized with bacteria while in the womb, with the presence of different microbes. The source of these microbes is of continued interest because the initial intestinal colonization is believed to play a crucial role in the priming of the mucosal immune system and may predispose to the development of immune-mediated diseases, such as IBD, later in life. Overall, the microbiome structures in mother-babies across healthy and IBD populations are largely underexplored. A recent study discovered a novel mechanism of vertically transmitted protection of the new-born. The researchers found that bacteria in the mother's intestine during gestation can drive later innate maturation of the neonatal gut in the absence of colonization, through the transfer of specific bacterial metabolites to the foetus and via mother's milk. Study demonstrated that the effects of the gut microbiota on postnatal immune maturation are not simply due to colonization of the new-born after birth. Given the complexity of microbes present in the gestational gut, it will be exciting to learn whether there are other modules of priming induced by distinct microbes and their metabolites. Along these lines, it is tempting to speculate that this transgenerational effect represents a predictive adaptive response whereby mothers prepare the neonates for specific challenges that they are likely to encounter based on gestational environmental cues, not only by microbial colonisation but also by metabolite transfer. Meanwhile, it is unknown regarding whether there are abnormalities in the metabolome as well as its mother-to-infant transfer in IBD. Those results indicate that the metabolomic profiles are altered in IBD mother's breast milk, which may transfer to infants and influence their development and health.

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