Maternal Gestational <i>Bifidobacterium bifidum</i> TMC3115 Treatment Shapes Construction of Offspring Gut Microbiota and Development of Immune System and Induces Immune Tolerance to Food Allergens

Abstract

Background: Our previous studies has proved that Bifidobacterium bifidum TMC3115 (TMC3115) treatment during infancy could protect neonates from adulthood allergy. However, whether it could still protect offspring from allergic diseases when treatment during maternal pregnancy and the underlying mechanisms remain unclear. Methods: Pregnant BALB/c mice were gavaged with TMC3115 until delivery. Offspring were reared until weaning (postnatal day 21, PND21) and then sensitized with ovalbumin (OVA) until PND49. Vaginal, gut, and breast milk microbiota were sequenced. Immunoglobulin and cytokines, splenic and colonic gene expressions, and fecal short chain fatty acids (SCFAs) were measured. Findings: After maternal TMC3115 treatment, the microbiota of maternal breast milk from newborn offspring and gut microbiota of neonates and at weaning were changed the most, and levels of serum and breast milk immunoglobulin and of splenic cytokines as well as mRNA expression of colonic intestinal development indicators were all significantly altered in offspring in different stages. Synchronous changes in the specific microbiota were found in the maternal gut, vagina, and breast milk and in the offspring gut microbiota, such as Proteobacteria. After sensitization with OVA, there was no significant change in levels of serum IgE or OVA-specific IgE/IgG1 in the offspring in TMC3115 group; however, IgM, expression of colonic Ki67, Muc2, and tight junction proteins and production of fecal SCFAs were significantly increased as were the relative abundances of Lactobacillus and Lachnospiraceae NK4A136 group. Interpretation: Our results suggested that the day of birth and weaning were the important “window of opportunity” for neonatal gut microbiota construction and that maternal treatment with TMC3115 could play a profound modulatory effect on the development of the immune system in offspring at different stages. Maternal TMC3115 treatment may induce immune tolerance to allergens in OVA-stimulated offspring and enhance intestinal tissue development and barrier function and primary immune response to allergens through modulating gut microbiota and SCFA production. Funding Information: This work was supported by the National Natural Science Foundation of China (Grant number: 81372982). Declaration of Interests: The authors declare that they have no conflict of interest. Ethics Approval Statement: The animal experiment facility and animals used for the present study were officially approved by the Experimental Animal Management Committee of Sichuan Government. Experimental protocols were approved by the West China School of Public Health Medical Ethics Committee of Sichuan University (Approved number: SYXK2018-011).