It has been shown that gut colonization of commensal bacteria decreases the risk of neonatal sepsis. This suggests that dysbiosis of the neonatal gut microbiota may represent a risk factor and contribute to increased incidence of infection in infants. Our ongoing experiments show that gut microbiota is altered by host adaptive immunity. We have found that immunocompromised mice harbor distinct gut microbial lineages from those in wild type mice. The difference exists in multiple anatomical sites including cecum, colonic contents, and colonic mucus. Strikingly, transferring mature B and T cells from wild type mice to immunodeficient mice alters the recipient mice's microbiota. These results indicate that host adaptive immune status plays a key role in shaping the gut microbiota. They beg the question, however, of the relative contributions of maternal and de novo immunity sources to the observed microbiota changes. In this study, we propose to focus on the effect of one maternal source, placenta, on neonatal microbiota compositions. We hypothesize that placenta-derived maternal factors, such as IgG and lymphocytes transferred through the placenta, can shape the gut microbiota in newborns with specific overrepresentation of certain bacterial taxa and depletion of others, and that lack of placenta factors leads to lower antibody levels in the circulation, and lower abundance of antibody-secreting B cells in the intestinal tract of infants. Heterozygous breeding and cross-fostering will be combined with next-generation sequencing to distinguish the placental effect from other potential modulators. We will address the hypothesis through two Specific Aims: 1) To determine differentially represented gut bacterial taxa with a loss of placental factors while keeping the milk factors intact, and 2) To determine differentially represented gut bacterial taxa with a gain of placental factors when milk-transmitted factors are absent.

Public Health Relevance

The contribution of placenta-derived immune factors to infant microbiota composition has not been revealed. Lack of such information has prevented identification of specific risk factors in the microbiota. The proposed research aims to improve neonatal health by identifying these risk factors, which in turn will lead to the design of probiotc therapies against neonatal infections and related complications.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Small Research Grants (R03)
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Gastrointestinal Mucosal Pathobiology Study Section (GMPB)
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Mills, Melody
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Virginia Polytechnic Institute and State University
Engineering (All Types)
Schools of Engineering
United States
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Mu, Qinghui; Tavella, Vincent J; Kirby, Jay L et al. (2017) Antibiotics ameliorate lupus-like symptoms in mice. Sci Rep 7:13675
Mu, Qinghui; Zhang, Husen; Liao, Xiaofeng et al. (2017) Control of lupus nephritis by changes of gut microbiota. Microbiome 5:73