Maternal Gut Microbiome (MGM) Study of Diet, the Gut Microbiome and Preterm Birth
Condition: Preterm Birth
MeSH terms: Premature Birth
Study type: Observational

Summary: 
      The purpose of this study is to determine whether diet and the gut microbiome play a role in
      spontaneous preterm birth (SPTB), namely delivery of the fetus prior to 37 weeks gestation.
    

Detailed description: 
      While dietary guidelines about intake of specific nutrients in pregnant women are
      well-established, surprisingly little is known about dietary eating patterns or nutritional
      risk factors for SPTB.

      In data from two large nationally-representative European studies, SPTB was predicted by a
      western diet, a finding confirmed by a smaller cohort in Australia. In a small cohort in
      Poland, intake of short- and medium-chain fatty acids was lower in women who had SPTB, and
      the placental-fetal transport of fatty acids was significantly different in SPTB cases.
      Furthermore, more than a single serving daily of either artificially-sweetened or
      sugar-sweetened beverages was also linked to SPTB. Low blood biomarker levels of antioxidant
      nutrients (ascorbic, vitamin E)7 and nutrients with an established anti-inflammatory role in
      health (omega 3 fatty acids,8 vitamin D9-11) have been suggested as potential nutrient
      modulators of SPTB. While these are very interesting findings, they do not explain whether
      these food patterns prevail in an urban U.S. population or why SPTB occurs. Furthermore, none
      of these potentially modifiable diet associations has been examined in the context of the
      entire series of physiological systems operating during pregnancy, namely diet, the gut
      microbiome, maternal plasma metabolome, placenta, and cord blood.

      There is biological rationale to assume that dietary components could modify the gut
      microbiome and the maternal plasma metabolome during pregnancy. Artificial sweeteners induce
      glucose intolerance through an alternation in the gut microbiota. Chronic ingestion of
      sugar-sweetened beverages also results in similar plasma metabolic abnormalities (gut
      microbiome measures were not reported). In animal models of high fat diet feeding (similar to
      western diet), addition of N3FA ameliorated the gut dysbiosis and reduced endotoxin
      production. Furthermore, in healthy volunteers, the investigators have recently linked
      typical dietary intake patterns with the gut microbiome. Dietary patterns of high protein and
      animal fat intake were predominantly associated with Bacteroides enterotypes, while
      carbohydrate intake was associated with Prevotella. While the microbiome composition changes
      rapidly after change in diet, the enterotype identity is resilient over time. The
      investigators followed these findings with another study comparing the extreme diets of
      vegans (no animal products) to the more typical mixed western diet pattern of omnivores, and
      extended the analytical approaches to include assessment of the plasma metabolome. By
      observing the microbiome and metabolome, the investigators were clearly able to distinguish
      with 91% accuracy whether a subject was vegan or omnivore. Furthermore, the investigators
      could determine metabolomic characteristics that were contributed by gut bacterial
      metabolism, but only in subjects with high plant food intake. These findings in healthy
      volunteers raise the possibility that gut microbial populations could interact with maternal
      tissues or plasma to produce an inflammatory state that might result in preterm parturition.
      Indeed, the alteration of the gut microbiota observed in the third trimester of pregnancy and
      its effects on host metabolism are supportive of this notion.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Pregnant women will be recruited from three locations: Penn ObGyn Associates, Helen O.
        Dickens Clinic, and Maternal Fetal Medicine at 2000 Courtyard. Potential subjects will be
        identified from clinical schedules and will be pre-screened in EPIC for eligibility. They
        may be approached during a clinical visit, or the research team may call them prior to or
        after a scheduled visit to introduce the study. Women can be enrolled anytime between the
        confirmation of pregnancy and 24 weeks/0 days gestation. For convenience, research visits
        can be conducted at the time of a scheduled clinical visit, or at a separate time.
      
Biospecimen description: 
      1. Collect stool, maternal blood, cord blood, and placenta from women with preterm and term
      labor in order to investigate whether diet and gut microbiome play a role in preterm birth.
    
Keywords: Microbiome