Maternal Gut Microbiome (MGM) Study of Diet, the Gut Microbiome and Preterm Birth

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.

Inclusion Criteria:

- Pregnant women receiving care in University of Pennsylvania Health System

- Between 16-24 weeks gestation

Exclusion Criteria:

- Multiple gestation

- Fetal chromosomal abnormality or major fetal anomaly

- Intrauterine fetal demise

- Maternal HIV

- Chronic kidney disease

- Transplant

- Prior weight loss surgery

- Vegan diet

- Chronic use of immunosuppresive medications or steriods