Premium
Nicotine exposure during pregnancy alters the maternal gut microbiome and both cecal and plasma short chain fatty acids in Sprague Dawley rats.
Author(s) -
Hayward Linda,
Watkins Jacqueline,
Bautista Byrell,
Lin Cindy,
Malphurs Wendi,
Zubcevic Jasenka
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.03967
Subject(s) - pregnancy , firmicutes , physiology , nicotine , verrucomicrobia , gut flora , bacterial vaginosis , endocrinology , biology , dysbiosis , microbiome , medicine , fatty acid , immunology , microbiology and biotechnology , biochemistry , bioinformatics , genetics , 16s ribosomal rna , gene
Children of mothers that smoke during pregnancy are more likely to be obese and develop high blood pressure, suggesting a developmental origin of these diseases. Evidence now suggests that an imbalance of the bacterial microbes in the gastrointestinal tract may also play an important role these diseases. Thus, the present study was undertaken to test the hypothesis that nicotine‐exposure during pregnancy alters the maternal gut‐microbiome, inducing gut dysbiosis that may be passed on to the child during birth and/or shifts in bacterial metabolites, such as short chain fatty acids (SCFAs), that the fetus is exposed to in utero . To test our hypothesis, age‐matched virgin and pregnant female rats were exposed to nicotine (6 mg/kg/day) or vehicle (saline) via osmotic mini pump, including days 6–18 of pregnancy. Cecal contents, tissue from the proximal colon, and plasma were collected on day 14 of treatment. A two‐way ANOVA (pregnant state x treatment) identified that pregnancy decreased the abundance of bacteria in the phyla Firmicutes , while increasing the abundance of Actinobacteria and Verrucomicrobia compared to virgin rats (P<0.02). Nicotine exposure, independent of pregnancy, further increased the abundance of Actinobacteria (P<0.03) and tended to increase the proportion of Firmicutes and decrease the abundance of Verrucomicrobia . Evaluation of cecal SCFAs identified that pregnancy upregulated the abundance of acetate and propionic acid (P<0.02) and tended to upregulate butyric and hexanoic acid. Conversely, nicotine exposure, independent of pregnancy, decreased cecal acetate (P<0.02), propionic acid (P<0.007), and hexanoic acid (P<0.009) concentrations. Similarly, plasma levels of acetate, propionic, butyric, and valeric acid were upregulated by pregnancy, and nicotine exposure, independent of pregnant state, reversed this trend (P<0.05). Finally, gene expression in the proximal colon identified that pregnancy triggered an upregulation of multiple genes, including the protective enzyme 11‐beta HSD2, the sodium channel ENAC, Ffar2, the SCFA acetate and propionate transporter, the solute carrier SMCT1, and Tph2, the rate limiting enzyme for serotonin production (P<0.05). Independent of pregnancy status, nicotine downregulated the expression of all five genes. These results confirm our hypothesis that nicotine exposure during pregnancy can significantly alter the maternal gut microbiome and affect fetal exposure to specific circulating factors linked to gut microbial metabolism. These findings provide a new link between changes in the maternal gut microbiome and the fetal origins of adult diseases. Support or Funding Information FL DOH James and Esther King Biomedical Research Program 8JK06