Background: Short chain fatty acids (SCFAs) are microbially derived end products of dietary fiber fermentation. The SCFA butyrate reduces blood pressure (BP) in mouse models. The association of SCFAs, including butyrate, with BP in humans is unclear, due in part to predominantly cross‐sectional analyses and different biospecimens (blood versus fecal) for SCFA measurement. Longitudinal studies including both circulating and fecal SCFAs are lacking.Methods and Results: We leveraged existing data from the SPIRIT (Survivorship Promotion In Reducing IGF‐1 Trial), which randomized 121 adult cancer survivors with overweight/obesity to a behavioral weight‐loss intervention, metformin, or self‐directed weight‐loss. Of participants with baseline serum and fecal SCFAs measured (n=111), a subset had serum (n=93) and fecal (n=89) SCFA measurements 12 months later. We used Poisson regression with robust error variance to estimate baseline associations of SCFAs with hypertension, and we assessed the percent change in SCFAs from baseline with corresponding 12‐month changes in BP using multiple linear regression. Baseline fecal butyrate was inversely associated with prevalent hypertension (standardized PR [95%CI]: 0.71 [0.54, 0.92]). A 10% increase in fecal butyrate from baseline was associated with decreased systolic BP (β [95%CI]: −0.56 [−1.01, −0.10] mm Hg), and a 10% increase in serum butyrate was associated with decreased systolic (β [95%CI]: −1.39 [−2.15, −0.63] mm Hg) and diastolic (β [95%CI]: −0.55 [−1.03, −0.08] mm Hg) BPs. Butyrate associations with systolic BP were linear and not modified by sex, race, or intervention arm.Conclusions: Increased serum or fecal butyrate is associated with lowered BP. Butyrate may be a target for SCFA‐centered BP‐lowering interventions.Registration: URL:https://www.clinicaltrials.gov; Unique identifier: NCT02431676.

OBJECTIVE: Cross-sectional studies suggest that lipopolysaccharide-binding protein (LBP) may be associated with obesity and metabolic disorders. However, prospective studies examining LBP are lacking. This prospective study investigated the association between LBP and metabolic abnormalities in 580 African ancestry men (mean age, 59.1 ± 10.5 years). RESEARCH DESIGN AND METHODS: We measured fasting serum LBP at baseline. Changes in adiposity and glucose homeostasis as well as case subjects with new type 2 diabetes and impaired fasting glucose (IFG) were assessed at a follow-up visit ˜6 years later. Baseline LBP values were tested across quartiles for linear trend with metabolic measures. Multivariable logistic regression was used to determine the odds of new cases of IFG or diabetes per 1-SD greater baseline LBP. RESULTS: LBP was significantly associated with baseline BMI, waist circumference, whole-body and trunk fat, skeletal muscle density, fasting serum insulin, and HOMA-insulin resistance (IR) (all P < 0.01). Greater baseline LBP was significantly associated with longitudinal increases in the percentage of trunk fat (P = 0.025) and HOMA-IR (P = 0.034), but only borderline so with a decrease in skeletal muscle density (P = 0.057). In men with normal glucose, baseline LBP was associated with increased odds of having IFG at follow-up after adjustment for age, baseline trunk fat, and lifestyle factors (odds ratio per 1-SD LBP: 1.51; 95% CI 1.02–2.21). This association was attenuated after additional adjustment for change in trunk fat (P = 0.067). CONCLUSIONS: LBP may be a marker of prediabetes. Some of this association appears to be mediated through increased central and ectopic skeletal muscle adiposity.

Background/Objectives: Murine models show that plastics, via their chemical constituents (e.g., phthalates), influence microbiota, metabolism, and growth. However, research on plastics in humans is lacking. Here, we examine how the frequency of plastic bottle exposure is associated with fecal microbiota, short-chain fatty acids (SCFAs), and anthropometry in the first year of life. Subjects/Methods: In 442 infants from the prospective Nurture birth cohort, we examined the association of frequency of plastic bottle feeding at 3 months with anthropometric outcomes (skinfolds, length-for-age, and weight-for-length) at 12 months of age and growth trajectories between 3 and 12 months. Furthermore, in a subset of infants (n = 70) that contributed fecal samples at 3 months and 12 months of age, we examined plastic bottle frequency in relation to fecal microbiota composition and diversity (measured by 16S rRNA gene sequencing of V4 region), and fecal SCFA concentrations (quantified using gas chromatography mass spectrometry). Results: At 3 months, 67.6% of infants were plastic bottle fed at every feeding, 15.4% were exclusively breast milk fed, and 48.9% were exclusively formula fed. After adjustment for potential confounders, infants who were plastic bottle fed less than every feeding compared to those who were plastic bottle fed at every feeding at 3 months did not show differences in anthropometry over the first 12 months of life, save for lower length-for-age z-score at 12 months (adjusted β = −0.45, 95% CI: −0.76, −0.13). Infants who were plastic bottle fed less than every feeding versus every feeding had lower fecal microbiota alpha diversity at 3 months (mean difference for Shannon index: −0.59, 95% CI: −0.99, −0.20) and lower isovaleric acid concentration at 3 months (mean difference: −2.12 μmol/g, 95% CI: −3.64, −0.60), but these results were attenuated following adjustment for infant diet. Plastic bottle frequency was not strongly associated with microbiota diversity or SCFAs at 12 months after multivariable adjustment. Frequency of plastic bottle use was associated with differential abundance of some bacterial taxa, however, significance was not consistent between statistical approaches. Conclusions: Plastic bottle frequency at 3 months was not strongly associated with measures of adiposity or growth (save for length-for-age) over the first year of life, and while plastic bottle use was associated with some features of fecal microbiota and SCFAs in the first year, these findings were attenuated in multivariable models with infant diet. Future research is needed to assess health effects of exposure to other plastic-based products and objective measures of microplastics and plastic constituents like phthalates.