Associations of serum trimethylamine N-oxide and its precursors with colorectal cancer risk in the Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial Cohort.

BACKGROUND: Dietary intake influences gut microbiome composition, which in turn may be associated with colorectal cancer (CRC). Associations of the gut microbiome with colorectal carcinogenesis may be mediated through bacterially regulated, metabolically active metabolites, including trimethylamine N-oxide (TMAO) and its precursors, choline, L-carnitine, and betaine. METHODS: Prospective associations of circulating TMAO and its precursors with CRC risk were investigated. TMAO, choline, betaine, and L-carnitine were measured in baseline serum samples from 761 incident CRC cases and 1:1 individually matched controls in the prospective Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial Cohort using targeted fully quantitative liquid chromatography tandem mass spectrometry panels. Prospective associations of the metabolites with CRC risk, using multivariable conditional logistic regression, were measured. Associations of a priori-selected dietary exposures with the four metabolites were also investigated. RESULTS: TMAO and its precursors were not associated with CRC risk overall, but TMAO and choline were positively associated with higher risk for distal CRC (continuous ORQ90 vs. Q10 [95% CI] = 1.90 [CI, 1.24-2.92; p = .003] and 1.26 [1.17-1.36; p < .0001], respectively). Conversely, choline was inversely associated with rectal cancer (ORQ90 vs. Q10 [95% CI] = 0.77 [0.76-0.79; p < .001]). Red meat, which was previously associated with CRC risk in the Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial Cohort , was positively associated with TMAO (Spearman rho = 0.10; p = .0003). CONCLUSIONS: Serum TMAO and choline may be associated with higher risk of distal CRC, and red meat may be positively associated with serum TMAO. These findings provide insight into a potential microbially mediated mechanism underlying CRC etiology.

Association Between Doula Use on a Digital Health Platform and Birth Outcomes.

OBJECTIVE: To examine the association between the use of virtual doula appointments on a comprehensive digital health platform and users' mode of birth and their birth experiences, among all platform users and Black platform users. METHODS: Data for this retrospective cohort study were extracted from individuals who enrolled in a comprehensive digital health platform, between January 1, 2020, and April 22, 2023. Multivariable logistic regression models were used to estimate the association between number of virtual doula appointments completed on the digital health platform and odds of cesarean birth and user-reported birth experience outcomes, which included help deciding a birth preference, receiving a high level of support during pregnancy, learning medically accurate information about pregnancy complications and warning signs, and managing mental health during pregnancy, stratified by parity. The interaction of doula utilization by race for each outcome was also tested. RESULTS: Overall 8,989 platform users were included. The completion of at least two appointments with a virtual doula on the digital health platform was associated with a reduction in odds of cesarean birth among all users (adjusted odds ratio [aOR] 0.80, 95% CI, 0.65-0.99) and among Black users (aOR 0.32, 95% CI, 0.14-0.72). Among platform users with a history of cesarean birth, completion of any number of doula visits was associated with a reduction in odds of repeat cesarean birth (one visit: aOR 0.35, 95% CI, 0.17-0.72; two or more visits: aOR 0.37, 95% CI, 0.17-0.83). Analyses among all users indicated dose-response associations between increased virtual doula use and greater odds of users reporting support in deciding a birth preference (one visit: aOR 2.35, 95% CI, 2.02-2.74; two or more visits: aOR 3.67, 95% CI, 3.03-4.44), receiving a high level of emotional support during pregnancy (one visit: aOR 1.99, 95% CI, 1.74-2.28; two or more visits: aOR 3.26, 95% CI, 2.70-3.94), learning medically accurate information about pregnancy complications and warning signs (one visit: aOR 1.26, 95% CI, 1.10-1.44; two or more visits: aOR 1.55, 95% CI, 1.29-1.88), and help managing mental health during pregnancy (one visit: aOR 1.28, 95% CI, 1.05-1.56; two or more visits: aOR 1.78, 95% CI, 1.40-2.26). CONCLUSION: This analysis demonstrates that virtual doula support on a digital health platform is associated with lower odds of cesarean birth and an improved birth experience. Positive findings among Black users and users with vaginal birth after cesarean suggest that doula support is critical for patient advocacy, and that digital health may play a meaningful role in increasing health equity in birth outcomes.

Stability of the Fecal and Oral Microbiome over 2 Years at -80°C for Multiple Collection Methods.

BACKGROUND: In prospective cohorts, biological samples are generally stored over long periods before an adequate number of cases have accrued. We investigated the impact of sample storage at -80°C for 2 years on the stability of the V4 region of the 16S rRNA gene across seven different collection methods (i.e., no additive, 95% ethanol, RNAlater stabilization solution, fecal occult blood test cards, and fecal immunochemical test tubes for feces; OMNIgene ORAL tubes and Scope mouthwash for saliva) among 51 healthy volunteers. METHODS: Intraclass correlation coefficients (ICC) were calculated for the relative abundance of the top three phyla, the 20 most abundant genera, three alpha-diversity metrics, and the first principal coordinates of three beta-diversity matrices. RESULTS: The subject variability was much higher than the variability introduced by the sample collection type, and storage time. For fecal samples, microbial stability over 2 years was high across collection methods (range, ICCs = 0.70-0.99), except for the samples collected with no additive (range, ICCs = 0.23-0.83). For oral samples, most microbiome diversity measures were stable over time with ICCs above 0.74; however, ICCs for the samples collected with Scope mouthwash were lower for two alpha-diversity measures, Faith's phylogenetic diversity (0.23) and the observed number of operational taxonomic units (0.23). CONCLUSIONS: Fecal and oral samples in most used collection methods are stable for microbiome analyses after 2 years at -80°C, except for fecal samples with no additive. IMPACT: This study provides evidence that samples stored for an extended period from prospective studies are useful for microbiome analyses.