Colorectal cancer (CRC) is associated with multiple risk factors including, obesity, low
fiber diets, and diets high in animal protein and saturated fat (SFat). African Americans
(AAs) have a higher prevalence of these risk factors and they have the highest incidence
of CRC and related mortality. These multiple risk factors are also linked to higher
circulating and fecal bile acids (BA) and a shift in BA amino acid conjugation from
glycine to taurine. These BA-related changes can alter the composition, structure, and
metabolic activity of the gut microbiota, fostering conditions for gut bacteria to expand
and metabolize taurine-conjugated BAs to genotoxic hydrogen sulfide (H2S) and the tumor
promoter, deoxycholic acid (DCA); a colonic milieu conducive to the formation of CRC. The
investigators have shown that the abundance of H2S-producing bacteria is significantly
higher in the colon of AAs compared to non-Hispanic whites (NHWs) and is a defining
feature among AA CRC cases implicating these bacteria as contributors to CRC development
in a race-dependent manner. Moreover, the microbial difference is associated with higher
intake of SFat and animal protein in AAs, providing a pivotal intervention target. The
investigators hypothesize that targeting the BA-gut microbiome axis to suppress
abundance, growth and metabolic activity of H2S and DCA producing bacteria through diet
and weight loss (WL) may reduce CRC risk, especially among AAs. A Mediterranean Diet
(MedDiet), a largely plant-based dietary pattern, is relevant to CRC prevention and
microbial production of anti-cancer metabolites in observational studies. A MedDiet can
shift BA metabolism as shown in primates and when combined with calorie restriction,
shows superior adherence and weight control in humans, given its palatability. To date,
no studies have tested in an RCT the effects of a MedDiet alone (MedA), WL through
lifestyle intervention (WL-A) or a calorie-restricted MedDiet for WL (WL-Med) on the
BA-gut microbiome axis and its relevance to CRC prevention among AAs. Our
multidisciplinary team combining expertise in psychology, nutrition, microbiology,
molecular cell biology, computational biology, medicine and biostatistics, propose to
conduct a four-arm RCT in which 232 obese AAs, 45-75 years old complete one of the
following 6-month interventions: Med-A, weight stable; WL-A, calorie restriction with no
diet pattern change; WLMed; or Control. The investigators will use samples and data
collected at baseline, mid-study (month-3) and post-intervention to compare the effects
of the interventions on 1) Concentration and composition of circulating and fecal BAs; 2)
Gut microbiota and metabolic function; and 3) Gene expression profiles of exfoliated
intestinal epithelial cells. The investigators approach is strong given the
multidisciplinary team, use of evidence-based lifestyle interventions, and sophisticated
-omics analyses to examine crosstalk between diet/WL, gut microbiome, and host intestinal
physiology. If successful, this study could have profound public health impact on CRC
risk among AAs and other high-risk populations, that would translate into timely
dissemination opportunities.
