Abstract Diet has direct and indirect effects on health through inflammation and the gut microbiome. We investigated total dietary inflammatory potential via the literature-derived index (Dietary Inflammatory Index (DII®)) with gut microbiota diversity, composition and function. In cancer-free patient volunteers initially approached at colonoscopy and healthy volunteers recruited from the medical centre community, we assessed 16S ribosomal DNA in all subjects who provided dietary assessments and stool samples (n 101) and the gut metagenome in a subset of patients with residual fasting blood samples (n 34). Associations of energy-adjusted DII scores with microbial diversity and composition were examined using linear regression, permutational multivariate ANOVA and linear discriminant analysis. Spearman correlation was used to evaluate associations of species and pathways with DII and circulating inflammatory markers. Across DII levels, α- and β-diversity did not significantly differ; however, Ruminococcus torques, Eubacterium nodatum, Acidaminococcus intestini and Clostridium leptum were more abundant in the most pro-inflammatory diet group, while Akkermansia muciniphila was enriched in the most anti-inflammatory diet group. With adjustment for age and BMI, R. torques, E. nodatum and A. intestini remained significantly associated with a more pro-inflammatory diet. In the metagenomic and fasting blood subset, A. intestini was correlated with circulating plasminogen activator inhibitor-1, a pro-inflammatory marker (rho = 0·40), but no associations remained significant upon correction for multiple testing. An index reflecting overall inflammatory potential of the diet was associated with specific microbes, but not overall diversity of the gut microbiome in our study. Findings from this preliminary study warrant further research in larger samples and prospective cohorts.

BACKGROUND: High diet quality may support a metabolic and anti-inflammatory state less conducive to tumour progression. We prospectively investigated diet quality in relation to Gleason grade progression among localised prostate cancer patients on active surveillance, a clinical management strategy of disease monitoring and delayed intervention. METHODS: Men with newly diagnosed Gleason score 6 or 7 prostate cancer enroled on a biennial monitoring regimen. Patients completed a food frequency questionnaire (FFQ) at baseline (n = 411) and first 6-month follow-up (n = 263). Cox proportional hazards models were fitted to evaluate multivariable-adjusted associations of diet quality [defined via the Healthy Eating Index (HEI)-2015] with Gleason grade progression. RESULTS: After a median follow-up of 36 months, 76 men progressed. Following adjustment for clinicopathologic factors, we observed a suggestive inverse association between baseline diet quality and Gleason grade progression [hazard ratio (HR) and 95% confidence interval (CI) for the highest vs. the lowest HEI-2015 tertile: 0.59 (0.32-1.08); P trend = 0.06]. We observed no associations with diet quality at 6-month follow-up, nor change in diet quality from baseline. CONCLUSIONS: In localised prostate cancer patients on surveillance, higher diet quality or conformance with United States dietary guidelines at enrolment may lower risk of Gleason grade progression, though additional confirmatory research is needed.

BackgroundMouse and human studies support the promise of dry beans to improve metabolic health and to lower cancer risk. In overweight/obese patients with a history of colorectal polyps or cancer, the Beans to Enrich the Gut microbiome vs. Obesity’s Negative Effects (BE GONE) trial will test whether and how an increase in the consumption of pre-cooked, canned dry beans within the context of usual diet and lifestyle can enhance the gut landscape to improve metabolic health and reduce cancer risk.Methods/designThis randomized crossover trial is designed to characterize changes in (1) host markers spanning lipid metabolism, inflammation, and obesity-related cancer risk; (2) compositional and functional profiles of the fecal microbiome; and (3) host and microbial metabolites. With each subject serving as their own control, the trial will compare the participant’s usual diet with (intervention) and without (control) dry beans. Canned, pre-cooked dry beans are provided to participants and the usual diet continually assessed and monitored. Following a 4-week run-in and equilibration period, each participant provides a total of 5 fasting blood and 6 stool samples over a total period of 16 weeks. The intervention consists of a 2-week ramp-up of dry bean intake to 1 cup/d, which is then continued for an additional 6 weeks. Intra- and inter-individual outcomes are assessed across each crossover period with consideration of the joint or modifying effects of the usual diet and baseline microbiome.DiscussionThe BE GONE trial is evaluating a scalable dietary prevention strategy targeting the gut microbiome of high-risk patients to mitigate the metabolic and inflammatory effects of adiposity that influence colorectal cancer risk, recurrence, and survival. The overarching scientific goal is to further elucidate interactions between diet, the gut microbiome, and host metabolism. Improved understanding of the diet-microbiota interplay and effective means to target these relationships will be key to the future of clinical and public health approaches to cancer and other major diet- and obesity-related diseases.Trial registrationThis protocol is registered with the U.S. National Institutes of Health trial registry, ClinicalTrials.gov, under the identifier NCT02843425. First posted July 25, 2016; last verified January 25, 2019.

Accumulating evidence suggests that the gut microbiome’s role in early colorectal cancer etiology extends beyond the pro-carcinogenic activities of specific pathogens and is largely influenced by the wider microbial community of commensal bacteria. To identify early microbiome-related pathways and potential dietary intervention targets, we conducted an epidemiologic study among cancer-free colonoscopy patients at known and varied risk of colorectal neoplasia. Sporadic patients undergoing colonoscopy screening provided consent and fasting blood. Polyps, if found, were removed at colonoscopy and ~1 month later (prior studies show the effect of the colonoscopy prep dissipates within this time period), eligible patients provided a stool sample via mail kit (n=47). Patients completed comprehensive dietary assessments and clinicopathologic factors, including screening history, were abstracted from electronic medical records. We characterized the fecal microbiome via whole genome shotgun sequencing (Illumina HiSeq) and circulating blood adipocytokines via Luminex multiplex assays (Millipore). Majority of the patients were female and recently diagnosed with precancerous polyps, primarily tubular and sessile serrated adenomas. Polyp patients were more likely to be obese and to not consume alcohol, but otherwise similar by age, diet composition, and other risk factors to patients with normal colonoscopy findings. We observed no effects of time interval between colonoscopy and fecal sample collection, or of recent polyp diagnosis/removal, on microbial alpha or beta diversity. Correlation networks between species revealed that Faecalibacterium prausnitzii inversely correlated with E. coli, the most abundant species in our sample, and co-occurred with other short chain fatty acid-metabolizing bacteria, including Anaerostipes hadrus and Roseburia hominis, known butyrate-producers. Among recurrent patients (n=14), Bacteroides fragilis co-occurred with Bilophila wadsworthia (r=0.6; P=0.02). Higher intake of fiber and/or overall diet quality, as defined by the Healthy Eating Index, was associated with several bacteria largely linked to butyrate production (e.g., Bifidobacterium animalis, F. prausnitzii, Roseburia intestinalis, Coprococcus eutactus, Eubacterium eligens). These same dietary factors were inversely correlated with Blautia hydrogenotrophica, an acetogen, and other bacteria implicated in inflammation and colorectal cancer (e.g., B. fragilis). Biologically plausible associations between microbial (functional gene content) pathways important to cancer risk (e.g., one-carbon, lysine, carbohydrate and fatty acid metabolism) with dietary factors and circulating adipocytokines involved in immunity, inflammation, and glucose metabolism support the functionality of these diet-microbe relationships. Citation Format: Carrie R. Daniel, Kristi L. Hoffman, G S. Raju, Samir M. Hanash, Diane S. Hutchinson, Nadim J. Ajami, Richard G. Fowler, Gladys J. Browman, Akhil Sood, Paul Scheet, Xifeng Wu, Joseph F. Petrosino. Evidence of early colorectal cancer risk and prevention pathways in the fecal microbiome of colonoscopy patients: associations with diet and circulating adipocytokines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 238. doi:10.1158/1538-7445.AM2017-238

Background: Dry beans are a prebiotic food source rich in bioactive compounds with anti-inflammatory, anti-lipidemic and chemopreventive properties. The BE GONE trial tested the impact of an increase in dry bean consumption on gut microbiota and blood lipid profiles in high-risk colorectal (CR) patients otherwise consuming their usual diet. Methods: Following initiation of the pilot protocol (July 2016) among patients with a high-risk BMI and/or waist circumference and history of precancerous CR polyps, the crossover trial was expanded to patients with a history of CR cancer (May 2017). Patients were block randomized according to no vs. regular use of chronic disease medications commonly prescribed in the target population. Following a 4-week run-in/equilibration period, participants were randomized to continue the control diet (usual diet, no dry beans) or to begin the intervention diet (usual diet + dry beans). The intervention included a 2-week ramp-up to 1 cup/day navy beans (12 g dietary fiber; 14 g protein; 200 kcal) continued for an additional 6 weeks. Dietary habits, body weight, and other lifestyle parameters were monitored throughout the 20-week study. We characterized the 16Sv4 rDNA microbiome (Illumina MiSeq) and CLIA cholesterol panel in serial stool and fasting blood samples collected at baseline, week 4, and week 8 for each crossover period (n=249). Longitudinal analyses were conducted using generalized linear mixed models with random intercept and slope adjusted for chronic disease medication use examining the post-intervention effect from baseline to 4 weeks and baseline to 8 weeks. Results: Eligible patients were enrolled in the 4-week run-in/equilibration (n=69). Of these, 55 were randomized and 50 completed the 20-week trial in December 2019 with >80% compliance. Primary reasons for withdrawal were work/travel/family obligations. Half (54%) of the participants were male, 74% were CR cancer survivors, 76% were white (non-Hispanic) and 40% were on statins and/or metformin. Pre-study dietary profiles were characterized by low mean intake of legumes (<3 servings/month) and dietary fiber (17 g/day). The 8-week increase in bean intake significantly increased the inverse Simpson index [effect estimate and 95% CI: 1.59 (0.10, 3.08)], a diversity measure reflecting a greater variety of bacteria with a more even relative abundance. Longitudinal analyses restricted to taxa present in >80% of patients at baseline, revealed significantly decreased Anaerostipes and Streptococcus at week 4 and increased Faecalibacterium at week 8, along with temporal fluctuations in other known specialized (e.g., pectin) and versatile fiber-fermenting bacteria of the Lachnospiraceae and Ruminococcaceae families. A modest decrease in LDL cholesterol was observed at 8-weeks [-2.64 (-6.91, 1.62)] Conclusions: Early results of the BE GONE trial suggest that an 8-week increase in dry bean intake may be sufficient to balance or enrich the gut microbiome of high-risk CR patients. Continued sample processing and analysis, including stool metagenomics and blood metabolomics should continue to shed light on functional interactions relevant to the human host. Citation Format: Xiaotao Zhang, Kristi L. Hoffman, Fangyu Li, Ehsan Irajizad, Gladys Browman, Karen Basen-Engquist, Samir Hanash, Paul Scheet, Pablo C. Okhuysen, Scott Kopetz, Joseph Petrosino, Carrie R. Daniel. Beans to Enrich the Gut microbiome vs. Obesity's Negative Effects: First results from the BE GONE Trial in high-risk colorectal patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB223.