Randomized control trial of moderate dose vitamin D alters microbiota stability and metabolite networks in healthy adults.

Evidence indicates that both vitamin D and the gut microbiome are involved in the process of colon carcinogenesis. However, it is unclear what effects supplemental vitamin D3 has on the gut microbiome and its metabolites in healthy adults. We conducted a double-blind, randomized, placebo-controlled trial to identify the acute and long-term microbiota structural and metabolite changes that occur in response to a moderate dose (4,000 IU) of vitamin D3 for 12 weeks in healthy adults. Our results demonstrated a significant increase in serum 25-hydroxy-vitamin D (25(OH)D) in the treatment group compared to placebo (P < 0.0001). Vitamin D3 significantly increased compositional similarity (P < 0.0001) in the treatment group, and enriched members of the Bifidobacteriaceae family. We also identified a significant inverse relationship between the percent change in serum 25(OH)D and microbial stability in the treatment group (R = -0.52, P < 0.019). Furthermore, vitamin D3 supplementation resulted in notable metabolic shifts, in addition to resulting in a drastic rewiring of key gut microbial-metabolic associations. In conclusion, we show that a moderate dose of vitamin D3 among healthy adults has unique acute and persistent effects on the fecal microbiota, and suggest novel mechanisms by which vitamin D may affect the host-microbiota relationship. IMPORTANCE: Preventative measures to reduce the rise in early-onset colorectal cancer are of critical need. Both vitamin D, dietary and serum levels, and the gut microbiome are implicated in the etiology of colorectal cancer. By understanding the intimate relationship between vitamin D, the gut microbiome, and its metabolites, we may be able to identify key mechanisms that can be targeted for intervention, including inflammation and metabolic dysfunction. Furthermore, the similarity of vitamin D to cholesterol, which is metabolized by the gut microbiome, gives precedence to its ability to produce metabolites that can be further studied and leveraged for controlling colorectal cancer incidence and mortality.

Diet-microbiome interactions in cancer treatment: Opportunities and challenges for precision nutrition in cancer.

Dietary patterns contribute to cancer risk. Separately, microbial factors influence the development of several cancers. However, the interaction of diet and the microbiome and their joint contribution to cancer treatment response needs more research. The microbiome significantly impacts drug metabolism, immune activation, and response to immunotherapy. One of the critical factors affecting the microbiome structure and function is diet. Data demonstrate that the diet and microbiome composition affects the immune response. Moreover, malnutrition is a significant confounder to cancer therapy response. There is little understanding of the interaction of malnutrition with the microbiome in the context of cancer. This review aims to address the current knowledge of dietary intake patterns and malnutrition among cancer patients and the impact on treatment outcomes. Second, this review will provide evidence linking the microbiome to cancer treatment response and provide evidence of the potentially strong effect that diet could have on this interaction. This review will formulate critical questions that will need further research to understand the diet-microbiome relationship in cancer treatment response and directions for future research to guide us to precision nutrition therapy to improve cancer outcomes.

Targeting Dietary and Microbial Tryptophan-Indole Metabolism as Therapeutic Approaches to Colon Cancer.

Tryptophan metabolism, via the kynurenine (Kyn) pathway, and microbial transformation of tryptophan to indolic compounds are fundamental for host health; both of which are altered in colon carcinogenesis. Alterations in tryptophan metabolism begin early in colon carcinogenesis as an adaptive mechanism for the tumor to escape immune surveillance and metastasize. The microbial community is a key part of the tumor microenvironment and influences cancer initiation, promotion and treatment response. A growing awareness of the impact of the microbiome on tryptophan (Trp) metabolism in the context of carcinogenesis has prompted this review. We first compare the different metabolic pathways of Trp under normal cellular physiology to colon carcinogenesis, in both the host cells and the microbiome. Second, we review how the microbiome, specifically indoles, influence host tryptophan pathways under normal and oncogenic metabolism. We conclude by proposing several dietary, microbial and drug therapeutic modalities that can be utilized in combination to abrogate tumorigenesis.