1.
Diet-microbiome interactions in cancer treatment: Opportunities and challenges for precision nutrition in cancer.
Greathouse, KL, Wyatt, M, Johnson, AJ, Toy, EP, Khan, JM, Dunn, K, Clegg, DJ, Reddy, S
Neoplasia (New York, N.Y.). 2022;:100800
Abstract
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.
2.
Targeting Dietary and Microbial Tryptophan-Indole Metabolism as Therapeutic Approaches to Colon Cancer.
Wyatt, M, Greathouse, KL
Nutrients. 2021;(4)
Abstract
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.
3.
Author Correction: Interaction between the microbiome and TP53 in human lung cancer.
Greathouse, KL, White, JR, Vargas, AJ, Bliskovsky, VV, Beck, JA, von Muhlinen, N, Polley, EC, Bowman, ED, Khan, MA, Robles, AI, et al
Genome biology. 2020;(1):41
Abstract
Following publication of the original paper [1], the authors submitted a new Additional file 5 to replace the one containing formatting issues. The updated Additional file 5 is published in this correction.
4.
DNA extraction for human microbiome studies: the issue of standardization.
Greathouse, KL, Sinha, R, Vogtmann, E
Genome biology. 2019;(1):212
Abstract
Among the laboratory and bioinformatic processing steps for human microbiome studies, a lack of consistency in DNA extraction methodologies is hindering the ability to compare results between studies and sometimes leading to errant conclusions. The purpose of this article is to highlight the issues related to DNA extraction methods and to suggest minimum standard requirements that should be followed to ensure consistency and reproducibility.
5.
Interaction between the microbiome and TP53 in human lung cancer.
Greathouse, KL, White, JR, Vargas, AJ, Bliskovsky, VV, Beck, JA, von Muhlinen, N, Polley, EC, Bowman, ED, Khan, MA, Robles, AI, et al
Genome biology. 2018;(1):123
Abstract
BACKGROUND Lung cancer is the leading cancer diagnosis worldwide and the number one cause of cancer deaths. Exposure to cigarette smoke, the primary risk factor in lung cancer, reduces epithelial barrier integrity and increases susceptibility to infections. Herein, we hypothesize that somatic mutations together with cigarette smoke generate a dysbiotic microbiota that is associated with lung carcinogenesis. Using lung tissue from 33 controls and 143 cancer cases, we conduct 16S ribosomal RNA (rRNA) bacterial gene sequencing, with RNA-sequencing data from lung cancer cases in The Cancer Genome Atlas serving as the validation cohort. RESULTS Overall, we demonstrate a lower alpha diversity in normal lung as compared to non-tumor adjacent or tumor tissue. In squamous cell carcinoma specifically, a separate group of taxa are identified, in which Acidovorax is enriched in smokers. Acidovorax temporans is identified within tumor sections by fluorescent in situ hybridization and confirmed by two separate 16S rRNA strategies. Further, these taxa, including Acidovorax, exhibit higher abundance among the subset of squamous cell carcinoma cases with TP53 mutations, an association not seen in adenocarcinomas. CONCLUSIONS The results of this comprehensive study show both microbiome-gene and microbiome-exposure interactions in squamous cell carcinoma lung cancer tissue. Specifically, tumors harboring TP53 mutations, which can impair epithelial function, have a unique bacterial consortium that is higher in relative abundance in smoking-associated tumors of this type. Given the significant need for clinical diagnostic tools in lung cancer, this study may provide novel biomarkers for early detection.