High-fat-diet-mediated dysbiosis promotes intestinal carcinogenesis independently of obesity
Manon D. Schulz,Çiğdem Atay,Jessica Heringer,Franziska K. Romrig,Sarah Schwitalla,Begüm Aydin,Paul K. Ziegler,Julia Varga,W Reindl,Claudia Pommerenke,Gabriela Salinas-Riester,Andreas Böck,Carl Alpert,Michael Blaut,Sara C. Polson,Lydia Brandl,Thomas Kirchner,Florian R. Greten,Shawn W. Polson,Melek C. Arkan +19 more
TLDR
It is demonstrated that an HFD promotes tumour progression in the small intestine of genetically susceptible, K-rasG12Dint, mice independently of obesity, and this data underscore the importance of the reciprocal interaction between host and environmental factors in selecting a microbiota that favours carcinogenesis.Abstract:
Several features common to a Western lifestyle, including obesity and low levels of physical activity, are known risk factors for gastrointestinal cancers. There is substantial evidence suggesting that diet markedly affects the composition of the intestinal microbiota. Moreover, there is now unequivocal evidence linking dysbiosis to cancer development. However, the mechanisms by which high-fat diet (HFD)-mediated changes in the microbial community affect the severity of tumorigenesis in the gut remain to be determined. Here we demonstrate that an HFD promotes tumour progression in the small intestine of genetically susceptible, K-ras(G12Dint), mice independently of obesity. HFD consumption, in conjunction with K-ras mutation, mediated a shift in the composition of the gut microbiota, and this shift was associated with a decrease in Paneth-cell-mediated antimicrobial host defence that compromised dendritic cell recruitment and MHC class II molecule presentation in the gut-associated lymphoid tissues. When butyrate was administered to HFD-fed K-ras(G12Dint) mice, dendritic cell recruitment in the gut-associated lymphoid tissues was normalized, and tumour progression was attenuated. Importantly, deficiency in MYD88, a signalling adaptor for pattern recognition receptors and Toll-like receptors, blocked tumour progression. The transfer of faecal samples from HFD-fed mice with intestinal tumours to healthy adult K-ras(G12Dint) mice was sufficient to transmit disease in the absence of an HFD. Furthermore, treatment with antibiotics completely blocked HFD-induced tumour progression, suggesting that distinct shifts in the microbiota have a pivotal role in aggravating disease. Collectively, these data underscore the importance of the reciprocal interaction between host and environmental factors in selecting a microbiota that favours carcinogenesis, and they suggest that tumorigenesis is transmissible among genetically predisposed individuals.read more
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Inflammation and Cancer: Triggers, Mechanisms, and Consequences.
TL;DR: How tumor-promoting inflammation closely resembles inflammatory processes typically found during development, immunity, maintenance of tissue homeostasis, or tissue repair is discussed and the distinctions between tissue-protective and pro-tumorigenic inflammation are illuminated.
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Cancer and the microbiota
TL;DR: This Review considers how microbes and the microbiota may amplify or mitigate carcinogenesis, responsiveness to cancer therapeutics, and cancer-associated complications.
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Maturation of the infant microbiome community structure and function across multiple body sites and in relation to mode of delivery.
TL;DR: It is concluded that within the first 6 weeks of life, the infant microbiota undergoes substantial reorganization, which is primarily driven by body site and not by mode of delivery.
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Diet, microorganisms and their metabolites, and colon cancer
TL;DR: The mechanisms behind microbial metabolite effects, which could be modified by diet to achieve the objective of preventing colorectal cancer in Western societies are discussed.
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Nutrients, Foods, and Colorectal Cancer Prevention
TL;DR: Diet modification has the promise of reducing colorectal cancer incidence and emerging evidence also implicates the gut microbiota as an important effector in the relationship between diet and cancer.
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