Obesity and colorectal neoplasm: Interaction between the gut microbiota and obesity-associated somatic genomic signals from colorectal adenoma and carcinoma

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K15920
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Yamagata University
• Principal Investigator: Sasaki Yu 山形大学, 医学部, 助教 (60466620)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 大腸発がん / 大腸癌 / 大腸腺腫 / 肥満 / インスリン抵抗性 / メタボリックシンドローム / LDL / E. faecalis

Outline of Final Research Achievements

Several epidemiological studies have indicated that individuals with obesity are at increased risk of colorectal cancer (CRC) and adenoma (CRA). The gut microbiota is affected by dietary patterns and obesity. Several studies have shown the mechanisms by which some bacteria might influence CRC development. Furthermore, accumulated DNA damage has been reported in individuals with obesity.
In this study, we demonstrated that several compositional alterations of the gut microbiota in patients with CRC and suggested that decreased E. faecalis is associated with the obesity-related CRC development. In addition, we found that the somatic alteration landscape differs between obese and non-obese in both CRA and CRC. The gut microbiota and these genomic alterations might be the targets to understand the mechanisms of obesity-associated colorectal carcinogenesis, and they might help to provide new preventive and therapeutic strategies.

Free Research Field

消化器内科

Academic Significance and Societal Importance of the Research Achievements

本邦で増え続けている肥満に関連した大腸がんにおける腸内細菌や遺伝子変化の特徴を明らかにしました。本病態の特徴を捉えることで、新しい予防や治療標的が創出できると考えられます。その結果、肥満関連大腸がんが征圧され、大腸がんになる患者さんの減少や死亡率の減少につなげることが可能となります。またこれらの知見は、世界に蔓延し、増加し続けている生活習慣病全般に関わる解析への応用も期待されます。