Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston.
Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston.
JAMA Netw Open. 2021 Nov 1;4(11):e2134308. doi: 10.1001/jamanetworkopen.2021.34308.
Sulfur-metabolizing bacteria that reduce dietary sulfur to hydrogen sulfide have been associated with colorectal cancer (CRC). However, there are limited studies investigating the association between diet and sulfur-metabolizing bacteria in the development of CRC.
To develop a dietary score that correlates with gut sulfur-metabolizing bacteria and to examine its association with CRC risk.
DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study included data from the Health Professionals Follow-up Study (1986-2014), Nurses' Health Study (1984-2016), and Nurses' Health Study II (1991-2017). Participants were US male health professionals and female registered nurses who were free of inflammatory bowel disease and cancer at baseline, with a subsample of participants who provided stool samples from 2012 to 2014. Statistical analysis was conducted from September 1, 2020, to June 1, 2021.
A dietary pattern, assessed by a food-frequency questionnaire, that most correlated with 43 sulfur-metabolizing bacteria identified through taxonomic and functional profiling of gut metagenome data.
Incident CRC.
Among 214 797 participants comprising 46 550 men (mean [SD] age at baseline, 54.3 [9.7] years) and 168 247 women (mean [SD] age at baseline, 43.0 [9.2] years), 3217 incident cases of CRC (1.5%) were documented during 5 278 048 person-years of follow-up. The sulfur microbial diet, developed in a subsample of 307 men (mean [SD] age, 70.5 [4.3] years) and 212 women (mean [SD] age, 61.0 [3.8] years), was characterized by high intakes of low-calorie beverages, french fries, red meats, and processed meats and low intakes of fruits, yellow vegetables, whole grains, legumes, leafy vegetables, and cruciferous vegetables. After adjustment for other risk factors, greater adherence to the sulfur microbial diet was associated with an increased risk of CRC, with a hazard ratio (HR) of 1.27 (95% CI, 1.12-1.44) comparing the highest vs the lowest quintile of the diet score (linear trend of diet score quintiles; P < .001 for trend). When assessed by anatomical subsites, greater adherence to the sulfur microbial diet was positively associated with distal CRC (HR, 1.25; 95% CI, 1.05-1.50; P = .02 for trend) but not proximal colon cancer (HR, 1.13; 95% CI, 0.93-1.39; P = .19 for trend).
Adherence to the sulfur microbial diet was associated with an increased risk of CRC, suggesting a potential mediating role of sulfur-metabolizing bacteria in the associaton between diet and CRC. Further research is needed to confirm these findings and to determine the underlying mechanisms.
将饮食中的硫还原为硫化氢的硫代谢细菌与结直肠癌（CRC）有关。然而，关于饮食与 CRC 发展过程中硫代谢细菌之间的关联，研究有限。
开发一种与肠道硫代谢细菌相关的饮食评分，并研究其与 CRC 风险的相关性。
设计、地点和参与者：本前瞻性队列研究的数据来自卫生专业人员随访研究（1986-2014 年）、护士健康研究（1984-2016 年）和护士健康研究 II（1991-2017 年）。参与者为美国男性健康专业人员和注册女护士，在基线时无炎症性肠病和癌症，其中一部分参与者提供了 2012 年至 2014 年的粪便样本。统计分析于 2020 年 9 月 1 日至 2021 年 6 月 1 日进行。
通过食物频率问卷评估的饮食模式，与通过肠道宏基因组数据的分类和功能分析确定的 43 种硫代谢细菌最相关。
CRC 新发病例。
在包括 46550 名男性（基线时平均[SD]年龄为 54.3[9.7]岁）和 168247 名女性（基线时平均[SD]年龄为 43.0[9.2]岁）在内的 214797 名参与者中，在 5278048 人年的随访中记录到 3217 例 CRC（1.5%）新发病例。在由 307 名男性（平均[SD]年龄为 70.5[4.3]岁）和 212 名女性（平均[SD]年龄为 61.0[3.8]岁）组成的亚组中，硫微生物饮食的特点是高摄入低热量饮料、炸薯条、红色肉类和加工肉类，以及低摄入水果、黄色蔬菜、全谷物、豆类、绿叶蔬菜和十字花科蔬菜。在调整了其他风险因素后，与硫微生物饮食的依从性更高与 CRC 风险增加相关，最高五分位组与最低五分位组的 HR 为 1.27（95%CI，1.12-1.44）（饮食评分五分位线性趋势；P<0.001）。当按解剖部位评估时，与硫微生物饮食的更高依从性与远端 CRC（HR，1.25；95%CI，1.05-1.50；P=0.02 用于趋势）呈正相关，但与近端结肠癌（HR，1.13；95%CI，0.93-1.39；P=0.19 用于趋势）无关。
与硫微生物饮食的依从性与 CRC 风险增加相关，表明硫代谢细菌在饮食与 CRC 之间的关联中可能起中介作用。需要进一步研究来证实这些发现并确定潜在的机制。
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