麻省理工学院和哈佛大学的布罗德研究所Po-Ru Loh小组取得一项新突破。他们开发出人类和细菌的遗传变异塑造口腔微生物群和健康。该项研究成果发表在2026年1月28日出版的《自然》上。

该课题组人员通过重新分析先前测序的唾液来源DNA的全基因组测序读数，对12519人的口腔微生物组进行了表征。11个位点（10个新位点）的人类遗传变异与口腔微生物组组成的变异相关。其中一些与碳水化合物的可用性有关；最强关联（P = 3.0 × 10^-188)涉及共同的FUT2W154X功能缺失变异，与58种细菌的丰度相关。人类宿主遗传似乎也有力地塑造了口腔细菌物种的遗传变异：这11种宿主遗传变异也与细菌基因组68个区域的基因剂量变异有关。编码唾液淀粉酶的AMY1常见的多等位基因拷贝数变异与口腔微生物组组成相关（P = 1.5 × 10^-53）和英国生物银行（UK Biobank）假牙主题(P = 5.9 × 10^-35岁,n = 418039)，但与体重指数无关（P = 0.85），这表明唾液淀粉酶丰度通过影响口腔微生物群影响健康。另外两个微生物组相关基因座FUT2和PITX1也与假牙风险显著相关，它们共同指出了许多导致蛀牙的宿主-微生物相互作用。

据了解，人类遗传变异影响其生物学的各个方面，包括口腔，营养物质和微生物通过口腔进入人体。然而，哪些人类基因变异塑造了一个人的口腔微生物群，并可能促进其生态失调，这在很大程度上是未知的。

附：英文原文

Title: Human and bacterial genetic variation shape oral microbiomes and health

Author: Kamitaki, Nolan, Handsaker, Robert E., Hujoel, Margaux L. A., Mukamel, Ronen E., Usher, Christina L., McCarroll, Steven A., Loh, Po-Ru

Issue&Volume: 2026-01-28

Abstract: Human genetic variation influences all aspects of our biology, including the oral cavity1,2,3, through which nutrients and microbes enter the body. Yet it is largely unknown which human genetic variants shape a person’s oral microbiome and potentially promote its dysbiosis3,4,5. We characterized the oral microbiomes of 12,519 people by re-analysing whole-genome sequencing reads from previously sequenced saliva-derived DNA. Human genetic variation at 11 loci (10 new) associated with variation in oral microbiome composition. Several of these related to carbohydrate availability; the strongest association (P=3.0×10188) involved the common FUT2W154X loss-of-function variant, which associated with the abundances of 58 bacterial species. Human host genetics also seemed to powerfully shape genetic variation in oral bacterial species: these 11 host genetic variants also associated with variation of gene dosages in 68 regions of bacterial genomes. Common, multi-allelic copy number variation of AMY1, which encodes salivary amylase, associated with oral microbiome composition (P=1.5×1053) and with dentures use in UK Biobank (P=5.9×1035, n=418,039) but not with body mass index (P=0.85), suggesting that salivary amylase abundance impacts health by influencing the oral microbiome. Two other microbiome composition-associated loci, FUT2 and PITX1, also significantly associated with dentures risk, collectively nominating numerous host–microbial interactions that contribute to tooth decay.

DOI: 10.1038/s41586-025-10037-7

Source: https://www.nature.com/articles/s41586-025-10037-7