Evidence map›Paper›PMID 41315359›Full record

ArticleNature communications2025

Genetically informed causal links between gut microbiota and bone mass: pleiotropy and metabolic mediation.

Peng-Lin Guan, Cheng-Da Yuan, Ming-Yu Han, Yi-Hu Fang, Chun-Fu Yu, Pian-Pian Zhao, Yu Qian, Jiang-Wei Xia, Peng Wei, Cai-Rui Liu and 7 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Peng-Lin Guan *College of Life Sciences, Zhejiang University, Hangzhou, China.ORCID 0009-0002-5603-2012
Cheng-Da Yuan *Department of Dermatology, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang, P.R. China.
Ming-Yu Han *Institute for immunity, Transplantation and Infection, Stanford Medicine, Stanford University, 1215 Welch Road, Modular B Stanford, Stanford, CA, USA.
Yi-Hu Fang *Jiangxi Medical College, Shangrao, Jiangxi, China.
Chun-Fu YuDepartment of Orthopedic Surgery, Shangrao Municipal Hospital, Shangrao, Jiangxi, China.
Pian-Pian ZhaoInstitute of Basic Medical Sciences, Westlake Institute for Advanced Study and Westlake University, Hangzhou, China.ORCID 0009-0009-1676-1748
Yu QianInstitute of Basic Medical Sciences, Westlake Institute for Advanced Study and Westlake University, Hangzhou, China.
Jiang-Wei XiaDepartment of Neurology, Xuanwu Hospital Capital Medical University, National Center for Neurological Disorders, Beijing, China.
Peng WeiSuzhou Laboratory of Precision Health and Data Science, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Cai-Rui LiuSuzhou Laboratory of Precision Health and Data Science, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Meng-Yuan YangSuzhou Laboratory of Precision Health and Data Science, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Wei XuSuzhou Laboratory of Precision Health and Data Science, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Ching-Lung CheungDepartment of Pharmacology and Pharmacy, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, SAR, China.ORCID 0000-0002-6233-9144
Shu-Yang XieBinzhou Medical University, Yantai, Shandong, China. xieshuyang@bzmc.edu.cn.ORCID 0000-0002-8090-2180
Fu-Sheng ZhouDepartment of Dermatology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China. biozhoufs@163.com.ORCID 0000-0003-4195-2801
Xiao-Li RongSuzhou Laboratory of Precision Health and Data Science, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China. rongxiaoli123@gmail.com.
Hou-Feng ZhengSuzhou Laboratory of Precision Health and Data Science, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China. houf.zheng@suda.edu.cn.ORCID 0000-0001-5681-8598

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The interplay among host genetic architecture, gut microbiota, metabolites and bone metabolism remains poorly understood. This study aims to comprehensively investigate the shared genetic factors, causal relationships, and the involvement of blood metabolites between gut microbiota and bone mass, based on datasets from European populations. Here, we estimate the polygenic SNP heritability for 1104 gut microbiota taxa, only 96 (8.7%) showed significant polygenic heritability. We identify 14 distinct gut microbiota taxa with pleiotropic effects on estimated heel bone mineral density (eBMD), 11 of them are found to have a causal association with eBMD. Following sensitivity and validation analyses, we find that the gut microbiota taxa family Bifidobacteriaceae; genus Bifidobacterium and species Bifidobacterium adolescentis exert causal effects leading to decreased eBMD. Mediation analyses indicate that the impact of these taxa on eBMD may be driven by their influence on circulating stearidonate (18:4n-3) levels via n-3 pathway, with mediating proportion from 77.53% to 87.24%. In conclusion, the genetically informed negative association between bifidobacterial taxa and bone mass may reflect the host-microbe interactions at LCT/MCM6 locus and represent an adaptive microbial response to lactose intolerance, thus, it could potentially be mitigated through supplementation with bifidobacterial probiotics and n-3 polyunsaturated fatty acids.

Indexed as

Bone and BonesBone DensityGastrointestinal MicrobiomeGenetic PleiotropyAdultBifidobacteriumFemaleHost Microbial InteractionsHumansLactose IntoleranceMaleMiddle AgedMultifactorial InheritancePolymorphism, Single Nucleotide

Identifiers

PMID41315359
PMCPMC12753762

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.