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. 2025 Aug 8;23(1):468.
doi: 10.1186/s12916-025-04307-4.

Plasma biomarkers of dairy intake and gut microbiome, and their association with incident carotid plaque: a prospective cohort study

Congmei Xiao #  1 , Qian Chen #  2 , Menglei Shuai #  1   3 , Chang Gao  1   3 , Wanglong Gou  1   4 , Zelei Miao  1   3 , Ke Zhang  1   3 , Luqi Shen  1   4 , Xinxiu Liang  1 , Chun Wang  1 , Haili Zhong  2 , Meng Ye  1   3 , Fengzhe Xu  1   3 , Jun Tang  1   4 , Zengliang Jiang  4   5 , Yue Xi  2 , Yuanqing Fu  1   3 , Yu-Ming Chen  6 , Ju-Sheng Zheng  7   8   9   10
Affiliations

Plasma biomarkers of dairy intake and gut microbiome, and their association with incident carotid plaque: a prospective cohort study

Congmei Xiao et al. BMC Med. .

Abstract

Background: This study aimed to investigate the prospective association of dairy biomarkers of odd-chain saturated fatty acids (OCFA) with incident carotid artery plaque (CAP) and to explore the potential role of gut microbiota and related metabolites in the above associations.

Methods: In the Guangzhou Nutrition and Health Study (GNHS, n = 1211; baseline mean age: 58.7 ± 6.1 years), we investigated the associations of baseline plasma phospholipid OCFAs with CAP incidence and gut microbiota (16S rRNA sequencing) over a median follow-up period of 6.2 years. Westlake Precision Birth Cohort was used to evaluate the potential associations between OCFA and the identified gut microbiota features in a younger population. Associations of OCFAs with CAP, gut microbial alpha diversity, specific genera, and related metabolites were examined using Cox proportional hazards models or linear regression models, with adjustments of potential confounders.

Results: The total OCFA was inversely associated with the incidence of CAP in the GNHS, with a hazard ratio of 0.63 (quartile 4 versus 1: 95% confidence interval [CI]: 0.46, 0.86). Additionally, total OCFA was significantly associated with gut microbial alpha and beta diversity (all P < 0.05). The beta coefficient for the association between total OCFA and the Shannon index was 0.11 (95% CI: 0.06, 0.17). We identified 36 microbial genera significantly associated with total or individual OCFAs (FDR < 0.05). Among these identified genera, the Christensenellaceae R-7 group, an OCFA-positive-related genus, was inversely associated with the prevalence of CAP (P < 0.05). We then identified 13 microbe-derived metabolites significantly associated with both total OCFA and C. R-7 group (FDR < 0.05), including deoxycholic acid and lithocholic acid.

Conclusions: Our results suggest that plasma OCFAs, as objective biomarkers of dairy exposure, are inversely associated with CAP incidence in a Chinese cohort. Further exploration indicates that gut microbiota may be involved in the above association, providing a potential gut microbiota-based intervention target for atherosclerosis.

Keywords: Atherosclerosis; Carotid artery plaque; Carotid intima-media thickness; Dairy biomarker; Gut microbiota; Odd-chain saturated fatty acids.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The GNHS and WeBirth were approved by the Ethics Committee of Westlake University (approval numbers: 20190114ZJS0003 and 20190701ZJS0007). The GNHS was also approved by the Ethics Committee of the School of Public Health at Sun Yat-sen University (approval number: 2018048). Both cohorts were registered at clinicaltrials.gov, with the registration numbers: NCT03179657 for GNHS and NCT04060056 for WeBirth. The written informed consent was obtained for all participants. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
The identified odd-chain saturated fatty acid-related microbiota in the Guangzhou Nutrition and Health Study. A Genus-level PCoA plot between Q4 and Q1 of baseline OCFAs, using Bray–Curtis distance. B Total and individual OCFA-related gut microbiota. C The distribution of OCFA-related gut microbial degree in the co-abundance network. D The correlations among the OCFA-related genera. The sample size was 1119. In B, the bar plot displays the beta coefficients. C used the correlations with FDR < 0.05 to construct the network. In D, we only showed the correlations with an absolute coefficient > 0.3 and FDR < 0.05. OCFA, odd-chain saturated fatty acid; PCoA, principal coordinates analysis
Fig. 2
Fig. 2
The association between total odd-chain saturated fatty acid and the identified microbial genera across cohorts. In the WeBirth cohort, we conducted linear regression models to investigate the cross-sectional associations between total OCFA and the identified genera. The sample size was 605. GNHS, Guangzhou Nutrition and Health Study; OCFA, odd-chain saturated fatty acid; WeBirth, the Westlake Precision Birth Cohort
Fig. 3
Fig. 3
Associations of OCFA-related gut microbial genera with carotid artery plaque and metabolites. A The associations between OCFA-related gut microbiota and the prevalence of CAP. B Associations of C. R-7 group, total OCFA with fecal metabolites. The sample size was 824 for CAP analysis and 661 for microbial metabolites analysis. 7-DHCA, 7-ketodeoxycholic acid; a- and b-MCA, a-muricholic acid and b-muricholic acid; 3-DHCA, 3-oxocholic acid; CAP, carotid artery plaque; GDCA, glycodeoxycholic acid; DCA, deoxycholic acid; GLCA, glycolithocholic acid; HDCA, hyodeoxycholic acid; LCA, lithocholic acid; iso-LCA, iso-lithocholic acid; OCFA, odd-chain saturated fatty acid; 2PP, 2-phenylpropionate; 3PP, hydrocinnamic acid; UDCA, ursodeoxycholic acid
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