Causal effect of gut microbiota of Defluviitaleaceae on the clinical pathway of "Influenza-Subacute Thyroiditis-Hypothyroidism"

Xin Zhang; Pei-Heng Li; Dongyue Wang; Hancong Li; Xiangyu Kong; Gongshuang Zhang; Yue Zhao; Jiaye Liu; Wenshuang Wu; Yuwei Zhang; Zhi-Hui Li; Han Luo

doi:10.3389/fmicb.2024.1354989

Causal effect of gut microbiota of Defluviitaleaceae on the clinical pathway of "Influenza-Subacute Thyroiditis-Hypothyroidism"

Front Microbiol. 2024 Feb 26:15:1354989. doi: 10.3389/fmicb.2024.1354989. eCollection 2024.

Authors

Xin Zhang^#^{1

2}, Pei-Heng Li^#³, Dongyue Wang^#⁴, Hancong Li³, Xiangyu Kong³, Gongshuang Zhang³, Yue Zhao³, Jiaye Liu³, Wenshuang Wu³, Yuwei Zhang^{5

6}, Zhi-Hui Li³, Han Luo^{3

7}

Affiliations

¹ Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
² Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
³ Division of Thyroid Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
⁴ Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, China.
⁵ Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu, China.
⁶ Center for Diabetes and Metabolism Research, West China Hospital of Sichuan University, Chengdu, China.
⁷ Department of Laboratory Medicine/Research Centre of Clinical Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

^# Contributed equally.

Abstract

Introduction: Hypothyroidism has been found to be influenced by gut microbiota. However, it remains unclear which a taxon of gut microbiota plays a key role in this function. Identifying the key bacteria affects hypothyroidism and through what mechanism will be helpful for the prevention of hypothyroidism through specific clinical pathways.

Materials and methods: In Study A, 35 families and 130 genera of gut microbiota are used as exposures, with hypothyroidism as the outcome. The causal effect of the gut microbiota on hypothyroidism is estimated through two-sample Mendelian randomization. Combining the results of the two taxonomical levels, key taxa are selected, which in Study B are investigated for their causal association with multiple generally admitted causes of hypothyroidism and their more upstream factors. For validating and revealing the potential mechanism, enrichment analyses of the related genes and interacting transcription factors were performed.

Results: In Study A, Defluviitaleaceae (OR: 0.043, 95% CI: 0.005-0.363, P = 0.018)/Defluviitaleaceae_UCG_011 (OR: 0.385, 95% CI: 0.172-0.865, P = 0.021) are significantly causally associated with hypothyroidism at both taxonomical levels. In Study B, Defluviitaleaceae family and Defluviitaleaceae_UCG_011 genus show the causal association with decreased thyroiditis (Family: OR: 0.174, 95% CI: 0.046-0.653, P = 0.029; Genus: OR: 0.139, 95% CI: 0.029-0.664, P = 0.043), decreased subacute thyroiditis (Family: OR: 0.028, 95% CI: 0.004-0.213, P = 0.007; Genus: OR: 0.018, 95% CI: 0.002-0.194, P = 0.013), decreased influenza (Family: OR: 0.818, 95% CI: 0.676-0.989, P = 0.038; Genus: OR: 0.792, 95% CI: 0.644-0.974, P = 0.027), and increased anti-influenza H3N2 IgG levels (Family: OR: 1.934, 95% CI: 1.123-3.332, P = 0.017; Genus: OR: 1.675, 95% CI: 0.953-2.943, P = 0.073). The results of the enrichment analysis are consistent with the findings and the suggested possible mechanisms.

Conclusion: Defluviitaleaceae of the gut microbiota displays the probability of causally inhibiting the clinical pathway of "Influenza-Subacute Thyroiditis-Hypothyroidism" and acts as the potential probiotics to prevent influenza, subacute thyroiditis, and hypothyroidism.

Keywords: Mendelian randomization; gut microbiota; hypothyroidism; influenza; subacute thyroiditis.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. We received funding from the Sichuan Science and Technology Program (2023YFS0098, 2023YFG0278, and 2023YFS0113); the Clinical Research Incubation Project, West China Hospital, Sichuan University (22HXFH019); the Post-Doctor Research Project, West China Hospital, Sichuan University (2021HXBH054); the Sichuan University postdoctoral interdisciplinary Innovation Fund; the Natural Science Foundation of Sichuan Province (2023NSFSC1851); and China Postdoctoral Science Foundation (2023M732446).