The cause-and-effect relationship between gut microbiota abundance and carcinoid syndrome: a bidirectional Mendelian randomization study

Zexin Zhang; Dongting Li; Fengxi Xie; Gulizeba Muhetaer; Haibo Zhang

doi:10.3389/fmicb.2023.1291699

The cause-and-effect relationship between gut microbiota abundance and carcinoid syndrome: a bidirectional Mendelian randomization study

Front Microbiol. 2023 Dec 22:14:1291699. doi: 10.3389/fmicb.2023.1291699. eCollection 2023.

Authors

Zexin Zhang¹, Dongting Li², Fengxi Xie³, Gulizeba Muhetaer¹, Haibo Zhang^{4

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Affiliations

¹ The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China.
² The Affiliated Guangzhou Hospital of TCM of Guangzhou University of Chinese Medicine, Guangzhou, China.
³ Maoming Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China.
⁴ The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
⁵ Guangdong Key Laboratory of Clinical Research of Chinese Medicine, Guangzhou, China.
⁶ Guangdong Joint Laboratory of Guangdong, Hong Kong and Macao Chinese Medicine and Immune Diseases, Guangzhou, China.
⁷ State Key Laboratory of Wet Certificate of Chinese Medicine Jointly Built by the Province and the Ministry, Guangzhou, China.

Abstract

Objective: Carcinoid syndrome (CS) commonly results from neuroendocrine tumors. While active substances are recognized as the main causes of the typical symptoms such as diarrhea and skin flush, the cause-and-effect relationship between gut microbiota abundance and CS remains unclear.

Methods: The Single Nucleotide Polymorphisms (SNPs) related to gut microbiota abundance and CS were obtained from the GWAS summary data. The inverse variance weighted (IVW) method was used to assess the causal relationship between gut microbiota abundance and CS. Additionally, the MR-Egger, Weighted Median model, and Weighted model were employed as supplementary approaches. The heterogeneity function of the TwoSampleMR package was utilized to assess whether SNPs exhibit heterogeneity. The Egger intercept and Presso test were used to assess whether SNPs exhibit pleiotropy. The Leave-One-Out test was employed to evaluate the sensitivity of SNPs. The Steiger test was utilized to examine whether SNPs have a reverse causal relationship. A bidirectional mendelian randomization (MR) study was conducted to elucidate the inferred cause-and-effect relationship between gut microbiota abundance and CS.

Results: The IVW results indicated a causal relationship between 6 gut microbiota taxa and CS. Among the 6 gut microbiota taxa, the genus Anaerofilum (IVW OR: 0.3606, 95%CI: 0.1554-0.8367, p-value: 0.0175) exhibited a protective effect against CS. On the other hand, the family Coriobacteriaceae (IVW OR: 3.4572, 95%CI: 1.0571-11.3066, p-value: 0.0402), the genus Enterorhabdus (IVW OR: 4.2496, 95%CI: 1.3314-13.5640, p-value: 0.0146), the genus Ruminiclostridium6 (IVW OR: 4.0116, 95%CI: 1.2711-12.6604, p-value: 0.0178), the genus Veillonella (IVW OR: 3.7023, 95%CI: 1.0155-13.4980, p-value: 0.0473) and genus Holdemanella (IVW OR: 2.2400, 95%CI: 1.0376-4.8358, p-value: 0.0400) demonstrated a detrimental effect on CS. The CS was not found to have a reverse causal relationship with the above 6 gut microbiota taxa.

Conclusion: Six microbiota taxa were found to have a causal relationship with CS, and further randomized controlled trials are needed for verification.

Keywords: Mendelian randomization study; active substances; carcinoid syndrome; cause-and-effect relationship; gut microbiota abundance.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was funded by the Guangdong Provincial Science and Technology Innovation Strategy Special Fund (Guangdong-Hong Kong-Macau Joint Lab, grant number 2020B1212030006) and Guangzhou University of Traditional Chinese Medicine’s “Double First Class” and high-level university discipline collaborative innovation team: Traditional Chinese Medicine Reverse Lung Cancer Resistance Innovation Team (2021xk60).