Mendelian randomization of gut microbiota and exploratory testing of preventive effect of commercial Rothia mucilaginosa in constipated mice
6 affiliations
- 1Department of Colorectal Surgery, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University, Nankai University, Tianjin, China
- 2School of Medicine, Nankai University, Tianjin, China
- 3Tianjin Institute of Urology, The 2nd Hospital of Tianjin Medical University, Tianjin Medical University, Tianjin, China
- 4The Institute of Translational Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, China
- 5Tianjin Institute of Coloproctology, Tianjin, China
- 6Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, China
Abstract
Constipation is linked to gut microbiota dysbiosis, but causal microbial contributors and tractable bacterial interventions remain incompletely defined. This study first performed two-sample Mendelian randomization using Dutch Microbiome Project gut-microbiome Genome-Wide Association Study (GWAS) data (N = 7,738) and a European constipation GWAS (N = 411,623) to identify gut taxa linked to constipation. Then, in vitro metabolomics and a loperamide-induced constipation mouse model were used in male C57BL/6 mice to exploratorily test whether the commercial Rothia mucilaginosa strain BNCC363031 prevents loperamide-induced constipation. In an exploratory two-sample MR screen across 207 gut taxa, genetically predicted Rothia was nominally associated with lower constipation risk [odds ratio (OR) = 0.916, p = 0.0041], and the species-level Rothia mucilaginosa showed a concordant nominal protective association (OR = 0.921, p = 0.0232). In mice (n = 8 per group), preventive gavage partially restored loperamide-suppressed defecation: the cross-day mean fecal pellet count in the last 3 h per day was higher in the Rothia mucilaginosa group (RG) than in model controls (MCs) (7.94 vs. 4.41; p = 0.0306) but lower than in normal controls (NCs) (13.16; p = 0.00162), whereas body weight; small-intestinal transit; and immunohistochemical zonula occludens-1 (ZO-1), Claudin-1, and mucin 2 (MUC2) H-scores were unchanged. A fecal 16S V4 signal corresponding to R. mucilaginosa was detected at a very low abundance in only 2/8 RG mice; in vitro metabolomics identified candidates of secreted metabolites, including acetic acid. This study provides a reference for research on Rothia mucilaginosa in the context of constipation.
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BibTeX
@article{jiang2026mendelian,
title = {{Mendelian randomization of gut microbiota and exploratory testing of preventive effect of commercial Rothia mucilaginosa in constipated mice}},
author = {Peishi Jiang and Xiaoqing Yang and Chenghao Zhang and Yuwei Li and Chen Xu},
journal = {Frontiers in Microbiology},
year = {2026},
month = oct,
doi = {10.3389/fmicb.2026.1941480},
url = {https://doi.org/10.3389/fmicb.2026.1941480},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Mendelian randomization of gut microbiota and exploratory testing of preventive effect of commercial Rothia mucilaginosa in constipated mice
AU - Peishi Jiang
AU - Xiaoqing Yang
AU - Chenghao Zhang
AU - Yuwei Li
AU - Chen Xu
PY - 2026
DA - 2026/10/12
JO - Frontiers in Microbiology
DO - 10.3389/fmicb.2026.1941480
UR - https://doi.org/10.3389/fmicb.2026.1941480
AB - Constipation is linked to gut microbiota dysbiosis, but causal microbial contributors and tractable bacterial interventions remain incompletely defined. This study first performed two-sample Mendelian randomization using Dutch Microbiome Project gut-microbiome Genome-Wide Association Study (GWAS) data (N = 7,738) and a European constipation GWAS (N = 411,623) to identify gut taxa linked to constipation. Then, in vitro metabolomics and a loperamide-induced constipation mouse model were used in male C57BL/6 mice to exploratorily test whether the commercial Rothia mucilaginosa strain BNCC363031 prevents loperamide-induced constipation. In an exploratory two-sample MR screen across 207 gut taxa, genetically predicted Rothia was nominally associated with lower constipation risk [odds ratio (OR) = 0.916, p = 0.0041], and the species-level Rothia mucilaginosa showed a concordant nominal protective association (OR = 0.921, p = 0.0232). In mice (n = 8 per group), preventive gavage partially restored loperamide-suppressed defecation: the cross-day mean fecal pellet count in the last 3 h per day was higher in the Rothia mucilaginosa group (RG) than in model controls (MCs) (7.94 vs. 4.41; p = 0.0306) but lower than in normal controls (NCs) (13.16; p = 0.00162), whereas body weight; small-intestinal transit; and immunohistochemical zonula occludens-1 (ZO-1), Claudin-1, and mucin 2 (MUC2) H-scores were unchanged. A fecal 16S V4 signal corresponding to R. mucilaginosa was detected at a very low abundance in only 2/8 RG mice; in vitro metabolomics identified candidates of secreted metabolites, including acetic acid. This study provides a reference for research on Rothia mucilaginosa in the context of constipation.
SN - 1664-302X
ER -