Work

Mendelian randomization of gut microbiota and exploratory testing of preventive effect of commercial Rothia mucilaginosa in constipated mice

Year: 2026

Type: article

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.

Source: Frontiers in Microbiology

DOI: 10.3389/fmicb.2026.1941480

Authors: Peishi Jiang, Xiaoqing Yang, Chenghao Zhang, Yuwei Li, Chen Xu

Institutions: Nankai University, Second Hospital of Tianjin Medical University, Tianjin Medical University, Tianjin University of Traditional Chinese Medicine

Language: English

Topic: Gut microbiota and health

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801