Multi-strain probiotics alleviate loperamide-induced constipation by adjusting the microbiome, serotonin, and short-chain fatty acids in rats

Jin-Ju Jeong; Raja Ganesan; Yoo-Jeong Jin; Hee Jin Park; Byeong Hyun Min; Min Kyo Jeong; Sang Jun Yoon; Mi Ran Choi; Jieun Choi; Ji Hyun Moon; Uigi Min; Jong-Hyun Lim; Do Yup Lee; Sang Hak Han; Young Lim Ham; Byung-Yong Kim; Ki Tae Suk

doi:10.3389/fmicb.2023.1174968

Multi-strain probiotics alleviate loperamide-induced constipation by adjusting the microbiome, serotonin, and short-chain fatty acids in rats

Front Microbiol. 2023 Jun 2:14:1174968. doi: 10.3389/fmicb.2023.1174968. eCollection 2023.

Authors

Jin-Ju Jeong¹, Raja Ganesan¹, Yoo-Jeong Jin², Hee Jin Park¹, Byeong Hyun Min¹, Min Kyo Jeong¹, Sang Jun Yoon¹, Mi Ran Choi¹, Jieun Choi³, Ji Hyun Moon³, Uigi Min², Jong-Hyun Lim², Do Yup Lee³, Sang Hak Han⁴, Young Lim Ham⁵, Byung-Yong Kim², Ki Tae Suk¹

Affiliations

¹ Institute for Liver and Digestive Disease, Hallym University, Chuncheon, Republic of Korea.
² R&D Center, Chong Kun Dang Healthcare, Seoul, Republic of Korea.
³ Department of Agricultural Biotechnology, Center for Food and Bioconvergence, Research Institute of Agricultural and Life Sciences, Seoul National University, Seoul, Republic of Korea.
⁴ Department of Pathology, Hallym University College of Medicine, Chuncheon, Republic of Korea.
⁵ Department of Nursing, Daewon University College, Jecheon, Republic of Korea.

Abstract

Constipation is one of the most common gastrointestinal (GI) disorders worldwide. The use of probiotics to improve constipation is well known. In this study, the effect on loperamide-induced constipation by intragastric administration of probiotics Consti-Biome mixed with SynBalance® SmilinGut (Lactobacillus plantarum PBS067, Lactobacillus rhamnosus LRH020, Bifidobacterium animalis subsp. lactis BL050; Roelmi HPC), L. plantarum UALp-05 (Chr. Hansen), Lactobacillus acidophilus DDS-1 (Chr. Hansen), and Streptococcus thermophilus CKDB027 (Chong Kun Dang Bio) to rats was evaluated. To induce constipation, 5 mg/kg loperamide was intraperitoneally administered twice a day for 7 days to all groups except the normal control group. After inducing constipation, Dulcolax-S tablets and multi-strain probiotics Consti-Biome were orally administered once a day for 14 days. The probiotics were administered 0.5 mL at concentrations of 2 × 10⁸ CFU/mL (G1), 2 × 10⁹ CFU/mL (G2), and 2 × 10¹⁰ CFU/mL (G3). Compared to the loperamide administration group (LOP), the multi-strain probiotics not only significantly increased the number of fecal pellets but also improved the GI transit rate. The mRNA expression levels of serotonin- and mucin-related genes in the colons that were treated with the probiotics were also significantly increased compared to levels in the LOP group. In addition, an increase in serotonin was observed in the colon. The cecum metabolites showed a different pattern between the probiotics-treated groups and the LOP group, and an increase in short-chain fatty acids was observed in the probiotic-treated groups. The abundances of the phylum Verrucomicrobia, the family Erysipelotrichaceae and the genus Akkermansia were increased in fecal samples of the probiotic-treated groups. Therefore, the multi-strain probiotics used in this experiment were thought to help alleviate LOP-induced constipation by altering the levels of short-chain fatty acids, serotonin, and mucin through improvement in the intestinal microflora.

Keywords: SCFAs; constipation; microbiome; probiotics; serotonin.