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Gut microbiota is involved in the alleviation of loperamide-induced constipation by honey supplementation in mice.

ABSTRACT: Constipation is one of the most common functional gastrointestinal disorders accompanied with intestinal dysbiosis. Laxatives for constipation usually have side effects. Bee honey is a natural food with unique composition, antimicrobial properties, and bifidogenic effect. In order to assess whether honey can ameliorate loperamide-induced constipation in BALB/c mice through the alteration of the gut microbiota, the present study was undertaken. Mice were given Jarrah honey (7.5 g/kg body weight) by gavage once per day for 5 days. Fecal water content, intestinal transit rate together with the colon concentrations of substance P (SP), vasoactive intestinal peptide (VIP), and serotonin (5-hydroxytryptamine; 5-HT) were evaluated. Furthermore, we determined the effect of honey treatment on gut microbiota in mice using stool genomic 16S rRNA sequencing. As a result, honey showed an obvious improvement in fecal water content and alleviated constipation by modulating the microbial composition of the microbiota, and this was highly associated with a proportional decrease in gut Desulfovibrio. In addition, we found that the colon level of neurotransmitters SP and VIP was significantly related to microbial variations. Our results indicate that gut microbiota is involved in the alleviation of loperamide-induced constipation by honey supplementation in mice, and it could be considered as an evaluating parameter in constipation therapy strategies.

SUBMITTER: Li Y

PROVIDER: S-EPMC7455974 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Gut microbiota is involved in the alleviation of loperamide-induced constipation by honey supplementation in mice.

Li Yuyuan Y Long Shangqin S Liu Qiaochu Q Ma Hong H Li Jianxin J Xiaoqing Wei W Yuan Jieli J Li Ming M Hou Binbin B

Food science & nutrition 20200627 8

Constipation is one of the most common functional gastrointestinal disorders accompanied with intestinal dysbiosis. Laxatives for constipation usually have side effects. Bee honey is a natural food with unique composition, antimicrobial properties, and bifidogenic effect. In order to assess whether honey can ameliorate loperamide-induced constipation in BALB/c mice through the alteration of the gut microbiota, the present study was undertaken. Mice were given Jarrah honey (7.5 g/kg body weight) ...[more]

PMID: 32884719

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Project description:Slow transit constipation (STC) is the most common type of functional constipation. Drugs with good effects and few side effects are urgently needed form the treatment of STC. Cymbopogon citratus (DC.) Stapf (CC) is an important medicinal and edible spice plant. The wide range of biological activities suggested that CC may have laxative effects, but thus far, it has not been reported. In this study, the loperamide-induced STC mouse model was used to evaluate the laxative effect of the aqueous extract of CC (CCAE), and the laxative mechanism was systematically explored from the perspectives of the enteric nervous system (ENS), neurotransmitter secretion, gastrointestinal motility factors, intestinal inflammation, gut barrier and gut microbiota. The results showed that CCAE not only decreased the serum vasoactive intestinal polypeptide (VIP), induced nitric oxide synthases (iNOS), and acetylcholinesterase (AchE) in STC mice but also increased the expression of gastrointestinal motility factors in colonic interstitial cells of Cajal (ICCs) and smooth muscle cells (SMCs), thereby significantly shortening the defecation time and improving the gastrointestinal transit rate. The significantly affected gastrointestinal motility factors included stem cell factor receptor (c-Kit), stem cell factor (SCF), anoctamin 1 (Ano1), ryanodine receptor 3 (RyR3), smooth muscle myosin light chain kinase (smMLCK) and Connexin 43 (Cx43). Meanwhile, CCAE could repair loperamide-induced intestinal inflammation and intestinal barrier damage by reducing the expression of the pro-inflammatory factor IL-1β and increasing the expression of the anti-inflammatory factor IL-10, chemical barrier (Muc-2) and mechanical barrier (Cldn4, Cldn12, Occludin, ZO-1, and ZO-2). Interestingly, CCAE could also partially restore loperamide-induced gut microbial dysbiosis in various aspects, such as microbial diversity, community structure and species composition. Importantly, we established a complex but clear network between gut microbiota and host parameters. Muribaculaceae, Lachnospiraceae and UCG-010 showed the most interesting associations with the laxative phenotypes; several other specific taxa showed significant associations with serum neurotransmitters, gastrointestinal motility factors, intestinal inflammation, and the gut barrier. These findings suggested that CCAE might promote intestinal motility by modulating the ENS-ICCs-SMCs network, intestinal inflammation, intestinal barrier and gut microbiota. CC may be an effective and safe therapeutic choice for STC.

Project description:BackgroundConstipation is a common gastrointestinal dysfunction which has a potential impact on people's immune state and their quality of life. Here we investigated the effects of constipation on experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS).MethodsConstipation was induced by loperamide in female C57BL/6 mice. The alternations of gut microbiota, permeability of intestinal barrier and blood-brain barrier, and histopathology of colon were assessed after constipation induction. EAE was induced in the constipation mice. Fecal microbiota transplantation (FMT) was performed from constipation mice into microbiota-depleted mice. Clinical scores, histopathology of inflammation and demyelination, Treg/Th17 and Treg17/Teff17 imbalance both in the peripheral lymphatic organs and central nervous system, cytokines include TGF-β, GM-CSF, IL-10, IL-17A, IL-17F, IL-21, IL-22, and IL-23 in serum were assessed in different groups.ResultsCompared with the vehicle group, the constipation mice showed gut microbiota dysbiosis, colon inflammation and injury, and increased permeability of intestinal barrier and blood-brain barrier. We found that the clinical and pathological scores of the constipation EAE mice were severer than that of the EAE mice. Compared with the EAE mice, the constipation EAE mice showed reduced percentage of Treg and Treg17 cells, increased percentage of Th17 and Teff17 cells, and decreased ratio of Treg/Th17 and Treg17/Teff17 in the spleen, inguinal lymph nodes, brain, and spinal cord. Moreover, the serum levels of TGF-β, IL-10, and IL-21 were decreased while the GM-CSF, IL-17A, IL-17F, IL-22, and IL-23 were increased in the constipation EAE mice. In addition, these pathological processes could be transferred via their gut microbiota.ConclusionsOur results verified that constipation induced gut microbiota dysbiosis exacerbated EAE via aggravating Treg/Th17 and Treg17/Teff17 imbalance and cytokines disturbance in C57BL/6 mice.

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Gut microbiota is involved in the alleviation of loperamide-induced constipation by honey supplementation in mice.

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Gut microbiota is involved in the alleviation of loperamide-induced constipation by honey supplementation in mice.

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