Oral administration of Bifidobacterium bifidum G9-1 alleviates rotavirus gastroenteritis through regulation of intestinal homeostasis by inducing mucosal protective factors

Abstract

Human rotavirus (RV) infection is a leading cause of dehydrating diarrhea in infants and young children worldwide. Since therapeutic approaches to RV gastroenteritis are limited to alleviation of dehydration with oral rehydration solutions, more direct approaches to palliate symptoms of RV gastroenteritis are required. Treatments with probiotics have been increasingly recognized as alternative safe and low cost treatments for moderate infectious diarrhea. In this study, Bifidobacterium bifidum G9-1 (BBG9-1), which has been used as an intestinal drug for several decades, was shown to have a remarkable protective effect against RV gastroenteritis in a suckling mice model. As well as prophylactic oral administration of BBG9-1 from 2 days before RV infection, therapeutic oral administration of BBG9-1 from 1 day after RV infection significantly alleviated RV-induced diarrhea. Therapeutic administration of BBG9-1 reduced various types of damage in the small intestine, such as epithelial vacuolization and villous shortening, and significantly diminished the infectious RV titer in mixtures of cecal contents and feces. It was also shown that therapeutic administration of BBG9-1 significantly increased the number of acidic mucin-positive goblet cells and the gene expression of mucosal protective factors including MUC2, MUC3, MUC4, TGFβ1 and TFF3 in the small intestine. This led to alleviation of low gut permeability shown as decreased gene expression levels of occludin, claudin-1 and villin-1 after RV infection. Furthermore, in the small intestine, therapeutic administration of BBG9-1 significantly palliated the decreased gene expression of SGLT-1, which plays an important role in water absorption. In the large intestine, administered BBG9-1 was shown to replicate to assimilate undigested nutrients, resulting in normalization of the abnormally high osmotic pressure. These results suggested that water malabsorption caused by RV infection was alleviated in mice administered BBG9-1. Thus, the present study showed that oral administration of BBG9-1 palliated diarrhea partly through protection against RV-induced lesions by inducing mucosal protective factors. Oral administration of BBG9-1 is thought to be an efficient method for management of an RV epidemic for both prophylactic and therapeutic purposes.

Effect of probiotic Bifidobacterium bifidum G9-1 on the relationship between gut microbiota profile and stress sensitivity in maternally separated rats

“…BBG9-1 ( Bifidobacterium bifidum G9-1; Biofermin R&D Center, Kobe, Japan) 11 was obtained from the Culture Collection of Biofermin Pharmaceutical Co., Ltd. and cultured at 37 °C for 18 h in GAM Broth (Nissui Pharmaceutical. Co., Ltd., Tokyo, Japan) supplemented with 0.7% glucose and 0.1% Tween 80.…”

“…BBG9-1 isolated from a healthy individual has been used as an intestinal medicine for several decades. Furthermore, we have recently reported that BBG9-1 has a mucosal protective effect against virus-induced enteritis 11 and can attenuates anti-cancer drug-induced inflammation by helping to ameliorate dysbiosis 12 . Accordingly, we were motivated to examine the effect of BBG9-1 in an animal model of IBS.…”

Alteration of Colonic Mucosal Permeability during Antibiotic-Induced Dysbiosis

“…Analysis of the 16S rDNA of the fecal microbiome was performed according to a method described previously [ 28 ] with minor modifications. Briefly, the V3-V4 region of 16S rDNA was amplified using the primers, as reported previously [ 28 ], and then ligated with overhang Illumina adapter consensus sequences.…”

“…Analysis of the 16S rDNA of the fecal microbiome was performed according to a method described previously [ 28 ] with minor modifications. Briefly, the V3-V4 region of 16S rDNA was amplified using the primers, as reported previously [ 28 ], and then ligated with overhang Illumina adapter consensus sequences. The PCR was performed once at 95 °C for 3 min and then for 25 cycles at 95 °C for 30 s, 55 °C for 30 s, and 72 °C for 30 s, and finally at 72 °C for 5 min on a Veriti thermal cycler (Thermo Fisher Scientific, Waltham, MA, USA).…”

Clinical Efficacy Comparison Of Saccharomyces Boulardii And Lactic Acid As Probiotics In Acute Pediatric Diarrhea

“…2,3 In underdeveloped countries, enteric bacteria such as Escherichia coli, Campylobacter, Shigella, Vibrio cholerae, Salmonella, viruses such as Rotavirus, Human caliciviruses, and parasites like Cryptosporidium parvum, Giardia intestinalis, Entamoeba histolytica, Cyclosporacayetanensis are major pathogens to cause diarrhea. [4][5][6] Diarrhea results in higher amount of water losses that may lead to death, if left untreated. 1 Oral rehydration solutions (ORS) have been found to decrease the incidence of mortality and morbidity caused by diarrhea; but ORS did not have any effect on the duration of the disease, consistency of the stools, and gastrointestinal flora.…”