Kazunari Ushida

Health‐beneficial effects of probiotics: Its mode of action

It is now widely recognized that probiotics have health-beneficial effects on humans and animals. Probiotics should survive in the intestinal tract to exert beneficial effects on the hosts health. To keep a sufficient level of probiotic bacteria in the gastrointestinal tract, a shorter interval between doses may be required. Although adherence to the intestinal epithelial cell and mucus is not a universal property of probiotics, high ability to adhere to the intestinal surface might strongly interfere with infection of pathogenic bacteria and regulate the immune system. The administration of probiotic Lactobacillus stimulated indigenous Lactobacilli and the production of short-chain fatty acids. This alteration of the intestinal environment should contribute to maintain the hosts health. The immunomodulatory effects of probiotics are related to important parts of their beneficial effects. Probiotics may modulate the intestinal immune response through the stimulation of certain cytokine and IgA secretion in intestinal mucosa. The health-beneficial effects, in particular the immunomodulation effect, of probiotics depend on the strain used. Differences in indigenous intestinal microflora significantly alter the magnitude of the effects of a probiotic. Specific probiotic strains suitable for each animal species and their life stage as well as each individual should be found.

Voluntary Running Exercise Alters Microbiota Composition and Increases n-Butyrate Concentration in the Rat Cecum

The effects of voluntary wheel-running exercise on cecal microbiota and short-chain fatty acid production were investigated in rats. The microbiota composition was notably different between the exercised and sedentary rats. Furthermore, the exercised rats showed a significantly higher n-butyrate concentration than the sedentary rats. This alteration of the cecal microbial environment may contribute to the beneficial effect of exercise on gastrointestinal disorders.

Improvement of nutritional status and incidence of infection in hospitalised, enterally fed elderly by feeding of fermented milk containing probiotic Lactobacillus johnsonii La1 (NCC533)

Probiotics have potential to improve host immunity; however, there is less evidence showing their efficacy against infections and nutritional status in the elderly. We conducted a double-blinded feeding trial in the elderly to elucidate the effect of fermented milk containing Lactobacillus johnsonii La1 (LC1) on infections and nutritional status. Twenty-four completely enterally fed elderly in-patients aged over 70 years were randomly assigned into two groups. All subjects were administered 3768 kJ (900 kcal)/d of total enteral nutrition (EN) through tube feeding for 12 weeks. Subjects in the LC1 group were administered 373 kJ (89 kcal)/d of LC1 fermented milk after feeding of 3395 kJ (811 kcal)/d of EN for 12 weeks. In the control group, 373 kJ/d of the same EN was replaced from the fermented milk. In the LC1 group, the percentage of days with infections during the run-in observation period was 15.4 (SD 17.3) %, which significantly decreased to 5.7 (SD 8.1) % during the intervention period (P = 0.018), and the reduction was larger than that of the control group (P = 0.047). Blood Hb increased (P < 0.05), and there was a tendency towards an increase in serum albumin and a decrease in TNF-alpha (a pro-inflammatory cytokine) in the LC1 group. There was a trend towards an increase in blood phagocytic activity (a natural immunity marker) in the subjects whose initial level was low in the LC1 group. There were no changes in those parameters in the control group. Administration of fermented milk containing the probiotic L. johnsonii La1 may contribute to suppressing infections by improving nutritional and immunological status in the elderly.

Comparative expression of hexose transporters (SGLT1, GLUT1, GLUT2 and GLUT5) throughout the mouse gastrointestinal tract

Hexose transporters play a pivotal role in the absorption of food-derived monosaccharides in the gastrointestinal tract. Although a basic knowledge of the hexose transporters has already been gained, their detailed distribution and comparative intensities of expression throughout the gastrointestinal tract have not been fully elucidated. In this study, we quantitatively evaluated the expression of SGLT1, GLUT1, GLUT2, and GLUT5 by in situ hybridization and real-time PCR techniques using a total of 28 segments from the gastrointestinal tract of 9-week-old mice. GLUT2 and GLUT5 mRNA expressions were detected predominantly from the proximal to middle parts of the small intestine, showing identical expression profiles, while SGLT1 mRNA was expressed not only in the small intestine but also in the large intestine. Notably, GLUT1 mRNA was expressed at a considerable level in both the stomach and large intestine but was negligible in the small intestine. Immunohistochemistry demonstrated the polarized localization of hexose transporters in the large intestine: SGLT1 on the luminal surface and GLUT1 on the basal side of epithelial cells. The present study provided more elaborate information concerning the localization of hexose transporters in the small intestine. Furthermore, this study revealed the significant expression of glucose transporters in the large intestine, suggesting the existence of the physiological uptake of glucose in that location in mice.

Oral treatment with probiotic Lactobacillus johnsonii NCC533 (La1) for a specific part of the weaning period prevents the development of atopic dermatitis induced after maturation in model mice, NC/Nga

Background  The inhibitory effect of probiotic bacteria on atopic dermatitis has been shown in human infants, but the mechanism is still unclear.

Vertical and horizontal transmission of intestinal commensal bacteria in the rat model

The intestinal microbiota of 10 pups (five from dam A and five from dam B) in the suckling stage (18 days old) and at maturity (40 days old) were compared with those of their dams to assess the mechanisms of bacterial transmission during development of intestinal microbiota in the rat model. Fecal samples were subjected to amplified ribosomal DNA restriction analysis and 65 operational taxonomic units (OTUs) were identified. The intestinal microbiota of mature pups were more complex than those of the suckling stage. Most of the OTUs present in dams were detected in their pups at maturity. These common OTUs accounted for more than 70% of the clones of libraries generated from both groups of pups. In contrast, the number of OTUs in pups that were not shared by their dams was larger than the number they had in common. These bacteria were presumably transmitted horizontally from environmental sources. However, these OTUs accounted for less than 30% of the clones generated from both groups of pups. This study suggested that vertically transmitted bacteria were the predominant component of the intestinal microbiota of pups, although the diversity of intestinal microbiota during pup growth was influenced by horizontal transmission.

Oral administration of Lactobacillus plantarum Lq80 and Megasphaera elsdenii iNP-001 induces efficient recovery from mucosal atrophy in the small and the large intestines of weaning piglets.

Weaning causes atrophy of intestinal mucosa and a drop of IgA protection in piglets which increases vulnerability to pathogenic infections. Probiotic lactobacilli may support recovery from such weaning stresses. Butyrate-produce bacteria may support the growth of colonic mucosa. Megasphaera elsdenii, a lactate-utilizing butyrate producer, may help butyrate production particularly when combined with lactobacilli. Weaned piglets (Experiment 1: 20 days old, Experiment 2: 28 days old) were orally dosed once a day with either (L) 10(10) (cell/dose) L. plantarum Lq80, or (LM) 10(10) (cell/dose) Lq80 with 10(9) (cell/dose) M. elsdenii iNP-001. Lq80 was contained in capsules resistant to gastric digestion. M. elsdenii was contained in capsules resistant to gastric and intestinal digestion. An untreated control (C) was also prepared. After 2 weeks of administration, L. plantarum enhanced the recovery from the villous atrophy in both experiments. The rectal and colonic IgA tended to be higher in L and LM than in C in Experiment 1. Colonic butyrate was higher in LM than in the others in Experiment 1. The thickness of the colonic mucosa was greater in LM than in the others in Experiment 1. In early weaned piglets, the effects of L. plantarum and M. elsdenii were clear.

The composition of intestinal bacteria affects the level of luminal IgA.

An essential role of several specific intestinal bacteria in the intestinal IgA level is suggested. Fecal IgA concentration in mice from one breeder was significantly higher than that in mice from two other breeders. The level of segmented filamentous bacteria and four particular clostridia in mice from the former breeder are of particular importance in developing the IgA production and secretion system.

Effects of administration of Bifidobacterium animalis subsp. lactis GCL2505 on defecation frequency and bifidobacterial microbiota composition in humans.

The aim of this study was to evaluate the changes in endogenous bifidobacteria and administered Bifidobacterium animalis subsp. lactis (B. lactis) GCL2505 (GCL2505) in the intestine after administration of GCL2505 by means of a randomized, placebo-controlled double-blind, cross-over study. An increase in the number of total bifidobacteria (the sum of B. bifidum, B. breve, B. longum subsp. longum, B. adolescentis, B. anglatum, B. catenulatum, B. pseudocatenulatum, B. dentium, B. longum subsp. infantis and B. lactis) in the feces were observed after administration of GCL2505 using species- and subspecies-specific real-time polymerase chain reaction analysis. However, the number of endogenous bifidobacteria species (excluding B. lactis) remained unchanged. B. lactis also became the predominant bifidobacterial species. Taking into account the number of GCL2505 administered, the findings further suggested that GCL2505 proliferated in the intestine. In addition, the defecation frequency increased during GCL2505 administration compared with the placebo. Moreover, a single administration study (n=17) clearly demonstrated that GCL2505 successfully reached the intestine before proliferating at least 10-fold. This is the first report to show an increase in intestinal bifidobacteria, with no changes to the endogenous species, and improvements in constipation following proliferation of administered bifidobacteria.

Bifidobacterium moukalabense sp. nov., isolated from the faeces of wild west lowland gorilla (Gorilla gorilla gorilla).

Gram-staining-positive anaerobic rods were isolated from the faeces of a wild lowland gorilla (Gorilla gorilla gorilla) in Moukalaba-Doudou National Park, Gabon, and strain GG01(T) was taxonomically investigated. Based on phylogenetic analyses and specific phenotypic characteristics, the strain belonged to the genus Bifidobacterium. Phylogenetic analysis of its 16S rRNA gene sequence revealed that strain GG01(T) formed a single monophyletic cluster and had a distinct line of descent. Based on 16S rRNA gene sequence similarity, the type strains of Bifidobacterium catenulatum JCM 1194(T) (98.3%) and Bifidobacterium pseudocatenulatum (98.1%) JCM 1200(T) were the most closely related to this novel strain, although it was clear that they belonged to different species. hsp60 sequences also supported these relationships. The DNA G+C content of this novel strain was 60.1 mol%. Bifidobacterium moukalabense sp. nov. (type strain GG01(T) = JCM 18751(T) = DSM 27321(T)) is proposed.