In children with cow's milk allergy, 1-kestose affects the gut microbiota and reaction threshold.

BACKGROUND: Interventions targeting the gut microbiota for treating food allergy (FA) have been gaining much attention. Although several studies have examined the effects of probiotics, few have verified the effects of prebiotic intervention on FA in humans. METHODS: We conducted a preliminary open-label, parallel-group comparison trial in children diagnosed with severe cow's milk allergy (CMA) who were instructed to ingest baked milk (BM; bread or cookies) daily. The subjects either received or did not receive the prebiotic 1-kestose (kestose) daily for 6 months. CMA symptoms and the threshold dose for milk protein were evaluated by oral food challenge with heated milk or BM. Blood and fecal samples were also collected for investigations of the antigen-specific immunoglobulin (Ig) E levels and microbiota composition. RESULTS: Kestose treatment significantly increased the threshold dose for milk protein, and decreased the milk- and casein-specific IgE levels in serum. In those treated with kestose, the abundance of Fusicatenibacter spp. significantly increased in the feces, and a significant inverse correlation was seen between the abundance of Fusicatenibacter spp. and the milk- and casein-specific IgE levels. CONCLUSION: Kestose treatment induced some tolerance to milk protein via changes in the gut microbiota composition in children with FA. IMPACT: A 6-month treatment with the prebiotic kestose increased the threshold dose for milk protein, and decreased the serum levels of milk- and casein-specific IgE in children diagnosed with cow's milk allergy. The kestose treatment increased the abundance of Fusicatenibacter spp. in the gut, which was inversely correlated with the antigen-specific IgE levels. This is the first study to demonstrate that a prebiotic intervention induced some tolerance to an allergen in children with food allergy.

Microbiota in the stomach and application of probiotics to gastroduodenal diseases.

The stomach is a hostile environment for most microbes because strong gastric acid kills indigenous microorganisms. Thus, the mass of indigenous microbes detected by traditional culturing method in a highly acidic stomach is reported to be very small. However, in a stomach with less acidity due to atrophic changes of the gastric mucosa, the number of live gastric microbiota dramatically increases and their composition changes. A probiotic is defined as a live microorganism that, when administered in adequate amounts, confers a health benefit on the host. The administration of probiotics to the stomach has thus far been considered impractical, mainly due to the strong acidity in the stomach. The identification of candidate probiotic strains with sufficient resistance to acidity and the ability to achieve close proximity to the gastric mucosa could enable the application of probiotics to the stomach. The utilization of probiotics alone for Helicobacter pylori (H. pylori) infection significantly improves gastric mucosal inflammation and decreases the density of H. pylori on the mucosa, although complete eradication of H. pylori has not yet been demonstrated. The use of probiotics in combination with antimicrobial agents significantly increases the H. pylori eradication rate, especially when the H. pylori strains are resistant to antimicrobial agents. While H. pylori has been considered the most important pathogenic bacterium for the development of gastric cancer, bacteria other than H. pylori are also suggested to be causative pathogens that promote the development of gastric cancer, even after the eradication of H. pylori. Increased non-H. pylori Gram-negative bacteria in the stomach with weak acidity accompanying atrophic gastritis may perpetuate gastric mucosal inflammation and accelerate carcinogenic progression, even after H. pylori eradication. Probiotics restore the acidity in this stomach environment and may therefore prevent the development of gastric cancer by termination of Gram-negative bacteria-induced inflammation. Functional dyspepsia (FD) is defined as the presence of symptoms that are thought to originate in the gastroduodenal region in the absence of any organic, systematic or metabolic diseases. Accumulating evidence has pointed out the duodenum as a target region underlying the pathophysiology of FD. A randomized placebo-controlled clinical trial using a probiotic strain (LG21) demonstrated a significant improving effect on major FD symptoms. One of the possible mechanisms of this effect is protection of the duodenal mucosa from injurious intestinal bacteria through the resolution of small intestinal bacterial over growth.

Effect of gut microbiota early in life on aggressive behavior in mice.

Recent reports have indicated that gut microbiota modulates the responses to stress through the microbiota-gut-brain axis in mice, suggesting a connection between gut microbiota and brain function. We hypothesized that the gut microbiota early in life would have an effect on aggressiveness, and examined how gut microbiota affect aggressive behaviors in mice. BALB/c mice were housed in germ-free (GF) and ex-germ-free (Ex-GF) isolators. An aggression test was performed between castrated and a non-castrated mice at 8 weeks of age; the mice were allowed to confront each other for 10 min in strictly contamination-free environments. To evaluate aggressive behavior related to gut microbiota, we orally administered diluted Ex-GF mouse feces to the offspring of GF mice at 0, 6, and 10 weeks. GF mice showed more aggression than Ex-GF mice. Furthermore, GF mice who were administered feces of the Ex-GF group at 0-week-old were less aggressive than the GF mice. These findings suggested that the gut microbiota in the early stages of development was likely to have an effect on aggressiveness. Maintenance of healthy gut microbiota early in life can affect the mitigation of aggressive behavioral characteristics throughout the lifetime.

Increase in the Lipopolysaccharide Activity and Accumulation of Gram-Negative Bacteria in the Stomach With Low Acidity.

INTRODUCTION: Lipopolysaccharides (LPSs) of Gram-negative bacteria (GNB) are highly toxic and induce inflammation. Therefore, we investigated both the LPS activity and composition of GNB in the gastric fluid (GF) to assess the potential toxicity of them accumulated in the stomach. METHODS: GF and saliva samples were obtained from 158 outpatients who were undergoing upper gastrointestinal endoscopy and 36 volunteers using a nasogastric tube. The LPS activity was measured by assay kits including recombinant Factor C or Limulus amebocyte lysate. To assess the bacterial composition in the samples, a 16S ribosomal DNA-based operational taxonomic unit analysis was performed. We focused on the genera representing >0.1% of the whole microbiota. RESULTS: We found a high LPS activity in the GF samples with weak acidity (approximately > pH 4), whereas little/no activity in those with strong acidity (approximately < pH 2). Spearman test also demonstrated a close correlation between pH and LPS in those samples (r = 0.872). The relative abundance of GNB in the saliva showed no significant difference between the subject groups with weak- and strong-acidity GF. In addition, in the subjects whose GF acidity was weak, the GNB abundance in the GF was almost the same as that in the saliva. By contrast, in the subjects whose GF acidity was strong, the GNB abundance in the GF was significantly lower than that in the saliva. DISCUSSION: GNB that have recently moved from the oral cavity might account for the prominent LPS activity in a stomach with weak acidity.

Activation of butyrate-producing bacteria as well as bifidobacteria in the cat intestinal microbiota by the administration of 1-kestose, the smallest component of fructo-oligosaccharide.

1-kestose is a structural component of fructo-oligosaccharides and is composed of 2 fructose residues bound to sucrose through ß2-1 bonds. In the present study, the influence of the ingestion of 1-kestose on the intestinal microbiota was investigated in cats. Six healthy cats were administered 1 g/day of 1-kestose for 8 weeks followed by a 2-week wash-out period. Fecal samples were collected from cats after 0, 4, 8, and 10 weeks. The intestinal microbiota was examined by a 16S rRNA gene metagenomic analysis and real-time PCR. Short-chain fatty acids were measured by GC/MS. The results suggested that the intestinal bacterial community structure in feline assigned to this study was divided into 2 types: one group mainly composed of the genus Lactobacillus (GA) and the other mainly composed of the genus Blautia with very few bacteria of Lactobacillus (GB). Furthermore, the number of Bifidobacterium slightly increased after the administration of 1-kestose (at 4 and 8 weeks) (P<0.1). The administration of 1-kestose also increased the abundance of Megasphaera, the butyric acid-producing bacteria, at 4 and 8 weeks (P<0.1). Furthermore, an increase in butyric acid levels was observed after the administration of 1-kestose for 4 weeks (P<0.1). These results suggest that 1-kestose activated butyrate-producing bacteria as well as bifidobacteria and propose its potential as a new generation prebiotic.

Probiotic L. gasseri strain (LG21) for the upper gastrointestinal tract acting through improvement of indigenous microbiota.

OBJECTIVE: To describe probiotics including a Lactobacillus gasseri strain LG21 used for the upper gastrointestinal tract, which are considered to act through improvement of indigenous microbiota inhabiting there. BACKGROUND AND DESIGN: Because the early definition of probiotics emphasized their effects on improving the intestinal microbial ecology, their effects on the intestinal tract and its immunity have been considered common general benefits associated with probiotics. This conclusion was also based on a body of successful clinical trials whose endpoints were the prevention or treatment of intestinal diseases. In contrast to intestinal microbiota, our understanding of the role of gastric microbiota in human health and physiology remains poor, as the bacterial load in the stomach is considered too small to exert a significant effect due to the highly acidic environment of the human stomach. Therefore, the intervention using probiotics in the stomach is still limited at present.Results:In this article using representative 38 quoted articles, we first describe the gastric microbiota, as the indigenous microbiota in the stomach is thought to be significantly involved in the pathophysiology of this organ, since probiotics exert their beneficial effects through improving the resident microbiota. We then review the present status and future prospects of probiotics for the treatment of upper gastrointestinal diseases by quoting representative published articles, including our basic and clinical data. CONCLUSIONS: Probiotics have been demonstrated to suppress Helicobacter pylori in the stomach, and are also expected to improve functional dyspepsia through the correction of dysbiotic gastric microbiota.

The Gut Microbiome Derived From Anorexia Nervosa Patients Impairs Weight Gain and Behavioral Performance in Female Mice.

Anorexia nervosa (AN) results in gut dysbiosis, but whether the dysbiosis contributes to AN-specific pathologies such as poor weight gain and neuropsychiatric abnormalities remains unclear. To address this, germ-free mice were reconstituted with the microbiota of four patients with restricting-type AN (gAN mice) and four healthy control individuals (gHC mice). The effects of gut microbes on weight gain and behavioral characteristics were examined. Fecal microbial profiles in recipient gnotobiotic mice were clustered with those of the human donors. Compared with gHC mice, gAN mice showed a decrease in body weight gain, concomitant with reduced food intake. Food efficiency ratio (body weight gain/food intake) was also significantly lower in gAN mice than in gHC mice, suggesting that decreased appetite as well as the capacity to convert ingested food to unit of body substance may contribute to poor weight gain. Both anxiety-related behavior measured by open-field tests and compulsive behavior measured by a marble-burying test were increased only in gAN mice but not in gHC mice. Serotonin levels in the brain stem of gAN mice were lower than those in the brain stem of gHC mice. Moreover, the genus Bacteroides showed the highest correlation with the number of buried marbles among all genera identified. Administration of Bacteroides vulgatus reversed compulsive behavior but failed to exert any substantial effect on body weight. Collectively, these results indicate that AN-specific dysbiosis may contribute to both poor weight gain and mental disorders in patients with AN.

1-Kestose, the Smallest Fructooligosaccharide Component, Which Efficiently Stimulates Faecalibacterium prausnitzii as Well as Bifidobacteria in Humans.

The concept of prebiotics was established more than 30 years ago. While the prebiotic concept has now expanded thus includes non-carbohydrate substances and diverse categories other than foods, fructooligosaccharides (FOS) have still predominantly been used as pebiotics, because the effects of FOS exclusively act through the enrichment of Bifidobacterium and Lactobacillus spp., which have been classified as beneficial intestinal commensals so far. Now the commercially available FOS products are synthetic mixture of several kinds of FOS components including 1-kestose (GF2), nystose (GF3) and GF4. In our previous studies, superiority of 1-kestose to the longer-chain FOS components such as nystose with regard to bifidogenic activity was clearly demonstrated. Recently, a broader range of beneficial bacteria including butyrate-producing indigenous bacteria have been recognized and expected to be new probiotic strains. Among them, resident Faecalibacterium prausnitzii is a butyrate producer with a significant anti-inflammatory effect thus expected to be useful as a next-generation probiotic. However, this bacterium is extremely oxygen-sensitive thus can be difficult to grow industrially. On the other hand, we have clearly demonstrated a significant prebiotic effect of 1-kestose, which is the smallest component of FOS, on F. prausnitzii in the gut of humans. These findings suggest that 1-kestose has impressive potential as a new prebiotic targeting F. prausnitzii, a next-generation probiotic strain, as well as bifidobacteria.

Changes in the gut microbiota composition and the plasma ghrelin level in patients with Helicobacter pylori-infected patients with eradication therapy.

OBJECTIVE: To investigate the influence of antimicrobials on both the gut microbiota structure and the plasma ghrelin level using Helicobacter pylori-infected patients who underwent eradication therapy. DESIGN: Twenty H. pylori-infected patients (mean age 68.3 years old) who underwent eradication therapy participated in the study. For the therapy, patients had 1 week of triple therapy consisting of amoxicillin, clarithromycin and proton-pump inhibitors. Stool and blood samples were obtained before (S1), immediately after (S2) and/or 3 months after (S3) the therapies. The concentrations of ghrelin and leptin in the blood were assayed using an ELISA. The V3-V4 region of the 16S rRNA gene was amplified using bacterial DNA from the stool, and about 50 000 high-quality amplicons per sample were grouped into operational taxonomic units for bacteriological analyses. RESULTS: The Bacteroidetes:Firmicutes (B:F) ratio was significantly greater at S3 than S1 (P<0.01). This increase in the B:F ratio between S3 and S1 was found in 15 out of 20 patients. A significant decrease in the concentration of active ghrelin (P=0.003) in the plasma was observed between S3 and S1. There was a statistically significant correlation between the rate of patients whose B:F ratio increased and that of patients whose active ghrelin level decreased between S3 and S1 according to Fisher's exact probability test (P=0.03). CONCLUSIONS: Changes in the gut microbiota, such as the B:F ratio after treatment with antimicrobials, might cause a change in the plasma ghrelin level, as the direct and earliest target of antimicrobials would be the microbiota rather than the hormone-secreting system.

The Ameliorating Effect of Lactobacillus gasseri OLL2716 on Functional Dyspepsia in Helicobacter pylori-Uninfected Individuals: A Randomized Controlled Study.

BACKGROUND/AIMS: Probiotics appear to improve Helicobacter pylori-associated dyspepsia via an inhibitory effect on H. pylori; however, uncertainty exists regarding their effects in H. pylori-uninfected individuals. We evaluated the efficacy of Lactobacillus gasseri OLL2716 (L. gasseri OLL2716) on H. pylori-uninfected individuals with functional dyspepsia (FD). METHODS: A double-blind, parallel-group, placebo-controlled, randomized, controlled trial was performed. Participants were randomly assigned to ingest L. gasseri OLL2716-containing yogurt (L. gasseri OLL2716 group) or L. gasseri OLL2716-free yogurt (placebo group) for 12 weeks. Participants completed questionnaires that dealt with a global assessment as well as symptom severity. The per-protocol (PP) population was evaluated for efficacy in accordance with a plan prepared beforehand. RESULTS: Randomization was performed on 116 individuals; the PP population consisted of 106 individuals (mean age 42.8 ± 9.0). The impressions regarding the overall effect on gastric symptoms were more positive in the L. gasseri OLL2716 group compared to that in the placebo group (statistical trend; p = 0.073). The elimination rate for major FD symptoms was 17.3 and 35.3% in the placebo and L. gasseri OLL2716 groups respectively (p = 0.048). CONCLUSION: L. gasseri OLL2716 has beneficial effects on FD without H. pylori involvement.

Alteration in the gastric microbiota and its restoration by probiotics in patients with functional dyspepsia.

OBJECTIVE: The objective of this study was to comparatively analyse the gastric fluid (GF) microbiota between patients with functional dyspepsia (FD) and healthy controls (HC), and to assess the effect of probiotics on the microbiota. DESIGN: Twenty-four Japanese patients with FD who met the Rome III definition and 21 age-matched and gender-matched HC volunteers were enrolled. The patients with FD had been treated with LG21, a probiotic strain. The GF was sampled after an overnight fast using a nasogastric tube. The bile acids concentration was determined by ELISA. The V3-V4 region of 16S rRNA gene was amplified using bacterial DNA from the GF, and then about 30 000 high-quality amplicons per sample were grouped into operational taxonomic units for analyses. RESULTS: The ratio of GF samples in which the bile acids were detectable was significantly greater in the FD than in the HC groups. In the bacterial composition analysis at the phylum level, the GF microbiota had a Bacteroidetes > Proteobacteria abundance and an absence of Acidobacteria in the FD group, in contrast, the GF microbiota had a Bacteroidetes < Proteobacteria abundance and the presence of Acidobacteria in the HC group. Probiotic therapy in patients with FD shifted the composition of the GF microbiota to that observed in the HC volunteers. CONCLUSIONS: Alteration in the GF microbiota was found in patients with FD compared with HC volunteers. Reflux of the small intestinal contents, including bile acid and intestinal bacteria, to the stomach was suggested to induce a bacterial composition change and be involved in the pathophysiology underlying FD. Probiotics appear effective in the treatment of FD through the normalisation of gastric microbiota. TRIAL REGISTRATION NUMBER: UMINCTR 000022026; Results.

Regulation of gut luminal serotonin by commensal microbiota in mice.

Gut lumen serotonin (5-hydroxytryptamine: 5-HT) contributes to several gastrointestinal functions such as peristaltic reflexes. 5-HT is released from enterochromaffin (EC) cells in response to a number of stimuli, including signals from the gut microbiota. However, the specific mechanism by which the gut microbiota regulates 5-HT levels in the gut lumen has not yet been clarified. Our previous work with gnotobiotic mice showed that free catecholamines can be produced by the deconjugation of conjugated catecholamines; hence, we speculated that deconjugation by bacterial enzymes may be one of the mechanisms whereby gut microbes can produce free 5-HT in the gut lumen. In this study, we tested this hypothesis using germ-free (GF) mice and gnotobiotic mice recolonized with specific pathogen-free (SPF) fecal flora (EX-GF). The 5-HT levels in the lumens of the cecum and colon were significantly lower in the GF mice than in the EX-GF mice. Moreover, these levels were rapidly increased, within only 3 days after exposure to SPF microbiota. The majority of 5-HT was in an unconjugated, free form in the EX-GF mice, whereas approximately 50% of the 5-HT was found in the conjugated form in the GF mice. These results further support the current view that the gut microbiota plays a crucial role in promoting the production of biologically active, free 5-HT. The deconjugation of glucuronide-conjugated 5-HT by bacterial enzymes is likely one of the mechanisms contributing to free 5-HT production in the gut lumen.

Lactobacillus paracasei strain 06TCa19 suppresses inflammatory chemokine induced by Helicobacter pylori in human gastric epithelial cells.

Helicobacter (H.) pylori infection is an important risk factor for gastric cancer that causes gastric inflammation. Inflammatory chemokines such as interleukin (IL)-8 and regulated on activation normal T cell expressed and secreted (RANTES) are elevated in the gastric mucosa by H. pylori. This study aimed to investigate the effects of Lactobacillus paracasei strain 06TCa19, a probiotic strain, on IL-8 and RANTES expression and production induced by H. pylori using human gastric epithelial cell lines. Strain 06TCa19 was shown to suppress H. pylori-mediated elevation of gene expression related to these chemokines in MKN45 cells. The strain also suppressed the increase in IL-8 and RANTES products induced by H. pylori in AGS cells as well as in MKN45 cells. In MKN45 cells inoculated with H. pylori, strain 06TCa19 was shown to downregulate the activation of NF-κB and p38 MAPK signaling pathways. Additionally, the level of the CagA virulence protein of H. pylori in the MKN45 cells and the number of viable H. pylori adhering to MKN45 cells decreased with the addition of strain 06TCa19. Moreover, the strain 06TCa19 notably increased lactic acid in the supernatant of MKN45 cells. Thus, lactic acid released from strain 06TCa19 might have inhibited the adhesion of H. pylori to MKN45 cells and prevented the insertion of H. pylori CagA into the cells, and elevation of IL-8 and RANTES genes and proteins might be suppressed by downregulating the NF-κB and p38 MAPK pathways. Therefore, use of strain 06TCa19 may prevent H. pylori-associated gastric inflammation.

Gut microbiota of mice putatively modifies amino acid metabolism in the host brain.

Recently, it has been found that the gut microbiota influences functions of the host brain by affecting monoamine metabolism. The present study focused on the relationship between the gut microbiota and the brain amino acids. Specific pathogen-free (SPF) and germ-free (GF) mice were used as experimental models. Plasma and brain regions were sampled from mice at 7 and 16 weeks of age, and analysed for free d- and l-amino acids, which are believed to affect many physiological functions. At 7 weeks of age, plasma concentrations of d-aspartic acid (d-Asp), l-alanine (l-Ala), l-glutamine (l-Gln) and taurine were higher in SPF mice than in GF mice, but no differences were found at 16 weeks of age. Similar patterns were observed for the concentrations of l-Asp in striatum, cerebral cortex and hippocampus, and l-arginine (l-Arg), l-Ala and l-valine (l-Val) in striatum. In addition, the concentrations of l-Asp, d-Ala, l-histidine, l-isoleucine (l-Ile), l-leucine (l-Leu), l-phenylalanine and l-Val were significantly higher in plasma of SPF mice when compared with those of GF mice. The concentrations of l-Arg, l-Gln, l-Ile and l-Leu were significantly higher in SPF than in GF mice, but those of d-Asp, d-serine and l-serine were higher in some brain regions of GF mice than in those of SPF mice. In conclusion, the concentration of amino acids in the host brain seems to be dependent on presence of the gut microbiota. Amino acid metabolism in the host brain may be modified by manipulating microbiota communities.

A proliferative probiotic Bifidobacterium strain in the gut ameliorates progression of metabolic disorders via microbiota modulation and acetate elevation.

The gut microbiota is an important contributor to the worldwide prevalence of metabolic syndrome (MS), which includes obesity and diabetes. The anti-MS effects exerted by Bifidobacterium animalis ssp. lactis GCL2505 (BlaG), a highly proliferative Bifidobacterium strain in the gut, and B. longum ssp. longum JCM1217T (BloJ) were comparatively examined. BlaG treatment reduced visceral fat accumulation and improved glucose tolerance, whereas BloJ had no effect on these parameters. Gut microbial analysis revealed that BlaG exerted stronger effects on the overall bacterial structure of the gut microbiota than BloJ, including enrichment of the genus Bifidobacterium. The levels of acetate and glucagon-like peptide-1 were increased by BlaG treatment in both the gut and plasma, but not by BloJ treatment. Correlation analysis suggested that the elevation of gut acetate levels by BlaG treatment plays a pivotal role in the BlaG-induced anti-MS effects. These findings indicated that BlaG, a highly viable and proliferative probiotic, improves metabolic disorders by modulating gut microbiota, which results in the elevation of SCFAs, especially acetate.

Colonic Absorption of Low-Molecular-Weight Metabolites Influenced by the Intestinal Microbiome: A Pilot Study.

Low-molecular-weight metabolites produced by the intestinal microbiome play a direct role in health and disease. However, little is known about the ability of the colon to absorb these metabolites. It is also unclear whether these metabolites are bioavailable. Here, metabolomics techniques (capillary electrophoresis with time-of-flight mass spectrometry, CE-TOFMS), germ-free (GF) mice, and colonized (Ex-GF) mice were used to identify the colonic luminal metabolites transported to colonic tissue and/or blood. We focused on the differences in each metabolite between GF and Ex-GF mice to determine the identities of metabolites that are transported to the colon and/or blood. CE-TOFMS identified 170, 246, 166, and 193 metabolites in the colonic feces, colonic tissue, portal plasma, and cardiac plasma, respectively. We classified the metabolites according to the following influencing factors: (i) the membrane transport system of the colonocytes, (ii) metabolism during transcellular transport, and (iii) hepatic metabolism based on the similarity in the ratio of each metabolite between GF and Ex-GF mice and found 62 and 22 metabolites that appeared to be absorbed from the colonic lumen to colonocytes and blood, respectively. For example, 11 basic amino acids were transported to the systemic circulation from the colonic lumen. Furthermore, many low-molecular-weight metabolites influenced by the intestinal microbiome are bioavailable. The present study is the first to report the transportation of metabolites from the colonic lumen to colonocytes and somatic blood in vivo, and the present findings are critical for clarifying host-intestinal bacterial interactions.

Losartan attenuates the coronary perivasculitis through its local and systemic anti-inflammatory properties in a murine model of Kawasaki disease.

BACKGROUND: Kawasaki disease is a common systemic vasculitis that leads to coronary artery lesions. Besides its antihypertensive effects, losartan can modulate inflammation in cardiovascular disease. We examined whether losartan can attenuate coronary inflammation in a murine model of Kawasaki disease. METHODS AND RESULTS: Five-wk-old C57/BL6J male mice were intraperitoneally injected with Lactobacillus casei cell wall extract to induce coronary inflammation and divided into four groups: placebo, intravenous immunoglobulin (IVIG), losartan, and IVIG+losartan. After 2 wk, mice were harvested. The coronary perivasculitis was significantly attenuated by losartan but not by IVIG alone, and further dramatic attenuation by IVIG+losartan was observed. The frequency of Lactobacillus casei cell wall extract-induced myocarditis (80%) was markedly lowered by losartan (22%) and IVIG+losartan (0%). Furthermore, interleukin (IL)-6 mRNA was markedly attenuated by IVIG+losartan. Serum levels of IL-6, TNF-α, MCP-1, and IL-10 after Lactobacillus casei cell wall extract injection were slightly decreased by IVIG or losartan. Moreover, IL-1ß, IL-10, and MCP-1 levels were significantly decreased by IVIG+losartan. CONCLUSION: The addition of losartan to IVIG strongly attenuated the severity of coronary perivasculitis and the incidence of myocarditis, along with suppressing systemic/local cytokines as well as the activated macrophage infiltration. Therefore, losartan may be a potentially useful additive drug for the acute phase of Kawasaki disease to minimize coronary artery lesions.

Gastric microbiota in the functional dyspepsia patients treated with probiotic yogurt.

OBJECTIVE: To investigate the structure of the gastric microbiota in functional dyspepsia (FD) and its role in the pathophysiology. DESIGN: We compared the basic physiological properties of the gastric fluid (GF) and the structure of the microbiota in the GF of 44 healthy control (HC) participants and 44 patients with FD. We then treated the patients with FD with a yogurt containing a probiotic strain of Lactobacillus gasseri OLL2716 (LG21 yogurt) and investigated the effects on the bacteriological parameters and symptoms to examine the relationship between them. RESULTS: The volume of GF recovered from the stomach after overnight fasting was greater in the patients with FD than in the HCs, and decreased in the patients with FD whose symptoms were improved by the LG21 yogurt treatment. An analysis using a terminal restriction fragment polymorphism method demonstrated that the overall structure of the bacterial community and the abundance of genus Prevotella in the GF of the patients in the FD group were significantly different from those in the HC group. In the patients with FD, this bacteriological change was restored by treatment with LG21 yogurt. A significant inverse correlation was found between the abundance of Prevotella and the severity of postprandial distress-like symptoms in patients with FD who received LG21 yogurt. CONCLUSIONS: Significant dysbiosis was found in the GF microbiota of patients with FD and considered to be involved in the pathogenesis. The abundance of genus Prevotella in the GF may be used as a biomarker of the efficacy of the treatment of FD. TRIAL REGISTRATION NUMBER: UMINCTR000022026.

Effects of Lactobacillus gasseri OLL2716 on Helicobacter pylori-Associated Dyspepsia: A Multicenter Randomized Double-Blind Controlled Trial.

Some Lactobacillus spp. suppress Helicobacter pylori in the stomach and have potential therapeutic applications for the treatment of gastrointestinal conditions. In this study, the effects of Lactobacillus strains on functional dyspepsia associated with H. pylori infection were examined. Volunteers were screened using the (13)C-urea breath test (UBT) and H. pylori stool test, and 131 participants who met the selection criteria (mean age: 48.9 years) were randomly given L. gasseri OLL2716-containing yogurt or placebo yogurt once daily for 12 weeks. Gastrointestinal symptoms (epigastric pain, bloating, postprandial fullness, nausea, and heartburn) and the levels of serum pepsinogen (PG), (13)C-UBT, and H. pylori stool antigen were assessed. No significant differences were observed between the groups in UBT results, H. pylori stool antigens, or the serum PGI/II ratio. In the L. gasseri group, postprandial fullness was significantly lower at the end of the trial compared to the initial level (p < 0.05) and significantly fewer patients had a VAS score of >10 for bloating compared to the placebo group (p < 0.05). Dietary supplementation with L. gasseri OLL2716-containing yogurt may effectively suppress dyspeptic symptoms in H. pylori-infected patients. This study was registered at the University Hospital Medical Network Clinical Trial Registry (UMIN000016746).