Mouse Adaptation of Human Inflammatory Bowel Diseases Microbiota Enhances Colonization Efficiency and Alters Microbiome Aggressiveness Depending on Recipient Colonic Inflammatory Environment.

Understanding the cause vs consequence relationship of gut inflammation and microbial dysbiosis in inflammatory bowel diseases (IBD) requires a reproducible mouse model of human-microbiota-driven experimental colitis. Our study demonstrated that human fecal microbiota transplant (FMT) transfer efficiency is an underappreciated source of experimental variability in human microbiota associated (HMA) mice. Pooled human IBD patient fecal microbiota engrafted germ-free (GF) mice with low amplicon sequence variant (ASV)-level transfer efficiency, resulting in high recipient-to-recipient variation of microbiota composition and colitis severity in HMA Il-10-/- mice. In contrast, mouse-to-mouse transfer of mouse-adapted human IBD patient microbiota transferred with high efficiency and low compositional variability resulting in highly consistent and reproducible colitis phenotypes in recipient Il-10-/- mice. Human-to-mouse FMT caused a population bottleneck with reassembly of microbiota composition that was host inflammatory environment specific. Mouse-adaptation in the inflamed Il-10-/- host reassembled a more aggressive microbiota that induced more severe colitis in serial transplant to Il-10-/- mice than the distinct microbiota reassembled in non-inflamed WT hosts. Our findings support a model of IBD pathogenesis in which host inflammation promotes aggressive resident bacteria, which further drives a feed-forward process of dysbiosis exacerbated gut inflammation. This model implies that effective management of IBD requires treating both the dysregulated host immune response and aggressive inflammation-driven microbiota. We propose that our mouse-adapted human microbiota model is an optimized, reproducible, and rigorous system to study human microbiome-driven disease phenotypes, which may be generalized to mouse models of other human microbiota-modulated diseases, including metabolic syndrome/obesity, diabetes, autoimmune diseases, and cancer.

Characteristics of Gastric Mucosa-Associated Microbiota in Patients with Early Gastric Cancer After Successful Helicobacter pylori Eradication.

BACKGROUND: Helicobacter pylori (H. pylori) is widely recognized as a definite carcinogen in gastric cancer (GC). Although H. pylori eradication reduces the risk of GC, GC recurrence has been detected even after successful H. pylori eradication. Recently, the analysis of gut microbiota was reported. AIMS: This study aimed to evaluate the correlation between gastric mucosa-associated microbiota (G-MAM) and early gastric cancer (EGC) after successful H. pylori eradication. METHODS: In this pilot study, G-MAM were collected during the esophagogastroduodenoscopy of 17 patients, receiving H. pylori eradication therapy at least 5 years ago. The patients were divided into those with EGC (the EGC group, 8 patients) and those without EGC (the NGC group, 9 patients). Microbial samples in the greater curvature of the pyloric site were obtained using an endoscopic cytology brush, and the G-MAM profiles of each sample were analyzed using 16S rRNA V3-V4 gene sequencing. RESULTS: Between the two groups, there was no significant difference in the median age, sex, median period after successful eradication of H. pylori, the α diversity, and the average abundance at the phylum level. At the genus level, the average abundance of Unclassified Oxalobacteraceae, Capnocytophaga, and Haemophilus was significantly lower in the EGC group than in the NGC group (0.89 vs. 0.14%, P < 0.01, 0.28 vs. 0.00%, P < 0.01 and 5.84 vs. 2.16%, P = 0.034, respectively). CONCLUSIONS: We demonstrated alternations in the profiles of G-MAM between the two groups. Our results suggest that G-MAM may influence carcinogenesis after successful H. pylori eradication.

Clinical Background Factors as Predictors of the Efficacy of 5-Aminosalicylic Acid Suppositories in Patients with Ulcerative Colitis.

Introduction: Although the efficacy of 5-aminosalicylic acid (ASA) suppositories for ulcerative colitis (UC) has been reported in many studies, many studies have also described poor adherence to 5-ASA suppository regimens. We aimed to identify the clinical background factors that influence adherence to 5-ASA suppositories to improve adherence and efficacy of the treatment. Methods: We conducted a retrospective cohort study of 61 patients with active UC who were using 5-ASA suppositories. All patients underwent endoscopy and rectal biopsy for histological diagnosis prior to 5-ASA suppository treatment. The efficacy of 5-ASA suppository treatment was compared in relation to clinical background factors (sex, age, disease duration, disease type, clinical activity, Ulcerative Colitis Endoscopic Index of Severity, histological activity, serum C-reactive protein level, concomitant use of immunomodulators, history of steroid use, and dose of oral 5-ASA). Results: The efficacy of 5-ASA suppositories was significantly related to low Lichtiger Colitis Activity Index (LCAI) scores and proctitis type prior to its use. In terms of sex, females tended to show higher efficacy. Multivariate logistic regression analysis using these three factors showed high predictive value for the efficacy of 5-ASA suppositories (AUC, 0.788; sensitivity, 87.2%; and specificity, 63.7%). Conclusion: This study is the first to extract clinical background factors for predicting the efficacy of 5-ASA suppositories. The use of 5-ASA suppositories in patients who are expected to show efficacy will be effective in improving patient co-operation.

Mucosal Addressin Cell Adhesion Molecule 1 Expression Reflects Mucosal Inflammation and Subsequent Relapse in Patients with Ulcerative Colitis.

BACKGROUND AND AIMS: Mucosal addressin cell adhesion molecule 1 [MAdCAM-1] is upregulated in the vascular endothelium of the colonic mucosa in ulcerative colitis [UC]. Although the association between MAdCAM-1 expression and mucosal inflammation has been discussed, the association with the clinical course of UC patients has not been reported. In this study we investigated not only the association between mucosal MAdCAM-1 expression and mucosal inflammation, but also its association with subsequent relapse in UC patients with clinical remission. METHODS: Eighty UC patients in remission who visited Kyoto Prefectural University of Medicine for follow-up for 2 years were included. Biopsy samples were collected during colonoscopy, and transcriptional expression levels of UC-related cytokines and MAdCAM-1 were quantified using real-time polymerase chain reaction. MAdCAM-1 mRNA expression and protein expression by immunohistochemistry were compared in patients who subsequently relapsed and those who remained in remission and were examined in relation to endoscopic findings, histological activity and cytokine expression. RESULTS: MAdCAM-1 expression was correlated with endoscopic severity, and significantly elevated in histologically active mucosa than inactive mucosa. Furthermore, MAdCAM-1 expression levels were closely correlated with those of several cytokines. MAdCAM-1 mRNA and protein expression were significantly higher in the relapse group than in the remission group, indicating that MAdCAM-1 expression in the mucosa is already elevated in UC patients in clinical remission who subsequently relapse. CONCLUSIONS: MAdCAM-1 expression in the colonic mucosa of UC patients is related to mucosal inflammation and subsequent relapse; it may serve as a marker for both relapse and therapeutic effectiveness in UC.

Effects of Smoking on the Gut Microbiota in Individuals with Type 2 Diabetes Mellitus.

Smoking affects eating habits; however, few studies on smoking and the gut microbiota have reported the effects of diet in detail. This cross-sectional study aimed to determine the association between smoking and the gut microbiota, considering the impact of smoking on dietary intake. Dietary habits and the composition of the gut microbiota were assessed in 195 men with type 2 diabetes (164 non-current smokers and 31 current smokers) using a brief self-administered diet history questionnaire and 16S ribosomal RNA gene sequencing of fecal samples. The data were compared according to the current smoking status of the participants. Current smokers had high alcohol and sugar/sweetener intake and low fruit intake. The proportion of the Coprococcus genus was higher among current smokers. Multiple regression analysis adjusted for current smoking, age, exercise habits, alcohol intake, sugar and sweetener intake, and fruit intake showed that smoking was associated with the proportion of the Coprococcus genus. Current smoking was associated with both dietary intake and composition of the gut microbiota. Although dietary intake should be considered when investigating the association between smoking and the gut microbiota, the results suggest that the direct effect of smoking is more significant.

Retrospective investigation of mesalamine intolerance in patients with ulcerative colitis.

Mesalamine is a key drug in the treatment of ulcerative colitis (UC) for both induction and maintenance therapy. On the other hand, it is known that there are some cases of mesalamine intolerance that are difficult to distinguish from symptoms due to aggravation of UC. The aim of this study is to investigate the clinical characteristic of mesalamine intolerance in UC. A retrospective, observational study was conducted. We enrolled 31 patients who were diagnosed as mesalamine intolerance between April 2015 to March 2020. We examined clinical features, time to onset, drug types of mesalamine, DLST positive rate, colonoscopy findings, disease activity, and clinical course after diagnosis. The average dose of mesalamine was 3.69 g and DLST-positive was 57.1%. Within the first 2 weeks from the start of mesalamine, 51.6% showed symptoms of intolerance. The serum CRP level was relatively high at ≥10.0 mg/dl in 53.6% of the cases. There was no difference in clinical background, symptoms, or laboratory findings between patients with DLST-positive and negative. In this study, we clarified the clinical characteristics of mesalamine intolerant patients, and found no difference in the clinical background or success rate of desensitization therapy between positive and negative DLST cases.

Investigation on the Inhibitory Effect of Wnt-5a on Colonic Mucosal Inflammation in Patients with Ulcerative Colitis.

BACKGROUND: Recent progress in ulcerative colitis (UC) treatment has been remarkable, and various medications have been applied. However, some patients with UC are refractory to treatment and convert to surgery. AIM: To investigate the role of colonic mucosal Wnt-5a expression in the pathogenesis of UC and the effect of bioactive Wnt-5a peptide on colitis in mice. METHODS: Wnt-5a peptide was intraperitoneally administered to mice every day from the beginning of dextran sulfate sodium (DSS) treatment. The severity of colitis was evaluated based on body weight change, colonic length, and histological scores. Colonic mucosal TNF-α and KC mRNA expression levels were measured. This study included 70 patients with UC in clinical remission. Wnt-5a, TNFα, and IL-8 mRNA expression in the rectal mucosa were measured by quantitative real-time polymerase chain reaction using biopsy materials. Wnt-5a mRNA expression levels were compared between patients who relapsed and those in remission. We examined the correlation of Wnt-5a expression with TNF-α and IL-8 expression. RESULTS: Wnt-5a peptide significantly attenuated the severity of DSS-induced colitis. Moreover, mucosal TNF-α and KC mRNA expression were significantly suppressed by Wnt-5a peptide treatment. Wnt-5a mRNA levels were significantly lower in patients with subsequent relapse than in those who remained in remission. Mucosal Wnt-5a was inversely correlated with TNF α and IL-8 expression. CONCLUSION: Wnt-5a peptide suppressed colitis in mice, and decreased Wnt-5a expression was strongly associated with relapse in patients with UC. Wnt-5a may have an inhibitory effect on mucosal inflammation in UC, and Wnt-5a peptide could be a new therapeutic strategy.

Mucosal interleukin-8 expression as a predictor of subsequent relapse in ulcerative colitis patients with Mayo endoscopic subscore 0.

BACKGROUND AND AIM: Complete endoscopic mucosal healing is defined as a Mayo endoscopic subscore of 0. Some patients diagnosed with a Mayo endoscopic subscore 0 may present with subsequent clinical relapse. Here, we aimed to demonstrate mucosal cytokine profile as a predictor of clinical relapse in ulcerative colitis patients with a Mayo endoscopic subscore of 0 as a marker of mucosal healing. METHODS: We conducted prospective observational pilot study to examine the relationship between mucosal cytokine expression and subsequent relapse of UC patients diagnosed with a Mayo endoscopic subscore of 0. We enrolled 55 patients, and expression of cytokines tumor necrosis factor-α, interferon γ, interleukin-1ß, interleukin-2, interleukin-4, interleukin-5, interleukin-6, interleukin-7, interleukin-8, interleukin-9, interleukin-10, interleukin-12, interleukin-13, interleukin-15, interleukin-17A, interleukin-17F, interleukin-18, interleukin-21, interleukin-22, interleukin-23, interleukin-27, and interleukin-33 was measured by quantitative real-time PCR using rectal mucosa biopsy materials. Cytokine expression levels were compared between patients who relapsed between March 1, 2016, and March 30, 2020, of the study period and those who remained in remission. RESULTS: Ten cytokines, including interleukin-2, interleukin-4, interleukin-8, interleukin-10, interleukin-12, interleukin-15, interleukin-17A, interleukin-21, interleukin-23, and interleukin-33, were significantly elevated in patients with subsequent relapse compared with those who remained in remission. Interleukin-8 expression was the most useful predictor. CONCLUSIONS: In the rectal mucosa of ulcerative colitis patients with Mayo endoscopic subscore 0, levels of several cytokines were elevated in cases of subsequent relapse. Among these, interleukin-8 expression was the most useful for predicting relapse.

Unique Habitual Food Intakes in the Gut Microbiota Cluster Associated with Type 2 Diabetes Mellitus.

This cross-sectional study aimed to clarify the characteristic gut microbiota of Japanese patients with type 2 diabetes (T2DM) using t-distributed stochastic neighbor embedding analysis and the k-means method and to clarify the relationship with background data, including dietary habits. The gut microbiota data of 383 patients with T2DM and 114 individuals without T2DM were classified into red, blue, green, and yellow groups. The proportions of patients with T2DM in the red, blue, green, and yellow groups was 86.8% (112/129), 69.8% (81/116), 76.3% (90/118), and 74.6% (100/134), respectively; the red group had the highest prevalence of T2DM. There were no intergroup differences in sex, age, or body mass index. The red group had higher percentages of the Bifidobacterium and Lactobacillus genera and lower percentages of the Blautia and Phascolarctobacterium genera. Higher proportions of patients with T2DM in the red group used α-glucosidase inhibitors and glinide medications and had a low intake of fermented soybean foods, including miso soup, than those in the other groups. The gut microbiota pattern of the red group may indicate characteristic changes in the gut microbiota associated with T2DM in Japan. These results also suggest that certain diabetes drugs and fermented foods may be involved in this change. Further studies are needed to confirm the relationships among traditional dietary habits, the gut microbiota, and T2DM in Japan.

The efficacy of linked color imaging for the endoscopic diagnosis of mucosal healing in quiescent ulcerative colitis.

BACKGROUND AND AIM: The Mayo Endoscopic Subscore (MES) and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) are used to assess endoscopic mucosal healing in patients suffering from ulcerative colitis. Although mucosal healing is defined by MES 0, relapse of ulcerative colitis is often observed. Over a 48-month period, this study investigated the efficacy of linked color imaging (LCI) in predicting the long-term prognosis of ulcerative colitis patients diagnosed with MES 0. METHODS: Overall, 26 patients in ulcerative colitis remission, diagnosed with MES 0, were enrolled. Using a LASEREO endoscopic system (Fujifilm Co., Tokyo, Japan), endoscopic colonic images were assessed with linked color imaging and the colitis endoscopic index of severity. Endoscopic LCI images were separated into three subgroups (A, no redness; B, redness with visible vessels; and C, redness without visible vessels). The Geboes score was used to evaluate histology; active mucosa was defined as GS > 2B.1. RESULTS: Linked color imaging classification subdivided colonic mucosa, which had been diagnosed with MES 0, into two classes. The LCI-A group did not relapse, and the non-relapse rate was significantly higher (P = 0.018) than that in the LCI-B group. No difference in relapse rates was observed between patients with a colitis endoscopic index of severity of 0 and 1 (P = 0.655). There was no statistical difference between the composition of LCI-A group and the relapse rate between active and inactive mucosa diagnosed by Geboes score. CONCLUSIONS: This methodology can be used to evaluate mucosal healing and predict long-term outcomes in ulcerative colitis patients.

Low serum albumin at admission is a predictor of early colectomy in patients with moderate to severe ulcerative colitis.

BACKGROUND AND AIM: Several studies have identified postinduction therapy predictors of long-term outcomes of ulcerative colitis (UC) in patients who experienced the first attack of the disease or relapsed after therapy. We aimed to identify the preinduction therapy predictors at admission that predicted early colectomy in patients with moderate to severe UC. METHODS: Ninety-five patients with moderate to severe UC who underwent induction therapy at the Kyoto Prefectural University of Medicine hospital between August 2008 and March 2020 were retrospectively included and categorized into two groups: the colectomy group (n = 27) and the noncolectomy group (n = 68). The clinical parameters (age, gender, disease extent, and disease activity on admission), induction therapies administered [including 5-aminosalicylic acid, steroids, immunomodulators, calcineurin inhibitor, and anti-Tumor Necrosis Factor (TNF)-α antibodies], and laboratory data (hemoglobin, albumin, C-reactive protein, and cytomegalovirus reactivation on admission) were evaluated and compared between the two groups. Multivariate logistic regression analyses were performed to identify significant predictors of early colectomy, and P < 0.05 was considered significant. RESULTS: All clinical parameters were not significant predictors of colectomy. Among laboratory parameters, the serum albumin level on admission was a significant independent predictor of colectomy (odds ratio: 6.097, 95% confidence interval: 1.8310-20.3047). Receiver operating characteristic curves were plotted for the serum albumin levels of the 95 patients at admission. The cut-off value of serum albumin was 2.45 g/dL. CONCLUSIONS: When the serum albumin level of UC patients at admission is below 2.45 g/dL, we should consider presenting the option of surgical treatment to patients.

Increased mucosal IL-12 expression is associated with relapse of ulcerative colitis.

BACKGROUND: The role of IL-12/23 in the pathogenesis of ulcerative colitis (UC) is unclear. We analyzed mucosal IL-12/23 expression and its relationship with endoscopic severity, histological activity, and UC relapse. METHODS: Rectal biopsies were collected from 70 UC patients with clinical remission. IL-12, IL-23, IFN-γ, IL-17A, and IL-17F mRNA expression was measured by real-time PCR. Endoscopic severity and histological activity were evaluated using the Mayo endoscopic subscore (MES) and the Geboes score, respectively. RESULTS: The longest follow-up period was 51 months. Thirty-four patients relapsed during the study period. Samples from these subsequently relapsed patients formed the "relapse" group, while those from patients that did not relapse formed the "remission" group. IL-12 (P = 0.0003) and IL-23 (P = 0.014) mRNA expression was significantly higher in the relapse than the remission group. Expression of IL-23 (P = 0.015) but not IL-12 (P = 0.374) was correlated with MES. However, in patients with an MES of 0 and 1, IL-12 expression was statistically higher in the relapse than the remission group (P = 0.0015, P = 0.0342). IL-12 and IL-23 expression did not vary significantly between histologically active and inactive mucosa; both were higher in histologically inactive patients in the remission group (IL-12: P = 0.0002, IL-23: P = 0.046). CONCLUSIONS: Rectal IL-12 and IL-23 expression was elevated in the relapse group, but IL-12 was more strongly associated with UC relapse, irrespective of endoscopic severity and histological activity. Mucosal IL-12 was elevated in patients with deep mucosal healing. Our results suggest an important role of IL-12 in UC pathogenesis and the molecular mechanism of UC relapse.

[A Case of Initially Unresectable Advanced Gastric Cancer Radically Resected by Conversion Surgery after Nivolumab Immunotherapy].

A 77-year-old man was admitted to our hospital with symptoms of epigastralgia and vomiting. Detailed investigation revealed unresectable advanced gastric cancer accompanied by multiple lymph node metastases and invasion of the pancreas(UM, type 3, cT4b, N3, M0, Stage ⅢC). The patient received nivolumab immunotherapy after first-line S-1 plus oxaliplatin(SOX)chemotherapy and second-line nab-paclitaxel(PTX)plus ramucirumab(RAM)chemotherapy. Remarkable tumor reduction was observed after 3 courses of nivolumab immunotherapy, and the patient subsequently underwent radical total gastrectomy with splenectomy and D2 lymphadenectomy. Histopathological examination of the resected stomach showed a near complete response, and only small metastatic foci remained in No. 2 lymph nodes, resulting in R0 resection. The patient was followed up without adjuvant therapy, and he is alive 6 months after the treatment without any symptoms of recurrence. The mechanism of action of immune checkpoint inhibitors is fundamentally different from that of conventional cytotoxic chemotherapeutic agents. Recently, several reports have described good responses to immune checkpoint inhibitors in cases where conventional chemotherapy has been unsuccessful. When predictive biomarkers of response to immune checkpoint inhibitors are identified, a combination therapy of preceding immunotherapy and subsequent surgery might provide an efficient radical therapeutic effect even in cases of unresectable advanced gastric cancer.

Changes in the Gut Microbiota are Associated with Hypertension, Hyperlipidemia, and Type 2 Diabetes Mellitus in Japanese Subjects.

The human gut microbiota is involved in host health and disease development. Therefore, lifestyle-related diseases such as hypertension (HT), hyperlipidemia (HL), and type 2 diabetes mellitus (T2D) may alter the composition of gut microbiota. Here, we investigated gut microbiota changes related to these diseases and their coexistence. This study involved 239 Japanese subjects, including healthy controls (HC). The fecal microbiota was analyzed through the isolation of bacterial genomic DNA obtained from fecal samples. Although there were no significant differences in the microbial structure between groups, there was a significant difference in the α-diversity between HC and the patients in whom two diseases coexisted. Moreover, Actinobacteria levels were significantly increased, whereas Bacteroidetes levels were significantly decreased in all disease groups. At the genus level, Bifidobacterium levels were significantly increased in the HL and T2D groups, as were those of Collinsella in all disease groups. In contrast, Alistipes levels were significantly lower in the HL group. Furthermore, metabolic enzyme families were significantly increased in all disease groups. Interestingly, the structure and function of the gut microbiota showed similar profiles in all the studied diseases. In conclusion, several changes in the structure of the gut microbiota are associated with T2D, HT, and HL in Japanese subjects.

Fatal gastrointestinal bleeding due to IgA vasculitis complicated with tuberculous lymphadenitis: A case report and literature review.

We report a case of IgA vasculitis that developed during the treatment of tuberculosis. Patients with tuberculosis who are on antituberculosis treatment can be administered steroids for severe disease or complications.

Intake of sucrose affects gut dysbiosis in patients with type 2 diabetes.

AIMS/INTRODUCTION: Gut dysbiosis is generally associated with type 2 diabetes mellitus. However, the effect of habitual dietary intake on gut dysbiosis in Japanese patients with type 2 diabetes mellitus has not yet been explicated. This study investigated whether alteration of the gut microbiota was influenced by dietary intake of sucrose in Japanese patients with type 2 diabetes mellitus. MATERIALS AND METHODS: In this cross-sectional study, 97 patients with type 2 diabetes mellitus and 97 healthy individuals were matched by age and sex, and then, fecal samples were obtained. Next-generation sequencing of the 16S ribosomal ribonucleic acid gene was carried out, and functional profiles for the gut microbiota were analyzed. We selected the top 30 gut microbial genera and top 20 functional profiles for the gut microbiota specified by the weighted average difference method. The association between gut microbial genera or functional profiles and habitual dietary intake was investigated by Spearman's rank correlation coefficient, and then, clustering analysis was carried out to clarify the impact of habitual dietary intake. RESULTS: The Actinobacteria phylum was highly abundant in patients with type 2 diabetes mellitus, whereas the Bacteroidetes phylum was less abundant. Diabetic-type gut microbes, specifically Bacteroides and Bifidobacterium, were altered by sucrose intake at the genus level. Furthermore, sucrose intake was associated with glycolysis/gluconeogenesis in the diabetic-type functional profiles of the gut microbiota. CONCLUSIONS: The gut microbiota and functional profiles for the gut microbiota in patients with type 2 diabetes mellitus were significantly different from those in healthy individuals. Furthermore, we showed that sucrose intake was closely associated with these differences.

Promotion of wound healing by acetate in murine colonic epithelial cell via c-Jun N-terminal kinase activation.

BACKGROUND AND AIM: Mucosal healing is an important clinical goal in patients with inflammatory bowel disease. Recently, short-chain fatty acids (SCFAs) have been reported to have multifaceted effects to host. However, the effects of SCFAs on wound healing in intestinal epithelial cells are unclear. In the present study, we investigated the effects of acetate, one of the major SCFAs, on the wound healing of murine colonic epithelial cells. METHODS: Young adult mouse colonic epithelial cells were used to determine the effect of acetate using wound healing assay. Mitogen-activated protein kinase and Rho kinase inhibitor were used to elucidate intracellular signal of wound healing treated with acetate. Meanwhile, Rho activation assays were utilized to measure Rho activation levels. To assess in vivo effects, C57B6 mice with dextran sodium sulfate for 7 days were treated with enema administration of acetate for 7 days. Body weight, disease activity index, colon length, and mucosal break ratio in histology were examined. RESULTS: Acetate enhanced wound healing and fluorescence intensity of actin stress fiber compared with control. These effects were canceled with pretreatment of c-Jun N-terminal kinase (JNK) inhibitor or Rho kinase inhibitor. Furthermore, JNK inhibitor reduced the activation of Rho induced by acetate. In the dextran sodium sulfate-induced colitis model, the mice with enema treatment of acetate significantly exhibited recovery. CONCLUSIONS: In this study, we demonstrated that acetate promoted murine colonic epithelial cell wound healing via activation of JNK and Rho signaling pathways. These findings suggested that acetate could have applications as a therapeutic agent for patients with intestinal mucosal damage, such as inflammatory bowel disease.

Mucosa-Associated Microbiota in the Gastrointestinal Tract of Healthy Japanese Subjects.

BACKGROUND: The importance of microbiota infiltrating the gut mucus layer has been reported in the pathogenesis of various gastrointestinal and systemic diseases. However, little is known about the mucosa-associated microbiota (MAM) in healthy subjects. The present study aimed to clarify the characteristics of the gastrointestinal MAM from the oral cavity to the rectum in healthy Japanese subjects. METHODS: Seventeen healthy subjects were enrolled. In this study, 5 mucosa samples from the upper gut (intraoral, mid-esophagus, gastric corpus, gastric antrum, and duodenum) and 7 from the lower gut (ileum, cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum) were collected with a brush under endoscopic examination. MAM profiles of each sample were analyzed by 16S-rRNA V3-V4 gene sequences. RESULTS: Collecting mucosa samples by brushing provided sufficient material for MAM profiling without causing adverse effects. The upper and lower gut MAM profiles differed significantly (p < 0.0001). In the upper and lower gut, the intra- and inter-individual MAM profiles were significantly different (p = 0.0008 and p < 0.0001 respectively). CONCLUSIONS: The MAM profiles of the upper and lower gut were significantly different. The inter-individual differences in MAM were remarkable compared to the intra-individual differences.

Higher Levels of Streptococcus in Upper Gastrointestinal Mucosa Associated with Symptoms in Patients with Functional Dyspepsia.

BACKGROUND: Functional dyspepsia (FD) is associated with poor health-related quality of life. Recent evidence suggests that the main pathogenesis suspect is the gut mucosa-associated microbiota (MAM). However, little is known about the MAM in FD subjects. The aim of this study was to clarify the relationship between upper gastrointestinal symptoms in FD and the characteristics of the gastrointestinal MAM. SUMMARY: Five mucosa samples from the upper gut (intraoral, mid-esophagus, gastric body, gastric antrum, and descending portion of the duodenum) were collected with a brush under endoscopic examination from FD and healthy control subjects. MAM profiles of each sample were analyzed by 16S-rRNA -V3-V4 gene sequences. Questionnaire was used to assess gastrointestinal symptoms in FD. Between FD and healthy control subjects, although the comparison of MAM α-diversity showed no significant differences, the structure of MAM (ß-diversity) was clearly different. Only the phylum Firmicutes was increased in FD compared to healthy control subjects in all sites of the upper gut. At the genus level, Streptococcus was significantly increased in all sites in the upper gut in FD. The relative abundance of Streptococcus was positively correlated with upper gastrointestinal symptoms in each upper gut group. Furthermore, the relative abundance of OTU 90 was positively correlated with upper gastrointestinal symptoms in all sites in the upper gut in FD. Key Messages: Streptococcus is a bacterium strongly correlated with upper gastrointestinal symptoms in FD.

Gut microbiota differences in elderly subjects between rural city Kyotango and urban city Kyoto: an age-gender-matched study.

Several outcomes have been reported on the role of gut microbiota in health promotion and disease prevention. Kyotango, one of the longevity areas with various centenarians, is a provincial city located in the northern part of Kyoto Prefecture in Japan. To understand the relationship between gut microbiota and urbanization, we compared the diversity, abundance, and function of gut microbiota in older healthy subjects between Kyotango and Kyoto cities; Kyoto is an urban city located in the southern part of Kyoto Prefecture. In total, 51 subjects at Kyotango and 51 subjects at Kyoto matched by age and gender were recruited, and their fecal samples were obtained to analyze the gut microbiota using 16S rRNA gene sequencing. Principal coordinate analysis for ß-diversity revealed significant differences in the gut microbiota between two cities. In contrast, the analysis of α-diversity revealed no significant differences between the groups. On comparison at the phylum levels, the abundance of Firmicutes was decreased with the urbanization, whereas that of Proteobacteria and Bacteroidetes increased. On comparison at the genus levels, with urbanization, a significant decrease was observed in Lachnospiraceae families including genus Roseburia and Coprococcus, and significant increases was observed in Bacteroides, Oscillospira, Parabacteroides, and Ruminococcus. The most markedly increased functional pathway with urbanization was lipopolysaccharide biosynthesis proteins and lipopolysaccharide biosynthesis, and decreased pathway was transporters and ABC transporters. In conclusion, the present findings indicate significant differences in the gut microbiota between the provincial city and urban cities at Kyoto Prefecture. These alterations in the microbiota may provide new insights to consider the relationship between longevity and gut microbiota.