The interplay between alterations in esophageal microbiota associated with Th17 immune response and impaired LC20 phosphorylation in achalasia.

BACKGROUND: Achalasia is an esophageal motility disorder with an unknown etiology. We aimed to determine the pathogenesis of achalasia by studying alterations in esophageal smooth muscle contraction and the associated inflammatory response, and evaluate the role of esophageal microbiota in achalasia development. METHODS: We analyzed esophageal mucosa and lower esophageal sphincter (LES) samples, obtained from patients with type II achalasia who underwent peroral endoscopic myotomy. Esophageal conditioned media obtained from patients were transferred into the mouse esophagus to determine whether the esophageal intraluminal environment is associated with achalasia. RESULTS: Approximately 30% of 20-kDa myosin light chains (LC20) was phosphorylated in LES from the control group under resting and stimulated conditions, whereas less than 10% of LC20 phosphorylation was detected in achalasia under all conditions. The hypophosphorylation of LC20 in achalasia was associated with the downregulation of the myosin phosphatase-inhibitor protein CPI-17. Th17-related cytokines, including IL-17A, IL-17F, IL-22, and IL-23A, were significantly upregulated in achalasia. α-Diversity index of esophageal microbiota and the proportion of several microbes, including Actinomyces and Dialister, increased in achalasia. Actinomyces levels positively correlated with IL-23A levels, whereas Dialister levels were positively associated with IL-17A, IL-17F, and IL-22 levels. Esophageal IL-17F levels increased in mice after oral administration of the conditioned media. CONCLUSIONS: In LES of patients with achalasia, hypophosphorylation of LC20, a possible cause of impaired contractility, was associated with CPI-17 downregulation and an increased Th17-related immune response. The esophageal intraluminal environment, represented by the esophageal microbiota, could be associated with the development and exacerbation of achalasia.

Lower Dose of 5 mL of 1% Lidocaine is More Suitable than the Conventional 10 mL for Caudal Block in Transrectal Prostate Biopsy: A Retrospective Cohort Study.

Objectives: In Japan, caudal block with 1% lidocaine is commonly used for transrectal prostate biopsy. Although 10 mL of 1% lidocaine is commonly used, the appropriate dosage of 1% lidocaine has not been studied. Our hospital routinely uses two different doses (5 or 10 mL) of 1% lidocaine for caudal block for transrectal prostate biopsy. Herein, we retrospectively evaluated the efficacy and safety of both doses of 1% lidocaine. Methods: This retrospective study included 869 patients who underwent transrectal prostate biopsy with caudal block at our hospital. The amount of 1% lidocaine was determined by the day of the week on which the biopsy was performed, and the patient voluntarily chose the day of the biopsy, unaware of the dose of 1% lidocaine used on that day. Pain, anal sphincter tonus, cancer diagnosis rate, and early complications were compared. Results: In total, 466 and 403 patients received 5 and 10 mL of 1% lidocaine for a caudal block, respectively. After propensity-score matching for patient characteristics, each group contained 395 patients. The pain score, anal sphincter tonus score, or prostate cancer diagnosis rate were not significantly different between the two groups. However, rectal bleeding was significantly more frequent and severe in the 10-mL than the 5-mL group (p=0.018 and p=0.0036, respectively). The incidence of other complications was not significantly different between the groups. Conclusions: Our results suggest that 5 mL of 1% lidocaine may be more suitable than 10 mL for caudal block during transrectal prostate biopsy.

Interception of Epoxide ring to quorum sensing system in Enterococcus faecalis and Staphylococcus aureus.

Quorum sensing inhibitor (QSI) has been attracting attention as anti-virulence agent which disarms pathogens of their virulence rather than killing them. QSI marking cyclic peptide-mediated QS in Gram-positive bacteria is an effective tool to overcome the crisis of antibiotic-dependent chemotherapy due to the emergence of drug resistance strain, e.g., methicillin resistant Staphylococcus aureus (MRSA) and Vancomycin resistant Enterococci (VRE). From a semi-large-scale screening thus far carried out, two Epoxide compounds, Ambuic acid and Synerazol, have been found to efficiently block agr and fsr QS systems, suggesting that the Epoxide group is involved in the mode of action of these QSIs. To address this notion, known natural Epoxide compounds, Cerulenin and Fosfomycin were examined for QSI activity for the agr and fsr systems in addition to in silico and SAR studies. As a result, most of investigated Epoxide containing antibiotics correlatively interfere with QSI activity for the agr and fsr systems under sublethal concentrations.

Cyclic pairwise interaction representing a rock-paper-scissors game maintains the population of the vulnerable yeast Saccharomyces cerevisiae within a multispecies sourdough microbiome.

IMPORTANCE: Traditionally, multispecies consisting of lactic acid bacteria and yeasts collaboratively engage sourdough fermentation, which determines the quality of the resulting baked goods. Nonetheless, the successive transfer of these microbial communities can result in undesirable community dynamics that prevent the formation of high-quality sourdough bread. Thus, a mechanistic understanding of the community dynamics is fundamental to engineer sourdough complex fermentation. This study describes the population dynamics of five species of lactic acid bacteria-yeast communities in vitro using a generalized Lotka-Volterra model that examines interspecies interactions. A vulnerable yeast species was maintained within up to five species community dynamics by obtaining support with a cyclic interspecies interaction. Metaphorically, it involves a rock-paper-scissors game between two lactic acid bacteria species. Application of the generalized Lotka-Volterra model to real food microbiomes including sourdoughs will increase the reliability of the model prediction and help identify key microbial interactions that drive microbiome dynamics.

Longitudinal gut mycobiota changes in Japanese infants during first three years of life.

Although fungi can have a large impact on host health through the stimulation of the immune system and toxin production, few studies have investigated the gut mycobiota during infancy, a period during which sensitivity to internal and external stimuli is high. To capture the trend in fungal colonization during infancy, we evaluated the gut mycobiota of ten Japanese infants during the first 3 years of life. Infants had two major phyla, Ascomycota (68.9%) and Basidiomycota (29.6%), and the most abundant genus was Saccharomyces (26.8%), followed by Malassezia (18.5%), Candida (12.3%), Meyerozyma (8.5%), and Penicillium (8.3%). Alpha diversity analysis revealed a significant decrease in fungal richness and evenness with age, suggesting adaptive selection of the colonizing species in the gut environment. Beta diversity analysis divided infant mycobiota into age-related clusters and showed discrete separation before and after weaning, suggesting shift in microenvironment via weaning. In the initial stage, a variety of fungal species that likely originated from an environment, such as Malassezia spp., was highly colonized and were replaced by yeasts, such as Saccharomyces, after weaning. Further studies are needed to shed light on how the passage of the series of fungal colonizations in infancy affects the development of the host immune system and the other homeostasis involved in health later in life.

Pathobiont-responsive Th17 cells in gut-mouth axis provoke inflammatory oral disease and are modulated by intestinal microbiome.

Host immune response via Th17 cells against oral pathobionts is a key mediator in periodontitis development. However, where and how the Th17-type immune response is induced during the development of periodontitis is not well understood. Here, we demonstrate that gut translocation of the oral pathobiont Porphyromonas gingivalis (Pg) exacerbates oral pathobiont-induced periodontitis with enhanced Th17 cell differentiation. The oral pathobiont-responsive Th17 cells are differentiated in Peyer's patches and translocated systemically in the peripheral immune tissues. They are also capable of migrating to and accumulating in the mouth upon oral infection. Development of periodontitis via the oral pathobiont-responsive Th17 cells is regulated by the intestinal microbiome, and altering the intestinal microbiome composition with antibiotics affects the development of periodontitis. Our study highlights that pathobiont-responsive Th17 cells in the gut-mouth axis and the intestinal microbiome work together to provoke inflammatory oral diseases, including periodontitis.

The association between early formula and reduced risk of cow's milk allergy during the first three year of life: a Japanese cohort study.

BACKGROUND: Our recent observational study showed that regular consumption of cow's milk (CM) formula during early infancy (3-6 months old) was associated with a reduced risk of CM allergy (CMA) at 12 months old. However, the long-term association is unclear. The present study was aimed to examine how long this inverse association persists after 12 months old. METHODS: This study used the dataset of an ongoing nationwide prospective cohort, the Japan Environment and Children's Study, in which participants were registered between January 2011 and March 2014. We analyzed 65,568 children followed-up until 36 months old. The exposure factors were the consumption statuses of formula milk from 0-3, 3-6, and 6-12 months old. The primary outcome was the prevalence of CMA at 6, 12, 18, 24 and 36 months old. CMA was defined as an allergic reaction and sensitization to CM protein in an individual with no or limited intake of this protein at the evaluation time, combined with physician-diagnosed food allergy. Multivariable regression models were used to estimate the association between the periods of formula consumption and the prevalence of CMA. RESULTS: The prevalence of CMA increased with a peak of 1.51% at 18 months old and then declined to 0.79% at 36 months old. Formula milk from 3-6 months old was associated with a reduced risk of CMA throughout the first 3 years of life, although the extent of the reduction was mitigated with age (adjusted relative risk: [95% confidence interval]: 0.19 [0.10-0.34] at 12 months old, 0.23 [0.16-0.33] at 18 months old, 0.41 [0.26-0.64] at 24 months old, and 0.47 [0.26-0.80] at 36 months old). The association between early formula and CMA were observed in both children with and without eczema, but more prominent and long-lasting in the former than the latter. CONCLUSIONS: Regular exposure to CM protein during infancy was associated with a reduced prevalence of CMA during early childhood. At present, however, this observational study does not necessarily encourage formula feeding, and randomized controlled trials are warranted to confirm the findings and their significance.

Crisis of the Asian gut: associations among diet, microbiota, and metabolic diseases.

The increase of lifestyle-related diseases in Asia has recently become remarkably serious. This has been associated with a change in dietary habits that may alter the complex gut microbiota and its metabolic function in Asian people. Notably, the penetration of modern Western diets into Asia, which has been accompanied by an increase in fat content and decrease in plant-derived dietary fiber, is restructuring the Asian gut microbiome. In this review, we introduce the current status of obesity and diabetes in Asia and discuss the links of changes in dietary style with gut microbiota alterations which may predispose Asian people to metabolic diseases.

Assessment of bone health in patients with prostate cancer using cancer staging computed tomography.

PURPOSE: To evaluate the utility of vertebral Hounsfield unit (HU) values from computed tomography (CT) in cancer staging as a supplementary screening tool for bone health among prostate cancer (PCa) patients. METHODS: T-scores of bone mineral density (BMD) in each lumbar vertebra (L1-L4) and hip for newly diagnosed PCa patients (N = 139) were measured using dual-energy X-ray absorptiometry (DXA). The degenerative changes in each lumbar vertebra were assessed, and the HU values of trabecular bone in axial CT images of each vertebral body (vertebral CT-HU value) were measured using staging CT. RESULTS: 556 vertebrae were analyzed. 326 of 556 (59%) lumbar vertebrae had degenerative changes. The vertebral CT-HU value was positively correlated with the lumbar BMD T-score, with higher correlation coefficients observed in vertebrae without degenerative changes (r = 0.655, N = 230) when compared to vertebrae with degenerative changes (r = 0.575, N = 326). The thresholds matching BMD T-scores of - 2.0 and - 1.5 set by cancer treatment-induced bone loss guidelines were 95 HU and 105 HU, respectively. Based on the intervention threshold (lumbar BMD T-score < - 1.5), 15.1% of PCa patients required osteoporosis treatment; and, this value increased to 30.9% when L1-L4 CT-HU thresholds that corresponded to BMD T-score < - 1.5 were used. CONCLUSION: Lumbar BMD values from DXA may not reflect true bone health in PCa patients who often have lumbar degenerative diseases. Thresholds based on the vertebral CT-HU value can be used as a supplementary method to identify PCa patients who need anti-osteoporosis drugs.

Glucosylceramide Changes Bacterial Metabolism and Increases Gram-Positive Bacteria through Tolerance to Secondary Bile Acids In Vitro.

Glucosylceramide is present in many foods, such as crops and fermented foods. Most glucosylceramides are not degraded or absorbed in the small intestine and pass through the large intestine. Glucosylceramide exerts versatile effects on colon tumorigenesis, skin moisture, cholesterol metabolism and improvement of intestinal microbes in vivo. However, the mechanism of action has not yet been fully elucidated. To gain insight into the effect of glucosylceramide on intestinal microbes, glucosylceramide was anaerobically incubated with the dominant intestinal microbe, Blautia coccoides, and model intestinal microbes. The metabolites of the cultured broth supplemented with glucosylceramide were significantly different from those of broth not treated with glucosylceramide. The number of Gram-positive bacteria was significantly increased upon the addition of glucosylceramide compared to that in the control. Glucosylceramide endows intestinal microbes with tolerance to secondary bile acid. These results first demonstrated that glucosylceramide plays a role in the modification of intestinal microbes.

Secondary Metabolites of Actinomycetales as Potent Quorum Sensing Inhibitors Targeting Gram-Positive Pathogens: In Vitro and In Silico Study.

Anti-virulence agents are non-bacteriostatic and non-bactericidal emerging therapeutic options which hamper the production of virulence factors in pathogenic flora. In Staphylococcus aureus and Enterococcus faecalis, regulation of virulence genes' expression occurs through the cyclic peptide-mediated accessory gene regulator (agr) and its ortholog fsr quorum sensing systems, respectively. In the present study, we screened a set of 54 actinomycetales secondary metabolites as novel anti-virulence compounds targeting quorum sensing system of the Gram-positive bacteria. The results indicated that four compounds, Phenalinolactones A-D, BU-4664LMe, 4,5-dehydrogeldamycin, and Questinomycin A, potentially inhibit the agr quorum sensing system and hemolytic activity of S. aureus. On the other hand, Decatromicin A and B, Okilactomycin, Rishirilide A, Abyssomicin I, and Rebeccamycin selectively blocked the fsr quorum sensing system and the gelatinase production in E. faecalis at sub-lethal concentrations. Interestingly, Synerazol uniquely showed the capability to inhibit both fsr and agr quorum sensing systems. Further, in silico molecular docking studies were performed which provided closer insights into the mode of action of these compounds and proposed that the inhibitory activity of these compounds could be attributed to their potential ability to bind to the ATP-active site of S. aureus AgrA. Taken together, our study highlights the potential of actinomycetales secondary metabolites with diverse structures as anti-virulence quorum sensing inhibitors.

Characterization and Demonstration of Mock Communities as Control Reagents for Accurate Human Microbiome Community Measurements.

Standardization and quality assurance of microbiome community analysis by high-throughput DNA sequencing require widely accessible and well-characterized reference materials. Here, we report on newly developed DNA and whole-cell mock communities to serve as control reagents for human gut microbiota measurements by shotgun metagenomics and 16S rRNA gene amplicon sequencing. The mock communities were formulated as near-even blends of up to 20 bacterial species prevalent in the human gut, span a wide range of genomic guanine-cytosine (GC) contents, and include multiple strains with Gram-positive type cell walls. Through a collaborative study, we carefully characterized the mock communities by shotgun metagenomics, using previously developed standardized protocols for DNA extraction and sequencing library construction. Further, we validated fitness of the mock communities for revealing technically meaningful differences among protocols for DNA extraction and metagenome/16S rRNA gene amplicon library construction. Finally, we used the mock communities to reveal varying performance of metagenome-based taxonomic profilers and the impact of trimming and filtering of sequencing reads on observed species profiles. The latter showed that aggressive preprocessing of reads may result in substantial GC-dependent bias and should thus be carefully evaluated to minimize unintended effects on species abundances. Taken together, the mock communities are expected to support a myriad of applications that rely on well-characterized control reagents, ranging from evaluation and optimization of methods to assessment of reproducibility in interlaboratory studies and routine quality control. IMPORTANCE Application of high-throughput DNA sequencing has greatly accelerated human microbiome research and its translation into new therapeutic and diagnostic capabilities. Microbiome community analyses results can, however, vary considerably across studies or laboratories, and establishment of measurement standards to improve accuracy and reproducibility has become a priority. The here-developed mock communities, which are available from the NITE Biological Resource Center (NBRC) at the National Institute of Technology and Evaluation (NITE, Japan), provide well-characterized control reagents that allow users to judge the accuracy of their measurement results. Widespread and consistent adoption of the mock communities will improve reproducibility and comparability of microbiome community analyses, thereby supporting and accelerating human microbiome research and development.

Bile acid dysmetabolism in the gut-microbiota-liver axis under hepatitis C virus infection.

BACKGROUND & AIMS: We recently analysed and reported the features of the micro biome under hepatitis C virus (HCV) infection, but the effect of HCV infection on bile acid (BA) metabolism in the gut-liver axis remains poorly understood. The aim of this study was to clarify the characteristics of the gut-liver axis in HCV-infected patients. METHODS: The faecal BAs composition and gut microbiota from 100 chronic hepatitis C (CHC) patients were compared with those from 23 healthy individuals. For transcriptional analysis of the liver, 22 mild CHC (fibrosis stages [F] 0-2) and 42 advanced CHC (F3-4) cases were compared with 12 healthy individuals. The findings were confirmed using chimeric mice with human hepatocytes infected with HCV HCR6. RESULTS: Chronic hepatitis C patients, even at earlier disease stages, showed BA profiles distinct from healthy individuals, in which faecal deoxycholic acid (DCA) was significantly reduced and lithocholic acid or ursodeoxycholic acid became dominant. The decrease in faecal DCA was correlated with reduction in commensal Clostridiales and increase in oral Lactobacillales. Impaired biosynthesis of cholic acid (CA) was observed as a reduction in the transcription level of cytochrome P450 8B1 (CYP8B1), a key enzyme in CA biosynthesis. The reductions in faecal DCA and liver CYP8B1 were also observed in HCV-infected chimeric mice. CONCLUSIONS: Chronic hepatitis C alters the intestinal BA profile, in association with the imbalance of BA biosynthesis, which differs from the pattern in NAFLD. These imbalances appear to drive disease progression through the gut-microbiome-liver axis.

Gut microbiome status of urban and rural Filipino adults in relation to diet and metabolic disorders.

Here, we aim to understand the condition of the gut microbiome of Filipino adults in relation to their diet and metabolic status. Compared to rural Albay (n = 67), the gut microbiome of subjects living in urban Manila (n = 25) was more colonized by the order Clostridiales, which was negatively correlated with host carbohydrate consumption. Principal component analysis using the genus composition of the 92 total subjects indicated four microbiome types: one type driven by Prevotella, which was associated with high rice consumption and mainly consisted of healthy Albay subjects, one Clostridiales-driven group containing a number of type 2 diabetes mellitus (T2D) subjects from both Manila and Albay who showed lower butyrate levels in association with a decrease in Mediterraneibacter faecis, and the other two types showing dysbiosis-like microbiomes with Lactobacillus and Bifidobacterium overgrowth, with a high ratio of T2D and obese subjects. Multivariate logistic regression analysis suggested high dietary energy intake, and two Veillonellaeae genera, Dialister and Megasphaera, as T2D risk factors, while Prevotella and M. faecis as anti-T2D factors. In conclusion, low-carbohydrate diets restructured the Prevotella-driven gut microbiome, which may predispose Filipino people with high energy diet to T2D.

Characterization of the Biosynthetic Gene Cluster of Enterocin F4-9, a Glycosylated Bacteriocin.

Enterocin F4-9 belongs to the glycocin family having post-translational modifications by two molecules of N-acetylglucosamine ß-O-linked to Ser37 and Thr46. In this study, the biosynthetic gene cluster of enterocin F4-9 was cloned and expressed in Enterococcus faecalis JH2-2. Production of glycocin by the JH2-2 expression strain was confirmed by expression of the five genes. The molecular weight was greater than glycocin secreted by the wild strain, E. faecalis F4-9, because eight amino acids from the N-terminal leader sequence remained attached. This N-terminal extension was eliminated after treatment with the culture supernatant of strain F4-9, implying an extracellular protease from E. faecalis F4-9 cleaves the N-terminal sequence. Thus, leader sequences cleavage requires two steps: the first via the EnfT protease domain and the second via extracellular proteases. Interestingly, the long peptide, with N-terminal extension, demonstrated advanced antimicrobial activity against Gram-positive and Gram-negative bacteria. Furthermore, enfC was responsible for glycosylation, a necessary step prior to secretion and cleavage of the leader peptide. In addition, enfI was found to grant self-immunity to producer cells against enterocin F4-9. This report demonstrates specifications of the minimal gene set responsible for production of enterocin F4-9, as well as a new biosynthetic mechanism of glycocins.

Mechanistic Insight into Yeast Bloom in a Lactic Acid Bacteria Relaying-Community in the Start of Sourdough Microbiota Evolution.

The spontaneous microbiota of wheat sourdough, often comprising one yeast species and several lactic acid bacteria (LAB) species, evolves over repeated fermentation cycles, which bakers call backslopping. The final product quality largely depends on the microbiota functions, but these fluctuate sometimes during the initial months of fermentation cycles due to microbiota evolution in which three phases of LAB relay occur. In this study, the understanding of yeast-LAB interactions in the start of the evolution of the microbiota was deepened by exploring the timing and trigger interactions when sourdough yeast entered a preestablished LAB-relaying community. Monitoring of 32 cycles of evolution of 6 batches of spontaneous microbiota in wheat sourdoughs revealed that sourdough yeasts affected the LAB community when the 2nd- or 3rd-relaying types of LAB genera emerged. In in vitro pairwise cocultures, all 12 LAB strains containing the 3 LAB-relaying types arrested the growth of a Saccharomyces cerevisiae strain, a frequently found species in sourdoughs, to various extents by sugar-related interactions. These findings suggest competition due to different affinities of each LAB and a S. cerevisiae strain for each sugar. In particular, maltose was the driver of S. cerevisiae growth in all pairwise cocultures. The functional prediction of sugar metabolism in sourdough LAB communities showed a positive correlation between maltose degradation and the yeast population. Our results suggest that maltose-related interactions are key factors that enable yeasts to enter and then settle in the LAB-relaying community during the initial part of evolution of spontaneous sourdough microbiota. IMPORTANCE Unpredictable evolution of spontaneous sourdough microbiota sometimes prevents bakers from making special-quality products because the unstable microbiota causes the product quality to fluctuate. Elucidation of the evolutionary mechanisms of the sourdough community, comprising yeast and lactic acid bacteria (LAB), is fundamental to control fermentation performance. This study investigated the mechanisms by which sourdough yeasts entered and settled in a bacterial community in which a three-phase relay of LAB occurred. Our results showed that all three layers of LAB restricted the cohabiting yeast population by competing for the sugar sources, particularly maltose. During the initial evolution of spontaneous sourdough microbiota, yeasts tended to grow synchronously with the progression of the lactic acid bacterial relay, which was predictably associated with changes in the maltose degradation functions in the bacterial community. Further study of ≥3 species' interactions while considering yeast diversity can uncover additional interaction mechanisms driving the initial evolution of sourdough microbiota.

Cultivation of Spore-Forming Gut Microbes Using a Combination of Bile Acids and Amino Acids.

Spores of certain species belonging to Firmicutes are efficiently germinated by nutrient germinators, such as amino acids, in addition to bile acid. We attempted to culture difficult-to-culture or yet-to-be cultured spore-forming intestinal bacteria, using a combination of bile acids and amino acids. The combination increased the number of colonies that formed on agar medium plated with ethanol-treated feces. The operational taxonomic units of these colonized bacteria were classified into two types. One type was colonized only by the bile acid (BA) mixture and the other type was colonized using amino acids, in addition to the BA mixture. The latter contained 13 species, in addition to 14 species of the former type, which mostly corresponds to anaerobic difficult-to-culture Clostridiales species, including several new species candidates. The use of a combination of BAs and amino acids effectively increased the culturability of spore-forming intestinal bacteria.

Mucosa-associated gut microbiota reflects clinical course of ulcerative colitis.

This longitudinal study was designed to elucidate whether gut microbiota is associated with relapse and treatment response in ulcerative colitis (UC) patients. Fifty-one patients with UC were enrolled between 2012 and 2017, and followed up through 2020. Colon mucosal biopsy were obtained at enrollment, and 16S ribosomal RNA sequencing was performed using extracted RNA. Of the 51 patients, 24 were in remission and 27 had active UC at enrollment. Of the 24 patients in remission, 17 maintained remission and 7 developed relapse during follow-up. The 7 patients with relapse showed lower diversity, with a lower proportion of Clostridiales (p = 0.0043), and a higher proportion of Bacteroides (p = 0.047) at enrollment than those without relapse. The 27 patients with active UC were classified into response (n = 6), refractory (n = 13), and non-response (n = 8) groups according to their treatment response in 6 months. The refractory and non-response groups showed lower diversity with a lower proportion of Prevotella (p = 0.048 and 0.043) at enrollment than the response group. This study is the first demonstration that reduced diversity and particular microbes are associated with the later clinical course of relapse events and treatment response in UC.

Gut Microbiome of Indonesian Adults Associated with Obesity and Type 2 Diabetes: A Cross-Sectional Study in an Asian City, Yogyakarta.

Indonesia is a developing country facing the national problem of the growing obesity and diabetes in its population due to recent drastic dietary and lifestyle changes. To understand the link between the gut microbiome, diet, and health of Indonesian people, fecal microbiomes and metabolomes of 75 Indonesian adults in Yogyakarta City, including obese people (n = 21), type 2 diabetes (T2D) patients (n = 25), and the controls (n = 29) were characterized together with their dietary and medical records. Variations of microbiomes showed a triangular distribution in the principal component analysis, driven by three dominant bacterial genera, namely Bacteroides, Prevotella, and Romboutsia. The Romboutsia-driven microbiome, characterized by low bacterial diversity and high primary bile acids, was associated with fat-driven obesity. The Bacteroides-driven microbiome, which counteracted Prevotella but was associated with Ruminococcaceae concomitantly increased with high-carbohydrate diets, showed positive correlation with T2D indices but negative correlation with body mass index. Notably, Bacteroides fragilis was increased in T2D patients with a decrease in fecal conjugated bile acids, particularly tauroursodeoxycholic acid (TUDCA), a farnesoid X receptor (FXR) antagonist with anti-diabetic activity, while these features disappeared in patients administered metformin. These results indicate that the gut microbiome status of Indonesian adults is differently associated with obesity and T2D under their varied dietary habits.

[A Case of Adrenal Anastomosing Hemangioma].

An 83-year-old man with left lower back pain was found to have a 5 cm mass in contact with the right adrenal gland and a 12 mm left ureteral stone by abdominal plain computed tomography. An abdominal plain magnetic resonance imaging T2-weighted image revealed a heterogeneous high signal mass in the right adrenal gland. Pheochromocytoma, adrenal carcinoma, and retroperitoneal neurogenic tumor were suspected. Tumor markers and endocrine examinations were within standard values. Laparoscopic right adrenalectomy was performed. A 4×3.6 cm, 62 g solid tumor was found in contact with right adrenal gland. Histopathologically, hobnail-like vascular endothelial cells were found in the tumor, but no malignant findings such as multi-layered vascular endothelial cells and nuclear atypia were observed. This tumorwas diagnosed to be an anastomosing hemangioma.