Gut microbiota from patients with Parkinson's disease causes motor deficits in honeybees.

Objective: Parkinson's disease (PD) is possibly caused by genetic factors, environmental factors, and gut microbiota dysbiosis. This study aims to explore whether the microbiota contributes to the behavior abnormalities of PD. Methods: We transplanted gut microbiota from patients with PD or healthy controls (HC) into microbiota-free honeybees. We also established two more groups, namely the rotenone (ROT) group, in which PD-like symptoms of honeybees were induced by rotenone, and the conventional (CV) group, in which honeybees were colonized with conventional gut microbiota. The climbing assay was performed to assess the motor capabilities of honeybees. Histopathological examination was conducted to evaluate the integrity of gut mucosa. Tyrosine hydroxylase (TH) gene expression levels and dopamine (DA) concentrations in the brain were also examined. Additionally, metagenomics and full-length 16S rRNA analyses were performed to identify alterations in gut microbiota profiles, both in PD patients and honeybees. Results: Honeybees in the PD and ROT groups exhibited slower climbing speeds, downregulated TH gene expression, and impaired gut barriers. Both the HC and PD groups of honeybees successfully harbored a portion of gut microbiota from corresponding human donors, and differences in microbial composition were identified. Morganella morganii and Erysipelatoclostridium ramosum exhibited significantly increased relative abundance in the HC group, while Dorea longicatena, Collinsella aerofaciens, Lactococcus garvieae, Holdemanella biformis, Gemmiger formicilis, and Blautia obeum showed significantly increased relative abundance in the PD group. Functional predictions of microbial communities in the PD group indicated an increased synthesis of hydrogen sulfide and methane. Conclusion: A novel PD model was induced in honeybees with rotenone and gut microbiota from PD patients. This study linked PD-related behaviors to altered gut microbiota, highlighting a potential gut microbiota-brain axis involvement in PD pathogenesis. We identify previously unrecognized associations of Dorea longicatena, Collinsella aerofaciens, Lactococcus garvieae, Holdemanella biformis, Gemmiger formicilis, and Blautia obeum with PD. Additionally, pathways related to hydrogen sulfide and methane synthesis have been previously suggested as potential contributors to the development of PD, and our research further supports this hypothesis.

Update of gut gas metabolism in ulcerative colitis.

INTRODUCTION: Ulcerative colitis (UC) is a chronic, nonspecific inflammatory disease of the intestine. The intestinal microbiota is essential in the occurrence and development of UC. Gut gases are produced via bacterial fermentation or chemical interactions, which can reveal altered intestinal microbiota, abnormal cellular metabolism, and inflammation responses. Recent studies have demonstrated that UC patients have an altered gut gas metabolism. AREAS COVERED: In this review, we integrate gut gas metabolism advances in UC and discuss intestinal gases' clinical values as new biomarkers or therapeutic targets for UC, providing the foundation for further research. Literature regarding gut gas metabolism and its significance in UC from inception to October 2023 was searched on the MEDLINE database and references from relevant articles were investigated. EXPERT OPINION: Depending on their type, concentration, and volume, gut gases can induce or alleviate clinical symptoms and regulate intestinal motility, inflammatory responses, immune function, and oxidative stress, significantly impacting UC. Gut gases may function as new biomarkers and provide potential diagnostic or therapeutic targets for UC.

Siderophore-harboring gut bacteria and fecal siderophore genes for predicting the responsiveness of fecal microbiota transplantation for active ulcerative colitis.

BACKGROUND: Predictive markers for fecal microbiota transplantation (FMT) outcomes in patients with active ulcerative colitis (UC) are poorly defined. We aimed to investigate changes in gut microbiota pre- and post-FMT and to assess the potential value in determining the total copy number of fecal bacterial siderophore genes in predicting FMT responsiveness. METHODS: Patients with active UC (Mayo score ≥ 3) who had undergone two FMT procedures were enrolled. Fecal samples were collected before and 8 weeks after each FMT session. Patients were classified into clinical response and non-response groups, based on their Mayo scores. The fecal microbiota profile was accessed using metagenomic sequencing, and the total siderophore genes copy number via quantitative real-time polymerase chain reaction. Additionally, we examined the association between the total siderophore genes copy number and FMT efficacy. RESULTS: Seventy patients with UC had undergone FMT. The clinical response and remission rates were 50% and 10% after the first FMT procedure, increasing to 72.41% and 27.59% after the second FMT. The cumulative clinical response and clinical remission rates were 72.86% and 25.71%. Compared with baseline, the response group showed a significant increase in Faecalibacterium, and decrease in Enterobacteriaceae, consisted with the changes of the total bacterial siderophore genes copy number after the second FMT (1889.14 vs. 98.73 copies/ng, P < 0.01). Virulence factor analysis showed an enriched iron uptake system, especially bacterial siderophores, in the pre-FMT response group, with a greater contribution from Escherichia coli. The total baseline copy number was significantly higher in the response group than non-response group (1889.14 vs. 94.86 copies/ng, P < 0.01). A total baseline copy number cutoff value of 755.88 copies/ng showed 94.7% specificity and 72.5% sensitivity in predicting FMT responsiveness. CONCLUSIONS: A significant increase in Faecalibacterium, and decrease in Enterobacteriaceae and the total fecal siderophore genes copy number were observed in responders after FMT. The siderophore genes and its encoding bacteria may be of predictive value for the clinical responsiveness of FMT to active ulcerative colitis.

Advances in the isolation, cultivation, and identification of gut microbes.

The gut microbiome is closely associated with human health and the development of diseases. Isolating, characterizing, and identifying gut microbes are crucial for research on the gut microbiome and essential for advancing our understanding and utilization of it. Although culture-independent approaches have been developed, a pure culture is required for in-depth analysis of disease mechanisms and the development of biotherapy strategies. Currently, microbiome research faces the challenge of expanding the existing database of culturable gut microbiota and rapidly isolating target microorganisms. This review examines the advancements in gut microbe isolation and cultivation techniques, such as culturomics, droplet microfluidics, phenotypic and genomics selection, and membrane diffusion. Furthermore, we evaluate the progress made in technology for identifying gut microbes considering both non-targeted and targeted strategies. The focus of future research in gut microbial culturomics is expected to be on high-throughput, automation, and integration. Advancements in this field may facilitate strain-level investigation into the mechanisms underlying diseases related to gut microbiota.

Fecal microbiota transplantation significantly improved respiratory failure of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that leads to respiratory failure, and eventually death. However, there is a lack of effective treatments for ALS. Here we report the results of fecal microbiota transplantation (FMT) in two patients with late-onset classic ALS with a Japan ALS severity classification of grade 5 who required tracheostomy and mechanical ventilation. In both patients, significant improvements in respiratory function were observed following two rounds of FMT, leading to weaning off mechanical ventilation. Their muscle strength improved, allowing for assisted standing and mobility. Other notable treatment responses included improved swallowing function and reduced muscle fasciculations. Metagenomic and metabolomic analysis revealed an increase in beneficial Bacteroides species (Bacteroides stercoris, Bacteroides uniformis, Bacteroides vulgatus), and Faecalibacterium prausnitzii after FMT, as well as elevated levels of metabolites involved in arginine biosynthesis and decreased levels of metabolites involved in branched-chain amino acid biosynthesis. These findings offer a potential rescue therapy for ALS with respiratory failure and provide new insights into ALS in general.

Dynamic changes in the gut microbiota after bismuth quadruple therapy and high-dose dual therapy for Helicobacter pylori eradication.

BACKGROUND: A novel regimen with high-dose dual therapy (HDDT) has emerged, but its impact on the gut microbiota is not well understood. This study aimed to evaluate the impact of HDDT on the gut microbiota and compare it with that of bismuth quadruple therapy (BQT). METHODS: We enrolled outpatients (18-70 years) diagnosed with Helicobacter pylori infection by either histology or a positive 13C-urea breath test (13C-UBT) and randomly assigned to either the BQT or HDDT group. Subjects consented to provide fecal samples which were collected at baseline, Week 2, and Week 14. Amplification of the V1 and V9 regions of the 16S rRNA was conducted followed by high-throughput sequencing. RESULTS: Ultimately, 78 patients (41 patients in the HDDT group and 37 in the BQT group) were enrolled in this study. Eradication therapy significantly altered the diversity of the gut microbiota. However, the alpha diversity rebounded only in the HDDT group at 12 weeks post-eradication. Immediately following eradication, the predominance of Proteobacteria, replacing commensal Firmicutes and Bacteroidetes, did not recover after 12 weeks. Species-level analysis showed that the relative abundances of Klebsiella pneumoniae and Escherichia fergusonii significantly increased in both groups at Week 2. Enterococcus faecium and Enterococcus faecalis significantly increased in the BQT group, with no significant difference observed in the HDDT group. After 12 weeks of treatment, the relative abundance of more species in the HDDT group returned to baseline levels. CONCLUSION: Eradication of H. pylori can lead to an imbalance in gut microbiota. Compared to BQT, the HDDT is a regimen with milder impact on gut microbiota.

Identification of mapk genes, and their expression profiles in response to low salinity stress, in cobia (Rachycentron canadum).

Mitogen-activated protein kinases (MAPKs) are a class of protein kinases that regulate various physiological processes, and play a crucial role in maintaining the osmotic equilibrium of fish. The objective of this study was to identify and characterize the mapk family genes in cobia (Rachycentron canadum) and examine their expression profiles under different low salinity stress regimes (acute: from 30‰ to 10‰ in 1 h, sub-chronic: from 30‰ to 10‰ over 4 d). A total of 12 cobia mapk genes (Rcmapks) were identified and cloned, including six erk subfamily genes (Rcmapk1/3/4/6/7/15), three jnk subfamily genes (Rcmapk8/9/10) and three p38 mapk subfamily genes (Rcmapk 11/13/14). Domain analysis indicated that the RcMAPKs possessed the typical domains including S_TKc and PKc_like domain. Phylogenetic analysis revealed that the Rcmapks were most closely related to those of the turbot (Scophthalmus maximus). The tissue distribution of mapk genes in adult cobia and the expression patterns of Rcmapks under different low salinity stress regimes were investigated using quantitative real-time PCR (qRT-PCR). The results revealed that Rcmapk3/9/10/11/13/14 exhibited a relatively broad expression distribution across 14 different tissues. For all these genes the highest expression level was in the brain, except for Rcmapk14 (highly expressed in the stomach, gill, and skin). The genes Rcmapk1/6/15 showed significantly higher expression in the testis. Under acute low salinity stress, expression of Rcmapk1/3/6/7/9/11/13/14 was significantly altered in the gill, intestine, and trunk kidney, however, the aforementioned genes exhibited very different expression patterns among the three tissues. In the gill, most of the genes from the erk (Rcmapk3/6/7) and p38 mapk subfamily (Rcmapk11/13/14) were significantly up-regulated at almost all the time points (P < 0.05); Similarly, the expression of Rcmapk3/9/11/13/14 genes were significantly increased in the trunk kidney; while in the intestine, most of the altered genes (Rcmapk6/7/9/11/13/14) were significantly down-regulated at 1 h. Following the sub-chronic low salinity stress, expression of Rcmapk1/3/6/7/9/11/13/14 genes were significantly altered in all three tissues. These findings provide important reference data for elucidating the roles of cobia mapk family genes in response to low salinity stress.

Sleep deprivation-induced anxiety-like behaviors are associated with alterations in the gut microbiota and metabolites.

The present study aimed to characterize the gut microbiota and serum metabolome changes associated with sleep deprivation (SD) as well as to explore the potential benefits of multi-probiotic supplementation in alleviating SD-related mental health disorders. Rats were subjected to 7 days of SD, followed by 14 days of multi-probiotics or saline administration. Open-field tests were conducted at baseline, end of SD (day 7), and after 14 days of saline or multi-probiotic gavage (day 21). Metagenomic sequencing was conducted on fecal samples, and serum metabolites were measured by untargeted liquid chromatography tandem-mass spectrometry. At day 7, anxiety-like behaviors, including significant decreases in total movement distance (P = 0.0002) and staying time in the central zone (P = 0.021), were observed. In addition, increased levels of lipopolysaccharide (LPS; P = 0.028) and decreased levels of uridine (P = 0.018) and tryptophan (P = 0.01) were detected in rats after 7 days of SD. After SD, the richness of the gut bacterial community increased, and the levels of Akkermansia muciniphila, Muribaculum intestinale, and Bacteroides caecimuris decreased. The changes in the host metabolism and gut microbiota composition were strongly associated with the anxiety-like behaviors caused by SD. In addition, multi-probiotic supplementation for 14 days modestly improved the anxiety-like behaviors in SD rats but significantly reduced the serum level of LPS (P = 0.045). In conclusion, SD induces changes in the gut microbiota and serum metabolites, which may contribute to the development of chronic inflammatory responses and affect the gut-brain axis, causing anxiety-like behaviors. Probiotic supplementation significantly reduces serum LPS, which may alleviate the influence of chronic inflammation. IMPORTANCE: The disturbance in the gut microbiome and serum metabolome induced by SD may be involved in anxiety-like behaviors. Probiotic supplementation decreases serum levels of LPS, but this reduction may be insufficient for alleviating SD-induced anxiety-like behaviors.

Categorization of the effects of E. coli LF82 and mutants lacking the chuT and shuU genes on survival, the transcriptome, and metabolome in germ-free honeybee.

The precise etiology of inflammatory bowel diseases (IBDs) remains elusive. The Escherichia coli strain LF82 (LF82) is known to be associated with IBD, and we hypothesized that this association may be related to the chuT and shuU genes. Here we constructed a germ-free (GF) honeybee model to investigate the effects of LF82 chuT and shuU genes on the honeybee intestine and their mechanisms. The chuT and shuU gene deletion strains LF82∆chuT and LF82∆shuU were generated by CRISPR-Cas9. These strains, together with nonpathogenic E. coli MG1655 (MG1655) and wildtype LF82, were allowed to colonize the guts of GF honeybees to establish single bacterial colonization models. Intestinal permeability was assessed following the administration of a sterile Brilliant Blue (FCF) solution. Comprehensive transcriptomic and metabolomic analyses of intestinal samples indicated that MG1655 had few disadvantageous effects on honeybees. Conversely, colonization with LF82 and its gene-deletion mutants provoked pronounced activation of genes associated with innate immune pathways, stimulated defensive responses, and induced expression of genes associated with inflammation, oxidative stress, and glycosaminoglycan degradation. Crucially, the LF82∆chuT and LF82∆shuU strains perturbed host heme and iron regulation, as well as tryptophan metabolism. These findings suggest that the deletion of chuT and shuU genes in E. coli LF82 may alleviate intestinal inflammation by partially modulating tryptophan catabolism. Our study proposes that targeting iron uptake mechanisms could be a potential strategy to mitigate the virulence of IBD-associated bacteria.

Crohn's disease-associated Escherichia coli LF82 in the gut damage of germ-free honeybees: A laboratory study.

Escherichia coli LF82 (LF82) is associated with Crohn's disease. The simplicity and genetic maneuverability of honeybees' gut microbiota make them suitable for studying host-microbe interactions. To understand the interaction between LF82 and host gut, LF82 was used to infect germ-free honeybees (Apis mellifera) orally. We found that LF82 successfully colonized the gut and shortened the lifespan of germ-free bees. LF82 altered the gut structure and significantly increased gut permeability. RT-qPCR showed that LF82 infection activated anti-infective immune pathways and upregulated the mRNAs levels of antimicrobial peptides in the gut of germ-free bees. The gut transcriptome showed that LF82 significantly upregulated genes involved in Notch signaling, adhesion junctions, and Toll and Imd signaling pathways and downregulated genes involved in the peroxisome proliferator-activated receptor (PPAR) signaling pathway, protein digestion and absorption, and tyrosine metabolism. In conclusion, the human-derived enteropathogenic bacterium LF82 can successfully colonize the gut of germ-free honeybees and cause enteritis-like changes, which provides an ideal model organism for revealing the pathogenesis of bacterial-associated diseases.

The fecal microbiota from children with autism impact gut metabolism and learning and memory abilities of honeybees.

Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders, with an increasing incidence. Gastrointestinal symptoms are common comorbidities of ASD. The gut microbiota composition of children with autism is distinct from that of typical developmental (TD) children, suggesting that the gut microbiota probably influences on hosts via the microbiota-gut-brain axis. However, the relationship between intestinal dysbiosis and host brain function remains unclear. In this study, we creatively developed a honeybee model and investigated the potential effects of fecal microbiota on hosts. Fecal microbiota from children with autism and TD children were transplanted into microbiota-free honeybees (Apis mellifera), resulting in induced ASD-fecal microbiota transplantation (FMT) honeybees (A-BEE group) and TD-FMT honeybees (T-BEE group), respectively. We found that cognitive abilities of honeybees in the A-BEE group were significantly impaired in olfactory proboscis extension response conditioning. Metagenomics was used to evaluate fecal microbiota colonization, revealing several differential species responsible for altered tryptophan metabolism and taurine metabolism within the bee gut, including Bacteroides dorei, Bacteroides fragilis, Lactobacillus gasseri, and Lactobacillus paragasseri. Furthermore, fecal microbiota from children with autism downregulated brain genes involved in neural signaling and synaptic transmission within honeybees. Notably, differentially spliced genes observed within brains of honeybees from the A-BEE group largely overlapped with those identified in human diagnosed with autism via SFARI and SPARK gene sets. These differentially spliced genes were also enriched within pathways related to neural synaptic transmission. Our findings provide novel insights into the pivotal role of the human gut microbiota, which may contribute to neurological processes in honeybees. Additionally, we present a few research sources on gut-brain connections in ASD.

Prognostic models based on lymph node density for primary gastrointestinal melanoma: a SEER population-based analysis.

OBJECTIVE: This study aimed to construct prognostic models to predict the overall survival (OS) and cancer-specific survival (CSS) of patients with primary gastrointestinal melanoma (PGIM). DESIGN: An observational and retrospective study. SETTING: Data were obtained from the Surveillance, Epidemiology and End Results (SEER) programme database, encompassing a broad geographical and demographic spectrum of patients across the USA. PARTICIPANTS: A total of 991 patients diagnosed with PGIM were included in this study. METHODS: A total of 991 patients with PGIM were selected from the SEER database. They were further divided into a training cohort and a validation cohort. Independent prognostic factors were identified by Cox regression analysis. Two prognostic models were constructed based on the results of multivariable Cox regression analysis. The concordance index (C-index) and area under the time-dependent receiver operating characteristic curve (time-dependent AUC) were used to evaluate the discriminative ability. Calibration curves were plotted to evaluate the agreement between the probability as predicted by the models and the actual probability. Risk stratification was developed given the model. RESULTS: By the multivariable Cox regression analysis, we identified four independent risk factors (age, stage, lymph node density and surgery) for OS, and three independent risk factors (stage, lymph node density and surgery) for CSS, which were used to construct prognostic models. C-index, time-dependent AUC, calibration curves and Kaplan-Meier curves of risk stratification indicated that these two models had good discriminative ability, predictive ability as well as clinical value. CONCLUSIONS: The prognostic models of OS and CSS had satisfactory accuracy and were of clinical value in evaluating the prognosis of patients with PGIM.

Proton pump inhibitors induced fungal dysbiosis in patients with gastroesophageal reflux disease.

Gut mycobiota inhabits human gastrointestinal lumen and plays a role in human health and disease. We investigated the influence of proton pump inhibitors (PPIs) on gastric mucosal and fecal mycobiota in patients with gastroesophageal reflux diseases (GERD) by using Internal Transcribed Spacer 1 sequencing. A total of 65 participants were included, consisting of the healthy control (HC) group, GERD patients who did not use PPIs (nt-GERD), and GERD patients who used PPIs, which were further divided into short-term (s-PPI) and long-term PPI user (l-PPI) groups based on the duration of PPI use. The alpha diversity and beta diversity of gastric mucosal mycobiota in GERD patients with PPI use were significantly different from HCs, but there were no differences between s-PPI and l-PPI groups. LEfSe analysis identified Candida at the genus level as a biomarker for the s-PPI group when compared to the nt-GERD group. Meanwhile, Candida, Nothojafnea, Rhizodermea, Ambispora, and Saccharicola were more abundant in the l-PPI group than in the nt-GERD group. Furthermore, colonization of Candida in gastric mucosa was significantly increased after PPI treatment. However, there was no significant difference in Candida colonization between patients with endoscopic esophageal mucosal breaks and those without. There were significant differences in the fecal mycobiota composition between HCs and GERD patients regardless whether or not they used PPI. As compared to nt-GERD patient samples, there was a high abundance of Alternaria, Aspergillus, Mycenella, Exserohilum, and Clitopilus in the s-PPI group. In addition, there was a significantly higher abundance of Alternaria, Aspergillus, Podospora, Phallus, and Monographella in the l-PPI group than nt-GERD patients. In conclusion, our study indicates that dysbiosis of mycobiota was presented in GERD patients in both gastric mucosal and fecal mycobiota. PPI treatment may increase the colonization of Candida in the gastric mucosa in GERD patients.

Lactobacillus oris improves non-alcoholic fatty liver in mice and inhibits endogenous cholesterol biosynthesis.

We previously confirmed that a strain of Lactobacillus oris isolated from the fecal samples of healthy Hainan centenarian having potent lipid-lowering ability in HepG2 cells; and this study was to investigate the effect of the stain on non-alcoholic fatty liver in mice in vivio. The Lactobacillus oris strain isolated from Hainan centenarian fecal samples were frozen stored in our laboratory. Thirty ob/ob mice (10 in each group) were orally gavaged with Lactobacillus oris (Lactobacillus, 5 × 109 cfu), mixed probiotics (Mixed, 5 × 109 cfu, a mixture with known lipid-lowering ability), or culture medium (Control) respectively. Lactobacillus oris isolated from fecal samples of Hainan centenarians showed significantly in vivo lipid lowering ability compared with the controls, and the ability was comparable with mixed probiotics strains in mice The possible mechanisms of lipid-lowering of probiotics and Lactobacillus oris may be associated with HMGR inhibition to suppress the synthesis of endogenous cholesterol; bile acids reabsorption, and intestinal FXR-FGF15 signaling pathways promoting the cholesterol conversion into bile acids secretion.

Colorectal cancer and gut microbiota studies in China.

Colorectal cancer (CRC) is the third most common malignant tumor worldwide. The incidence and mortality rates of CRC have been increasing in China, possibly due to economic development, lifestyle, and dietary changes. Evidence suggests that gut microbiota plays an essential role in the tumorigenesis of CRC. Gut dysbiosis, specific pathogenic microbes, metabolites, virulence factors, and microbial carcinogenic mechanisms contribute to the initiation and progression of CRC. Gut microbiota biomarkers have potential translational applications in CRC screening and early diagnosis. Gut microbiota-related interventions could improve anti-tumor therapy's efficacy and severe intestinal toxic effects. Chinese researchers have made many achievements in the relationship between gut microbiota and CRC, although some challenges remain. This review summarizes the current evidence from China on the role of gut microbiota in CRC, mainly including the gut microbiota characteristics, especially Fusobacterium nucleatum and Parvimonas micra, which have been identified to be enriched in CRC patients; microbial pathogens such as F. nucleatum and enterotoxigenic Bacteroides fragilis, and P. micra, which Chinese scientists have extensively studied; diagnostic biomarkers especially F. nucleatum; therapeutic effects, including microecological agents represented by certain Lactobacillus strains, fecal microbiota transplantation, and traditional Chinese medicines such as Berberine and Curcumin. More efforts should be focused on exploring the underlying mechanisms of microbial pathogenesis of CRC and providing novel gut microbiota-related therapeutic and preventive strategies.

Chinese expert consensus on the application of live combined Bifidobacterium, Lactobacillus, and Enterococcus powder/capsule in digestive system diseases (2021).

BACKGROUND AND AIM: Disturbance of gut microbiota is associated with pathological change in multiple diseases. Probiotics can improve symptoms and exert clinical effects via regulation of gastrointestinal microecological environments, and a probiotic product commonly dispensed by Chinese physicians is a combination of live Bifidobacterium, Lactobacillus, and Enterococcus in powder/capsule form. It contains three strains-of Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis-which can act synergistically to balance the microbiome, regulate immunity, and repair the gut barrier. Although this product has been proven safe and effective in clinical practice, uncertainty remains regarding its use to treat digestive system diseases. To date, there have been no reference standards to guide clinical practice and no relevant expert consensus on this product, in China. METHODS: Following a literature search, evidence was graded and classified according to the grading of recommendations assessment, development, and evaluation (GRADE) system and consensus was secured from a panel of 52 experts. RESULTS: An expert consensus has been formed, on the clinical application of live combined Bifidobacterium, Lactobacillus, and Enterococcus in various digestive system diseases, to provide reference for its clinical use. CONCLUSIONS: Bifidobacterium triple viable powder/capsule may offer benefits, by regulating the balance of intestinal microecology. It can be used for the treatment and prevention of various digestive system diseases with good overall safety; further research is needed to confirm its application in other contexts. The recommendations in this consensus will be confirmed or refined in light of future research and clinical practice.

Case report: Fecal microbiota transplantation in refractory ankylosing spondylitis.

Ankylosing spondylitis (AS) is the prototype of a group of systemic inflammatory diseases referred to as spondyloarthritis. Comorbid inflammatory bowel disease and changed gut microbiota in AS have attracted attention to the influence of gut-joint axis and encouraged treating AS by targeting gut microbiota. Here we first reported a patient with refractory AS and comorbid ulcerative colitis (UC) who underwent three fecal microbiota transplantations (FMTs). Inadequate response to conventional treatments including tumor necrosis factor inhibitors impelled FMT as alternative therapy. Notable improvements in AS and UC accompanied with changed fecal microbiota were recorded at 1 week post-FMT1. Further recovery was found after the other two FMTs, and a roughly stable status was maintained in the follow-up period. More studies are needed to validate the effectiveness of FMT in AS and its mechanisms.

Efficacy of endoscopic anterior fundoplication with a novel ultrasonic surgical endostapler for gastroesophageal reflux disease: Six-month results from a multicenter prospective trial.

Background and Objectives: Endoscopic therapy is an option for the treatment of refractory gastroesophageal reflux disease (GERD). We aimed to evaluate the efficacy and safety of transoral incisionless fundoplication with the Medigus ultrasonic surgical endostapler (MUSE™) for refractory GERD. Materials and Methods: Patients with 2 years of documented GERD symptoms and at least 6 months of proton-pump inhibitors (PPIs) therapy were enrolled in four medical centers from March 2017 to March 2019. The GERD health-related quality of life (HRQL) score, GERD questionnaire score, total acid exposure on esophageal pH probe monitoring, the gastroesophageal flap valve (GEFV), esophageal manometry, and PPIs dosage were compared between the pre- and post-MUSE procedure. All of the side effects were recorded. Results: A reduction of at least 50% in the GERD-HRQL score was observed in 77.8% (42/54) patients. Most patients 74.1% (40/54) discontinued PPIs and 11.1% (6/54) reported a ≥50% dose reduction. The percentage of patients who had normalized acid exposure time after the procedure was 46.9% (23/49). The existence of hiatal hernia at baseline was negatively correlated with the curative effect. Mild pain was common and resolved within 48 h postprocedure. Serious complications were pneumoperitoneum (one case), mediastinal emphysema combined with pleural effusion (two cases). Conclusions: Endoscopic anterior fundoplication with MUSE was an effective treatment for refractory GERD, but still needs refinement and improvement in safety aspect. Esophageal hiatal hernia may affect the efficacy of MUSE. (www.chictr.org.cn, ChiCTR2000034350).

Gastrointestinal microbiome and cholelithiasis: Current status and perspectives.

Cholelithiasis is a common digestive disease affecting 10% to 15% of adults. It imposes significant global health and financial burdens. However, the pathogenesis of cholelithiasis involves several factors and is incompletely elucidated. In addition to genetic predisposition and hepatic hypersecretion, the pathogenesis of cholelithiasis might involve the gastrointestinal (GI) microbiome, consisting of microorganisms and their metabolites. High-throughput sequencing studies have elucidated the role of bile, gallstones, and the fecal microbiome in cholelithiasis, associating microbiota dysbiosis with gallstone formation. The GI microbiome may drive cholelithogenesis by regulating bile acid metabolism and related signaling pathways. This review examines the literature implicating the GI microbiome in cholelithiasis, specifically gallbladder stones, choledocholithiasis, and asymptomatic gallstones. We also discuss alterations of the GI microbiome and its influence on cholelithogenesis.