Systemic lupus erythematosus (SLE) is characterized by dysregulated immune responses. Paeoniflorin (PF), a highly purified monoterpene glycoside derived from Paeonia lactiflora, exhibits immunomodulatory activity, but its mechanisms in SLE remain unclear. This study investigated whether PF ameliorates SLE by modulating the gut microbiota–lipid metabolite axis and restoring Th17/Treg immune balance. Network pharmacology was applied to predict PF-related targets and pathways in SLE. MRL/lpr mice were treated with PF, and disease severity was assessed by clinical manifestations, autoantibody levels, renal function, and histopathology. Intestinal barrier integrity and motility were evaluated in vivo. Th17 and Treg cell populations in intestinal and peripheral immune tissues were analyzed by flow cytometry. Gut microbiota composition was profiled using 16S rRNA gene sequencing, and untargeted LC–MS/MS–based metabolomics of intestinal contents was performed to identify differential metabolites and enriched metabolic pathways. PF treatment significantly alleviated lupus-like manifestations in MRL/lpr mice, including reduced splenomegaly and lymphadenopathy, decreased serum anti-dsDNA, ANA, total IgG, and IL-17 levels, and improved renal function and histopathological injury. PF restored Th17/Treg balance by suppressing IL-17–producing CD4⁺ T cells and promoting Foxp3⁺ Treg cells across intestinal and peripheral immune compartments. PF also improved intestinal barrier integrity and reshaped gut microbial composition by reducing inflammation-associated taxa and enriching beneficial bacteria. Metabolomic analysis demonstrated that PF markedly downregulated glycerophospholipid metabolism, particularly reducing lysophosphatidic acid (LPA) and lysophosphatidylcholine (LPC), which have been reported to promote RORγt activity and Th17 differentiation. Correlation analyses linked microbial alterations with lipid metabolite changes and Th17/Treg-associated immune parameters. Paeoniflorin alleviates SLE by regulating a gut microbiota–lipid metabolite–immune axis, suppressing pro-Th17 lysophospholipid metabolism and restoring Th17/Treg immune homeostasis.

The extreme environmental conditions of a plateau have an important impact on the economic development of the area, including tourism and employment. High-altitude environments, characterized by hypoxia, low atmospheric pressure, and intense ultraviolet radiation, are recognized as key contributors to gastrointestinal injury. These environmental stresses promote oxidative stress, inflammatory responses, and gut microbiota dysbiosis, resulting in intestinal barrier disruption, increased permeability, and immune imbalance, which collectively predispose individuals to gastrointestinal disorders and multi-organ dysfunction. Accumulating evidence suggests that natural bioactive molecules, probiotics, and synbiotics exert protective effects against high-altitude-induced intestinal injury via diverse mechanisms. Accordingly, this review focuses on the key mechanisms of high-altitude hypoxia-induced intestinal injury and discusses the therapeutic potential of intestinal function-enhancing molecules. This work aims to offer a theoretical framework and identify potential intervention targets for the management of gastrointestinal disorders associated with high-altitude exposure.

Honeybees (Apis mellifera), as social insects, exhibit complex social behaviors and cognitive functions. The short lifespan and stable gut microorganisms of honeybees provide certain availability as a rapid and high-flux animal model for aging research. This study explored the effect of D-galactose, a common aging inducer, on honeybees and investigated the associated effects and mechanisms, with particular focus on the potential protective role of sodium butyrate. Experimental cohorts were established as follows: conventional (CV) group, D-galactose-treated (DG) group, and sodium butyrate-treated (SB) group. The CV group was fed sucrose solution; the DG group was fed D-galactose solution; and the SB group was fed D-galactose and sodium butyrate solution. A comprehensive assessment was conducted on day 15 post-treatment, including survival analysis, starvation test, motor, learning and memory ability tests, malondialdehyde test, and Smurf test. Potential mechanisms through the microbiome and metabolome were investigated. Compared to the honeybees from the CV group, those in the DG group showed a shortened lifespan, a weaker energy storage ability, impaired motor, learning, and memory abilities, reduced weight, increased oxidation, and a disrupted gut barrier. These phenotypic changes were associated with microbial dysbiosis characterized by Lactobacillus enrichment and diminished butyrate levels. Notably, sodium butyrate supplementation extended the honeybees' lifespan and improved their learning and memory abilities damaged by D-galactose. Our findings establish honeybees as a valuable model system for aging research and highlight the crucial role of butyrate metabolism in senescence regulation.IMPORTANCEThis study presents a novel approach to investigating aging processes by establishing a D-galactose-induced aging model in honeybees. Our findings demonstrate that butyrate supplementation effectively attenuates D-galactose-induced senescence phenotypes, suggesting its potential as a therapeutic intervention for age-related decline. This research provides a unique model system for aging studies and highlights the significant role of butyrate in modulating senescence progression. The results contribute to our understanding of the molecular mechanisms underlying aging and offer new insights into potential anti-aging strategies.

Introduction:Gut microbial therapy has emerged as a prominent research topic for brain function and disorders. The depletion of Phocaeicola coprocola has been reported in various brain-related conditions, suggesting its possible neuroprotective and cognitive benefits. However, its functional roles and underlying mechanisms remain poorly understood. Methods:We evaluated the effects of P. coprocola on cognitive performance using the honeybee (Apis mellifera) as a novel model for the microbiota-gut-brain axis. Honeybees with a standardized gut microbiota served as the control group, while those supplemented with P. coprocola comprised the treatment group. Olfactory learning and memory were assessed using classical conditioning assays. Gut microbial composition was analyzed using full-length 16S rRNA gene sequencing based on PacBio SMRT technology, and metabolic profiling was conducted using untargeted LC-MS/MS analysis. Results:P. coprocola supplementation significantly improved cognitive performance, with learning success rates of 74.13% in the treatment group versus 50.85% in controls (p = 0.0093). This intervention also led to increased gut diversity (Shannon index, p = 0.0079). Metabolomic analysis revealed substantial alterations in intestinal lipid metabolism, particularly in glycerophospholipid pathways (p = 0.0002). Furthermore, the increase in protective lipid molecules, such as phosphatidylcholine, glycerophosphocholine, and glycerophosphoethanolamine, was strongly correlated with Gilliamella apicola, Bifidobacterium asteroides, and Bombella apis. Discussion:P. coprocola has potential as a probiotic candidate for modulating cognition-related processes via gut microbial and metabolic interactions. Moreover, the honeybee model offers a valuable platform for preclinical investigation of microbiota-gut-brain relationships and probiotic screenin.

BACKGROUND Helicobacter pylori (H. pylori ) infection is a prevalent disease encountered in military internal medicine and recognized as the main cause of dyspepsia, gastritis, and peptic ulcer, which are common diseases in military personnel. Current guidelines in China state all patients with evidence of active infection with H. pylori are offered treatment. However, the prevalence of H. pylori infection and its regional distribution in the military population remain unclear, which hinders effective prevention and treatment strategies. Understanding the prevalence of H. pylori infection in the military population will aid in the development of customized strategies to better manage this infectious disease. AIM To investigate the prevalence of H. pylori infection in the Chinese military population in different geographic areas. METHODS This multicenter, retrospective study included 22421 individuals from five tertiary hospitals located in north, east, southwest, and northwest cities of China. H. pylori infection was identified using the urea breath test, which had been performed between January 2020 and December 2021. RESULTS Of the 22421 military service members, 7416 (33.1%) were urea breath test-positive. The highest prevalence of H. pylori was in the 30-39 years age group for military personnel, with an infection rate of 34.9%. The majority of infected subjects were younger than 40-years-old, accounting for 70.4% of the infected population. The individuals serviced in Lanzhou and Chengdu showed a higher infection prevalence than those in Beijing, Nanjing, and Guangzhou, with prevalence rates of 44.3%, 37.9%, 29.0%, 31.1%, and 32.3%, respectively. CONCLUSION H. pylori infection remains a common infectious disease among military personnel in China and has a relatively high prevalence rate in northwest China.

ABSTRACT:Brain science is the frontier of modern science, and new advances have been made in brain-like designs and brain-computer interfaces to simulate or develop brain functions. However, given that the brain is hermetically sealed within the skull, exploration and deciphering of the brain structure and functions are limited. Growing evidence suggests that the gut is not just a digestive organ. It not only provides essential nutrients and electrolytes for brain neurodevelopment and the maintenance of brain function, but it also transmits external environmental and intestinal wall signals from the intestinal lumen to the central nervous system through multiple pathways to regulate brain activity, function, and structure. A variety of gut-brain interaction pathways have been identified, including neural pathways, neuroimmune signaling, endocrine pathways, and biochemical messengers produced by gut microbes. Gut microbes interact with food and the gut to modulate gut-brain communication. The gut's important role and potential in neurodevelopment, maintenance of normal function, and disease development make it an increasingly important area of research in brain science and neuropsychiatric disorders. The gut's unique role in brain functions and its accessibility for research (compared to direct brain studies) establish it as a critical gate to understanding the mysteries of brain science. Crucially, intestinal nutrients and microbes provide two unique keys to unlock this gate-enabling neural regulation and novel treatments for neuropsychiatric diseases.

ABSTRACT Background The increasing incidence of inflammatory bowel disease (IBD) presents significant medical and societal challenges. A well‐designed IBD database is crucial for both epidemiological studies and clinical management. However, inconsistencies between regional databases hinder cross‐institutional and international research, especially between Eastern and Western societies. Methods We developed a new IBD database, the 301 IBD database, integrating the IBD clinical characteristics from the Penn IBD database (USA) and the latest IBD guidelines and consensus and clinical practices of the Chinese PLA General Hospital (PLAGH). We applied this database to analyze clinical data of IBD inpatients at PLAGH from 2008 to 2023. Results The 301 IBD database contains 490 items in 6 sections including demographic characteristics, personal history, clinical phenotype, disease activity, laboratory tests and examinations, and treatment. Features of the 301 IBD database include inpatient focus, biochemical indicators and opportunistic infection focus, and more about ulcerative colitis (UC)‐associated complications. Single‐center analysis revealed an increasing hospitalization trend, from 2.35% in 2008 to 3.94% in 2023. We found that the clinical characteristics of our UC inpatients are predominantly male (62.5%), extensive lesions (55.1%), low usage of biologics (4.1%), and a high incidence of UC‐CRC (3.0%). The clinical characteristics of CD inpatients included male predominance (68.39%), early onset age (35.43 ± 14.75‐year‐old), and high rate of surgery (25.81%). Conclusion The 301 IBD database, integrating Eastern and Western clinical data, provides a valuable tool for IBD clinical research. Future international, multicenter collaborations are expected to further enhance its utility.

Microbiotherapy has opened new avenues for managing dysbiosis-related diseases. However, many studies did not cover all the necessary reporting items for microbiotherapy making the interpretation of results, safety assessment, technology extension, and even the transparency of legitimacy difficult. This project consisted of 2 phases. First, we proposed an initial preferred reporting items for microbiotherapy (PRIM) checklist and applied it to oncology studies from 2011 to 2023 according to Meta-Analyses guideline. Only 39.3% (n = 64) of these studies (n = 163) met all PRIM checklist items. The culture-based microbiotherapy (CMT) studies had higher score than non-culture-based (NMT) ones (p = 0.018). In the second phase, the expert panel consisting of 22 specialists from eight countries across Asia, Australia, Europe, and North America refined and finalized the PRIM guidelines (named as PRIM 2024) through Delphi consensus. The PRIM 2024 guidelines conclude 10 statements and 18 points on diagnosis, delivery route, source, classification, preparation, dosage, state, concomitant treatment, efficacy, and safety. The panel defined less than 80% of all PRIM points (14 points) as low-quality reports. These guidelines are recommended for reporting on microbiotherapy in clinical studies and reports on compassionate use, including but not limited to fecal microbiota transplantation, phage therapy, probiotics, and synbiotics. These consistent and transparent reporting items can help researchers and practitioners better evaluate, compare, implement research findings in microbiotherapy.

BackgroundAt present, no commercially available endoscopic system is specifically designed for use in the battlefield, disaster relief, or unique environments with biosafety concerns. Therefore, this limitation stems from challenges such as limited portability, reliance on stable power, complex disinfection processes, and the risk of incomplete sterilization. To address these challenges, we developed a novel portable endoscopic system and evaluated its safety and effectiveness in both routine settings and specialized scenarios, including the global pandemic caused by a novel coronavirus, which represents an environment with biosafety concerns.MethodsAfter sample size calculation, 30 patients underwent esophagogastroduodenoscopy (EGD) or colonoscopy using the YunSendo (the experimental group) and Olympus systems (the control group) in a randomized order. Operation time, image quality, operational performance, lesion detection, and safety were assessed. Ten emergency patients with suspected upper gastrointestinal bleeding received bedside treatment using the YunSendo system during the global pandemic caused by a novel coronavirus. Clinical outcomes in emergency endoscopic treatment were assessed.ResultsNo significant differences were observed between the YunSendo and Olympus groups in terms of image quality, lesion detection, and overall procedural performance. YunSendo facilitated biopsy and colonic polyp removal; no adverse endoscopy events were reported. YunSendo successfully executed diagnostic and therapeutic procedures in emergencies, with no observed mortality at 1, 7, or 30 d, no rebleeding at 1 or 30 d, and no cross-infection rates.ConclusionsThe performance of the YunSendo portable endoscopic system was comparable to the Olympus system in terms of key metrics, demonstrating its utility in urgent scenarios. This novel system is particularly promising for medical rescue and military missions and for addressing battlefield and biosafety concerns.

Background The gut microbiota is closely associated with autism spectrum disorders (ASD), but the specific microorganism involved is not well understood. Bacteroides fragilis has been implicated in ASD in rodent models, though the evidence is inconclusive. B. fragilis exhibits remarkable genetic diversity and can be categorized into enterotoxigenic B. fragilis (ETBF) or non-toxigenic B. fragilis (NTBF). We aimed to investigate the potential role of B. fragilis in the ASD population. Methods Fecal samples were collected from 70 individuals with ASD, 45 individuals with Tic disorder (TD) as disease controls, and 64 healthy controls (HC) for PCR analysis to identify B. fragilis and ETBF. In five ASD children who were ETBF (+) and received fecal microbiota transplantation (FMT) treatment, we compared the ETBF copy number by quantitative PCR before and after FMT. Results There was no significant difference in the detection of B. fragilis between the ASD, TD, and HC groups, whereas ETBF was higher in ASD than in TD (21.43% vs. 6.67%, P = 0.0335) and HC (21.43% vs. 7.81%, P = 0.0272) (IDDF2024-ABS-0172 Figure 1. Stacked histogram of B. fragilis and subtype in ASD TD and HC children). Among five ASD children who tested positive for ETBF and received FMT treatment, 80% (4/5) showed a clinical response, a 4.5-point decrease in the CARS-2 score. Four cases had a reduction in their CARS-2 score by 5.5-6.5 and a decrease in ETBF copy number by over 90%. One non-responding case had a 2-point decrease in their CARS-2 score and a 49.88% decrease in ETBF copy number (IDDF2024-ABS-0172 Figure 2. Cars 2 scores and fecal ETBF copy number was reduced after FMT treatment in five ASD children). Conclusions The detection rate of ETBF was higher in ASD than in TD and HC children. FMT efficacy was correlated with ETBF, which may be a predictor of FMT efficacy for ASD. ETBF is a potential intestinal pathogen and biomarker for diagnostic and therapeutic targets for ASD.

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.

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.

Background Tryptophan (Trp) is an essential amino acid in the human body with a complex metabolic pathway. Recently, tryptophan metabolites have been proposed to influence intestinal ecological balance and intestinal inflammation by acting on intestinal immune cells to sustain intestinal immunological homeostasis via the aromatic hydrocarbon receptor (AHR). Nonetheless, the mechanism of action of these metabolites on intestinal epithelial cells is yet to be determined. Methods An intestinal epithelial cell inflammation model was established by applying lipopolysaccharide (LPS) for 24 hours on the Caco2 cell line derived from human colon carcinoma and the NCM460 cell line generated from normal human colon epithelial cells. Subsequently, L-tryptophan and its three metabolites (tryptamine, indole-3-carboxaldehyde, and L-kynurenine) were treated independently, and CH223191 (an aromatic hydrocarbon receptor antagonist) was added to explore the mechanism of action. Using an enzyme-linked immunosorbent assay (ELISA), we assessed the concentrations of TNF-α, IL-1β, IL-6 and IL-10 in the cell supernatant and the mRNA and protein expression of major regulator of intestinal permeability (Occludin, Claudin-1, ZO-1), Ahr and NF-κB were detected by real-time quantitative transcription polymerase chain reaction (RT-qPCR) and western blot. Results Compared with the inflammation model group, the addition of tryptophan, tryptamine, indole-3-carboxaldehyde, and L-kynurenine at a concentration of 10μmol/L resulted in a significant decrease in TNF-α, IL-1β, and IL-6 levels (P<0.05) and an elevated level in IL-10 (P<0.05), as well as a marked up-regulation (P<0.05) of the expressions of Occludin, Claudin-1, ZO-1 and Ahr protein and mRNA expressions (P<0.05) and a widespread down-regulation of NF-KB mRNA expression (P<0.05) in comparison to the experimental control group. Even so, the impact of the aforementioned medications was reversed upon the addition of CH223191, and all data was returned. Conclusions L-Tryptophan and its three metabolites (tryptamine, indole-3-carboxaldehyde, and L-kynurenine) upregulate aryl hydrocarbon receptors and inhibit the NF-KB signaling pathway, alleviate intestinal epithelial cell inflammation, and enhance intestinal epithelial cell tight junctions.

Background Helicobacter pylori (H. pylori) infection is a prevalent disease and is recognized as the main cause of many diseases including dyspepsia, gastritis, and gastric cancer. The prevalence of H. pylori infection and its regional distribution in Chinese civilians has recently changed. Understanding the prevalence of H. pylori infection and its regional variation will aid in the development of customized strategies to better manage this infectious disease. This investigation aimed to learn the prevalence of H. pylori infection in civilians from five tertiary hospitals located in the Northwest, Southeast, North, South, and Southwest cities of China. Methods This investigation was a multicenter retrospective cross-sectional study. A total of 71,645 participants who underwent urea breath test (UBT) between January 2020 and December 2021 at five tertiary hospitals in Beijing, Nanjing, Guangzhou, Lanzhou, and Chengdu were included. Basic demographic information and UBT data were collected. H. pylori infection was diagnosed using UBT. Results Of 71,645 individuals, 24,289 (33.9%) were UBT-positive. The highest prevalence of H. pylori was in the 30-39 years group, with infection rates of 35.6% (6980/19611), followed by the 18-29 years group (34.6%, 4360/12586), 40-49 years group (34.6%, 4627/13383), 50-59 years group (33.8%, 4714/13965), 70-79 years group (30.0%, 1248/4157), and 60-69 years group (29.7%, 2360/7943). The individuals in Lanzhou and Chengdu showed a higher infection prevalence than those in Beijing, Nanjing, and Guangzhou, with prevalence rates of 44.8% (6768/15094), 36.7% (1679/4574), 28.5% (7333/25697), 31.9% (7502/23519), and 36.5% (1007/2761), respectively. There were significant differences in infection rates among different regions (P<0.001). Conclusions H. pylori is still a common infection among civilians in China and has a relatively higher infection rate in Northwest China.