Functional microbiomics reveals branched-chain amino acids depletion for alleviation of insulin resistance by berberine

Increased circulating branched-chain amino acids(BCAAs)have been involved in the pathogenesis of obesity and insulin resistance.However,evidence relating berberine(BBR),gut microbiota,BCAAs,and insulin resis⁃tance is limited.Here,we showed that BBR could effectively rectify steatohepatitis and glucose intolerance in high-fat diet(HFD)-fed mice.BBR reorganized gut microbiota populations under both the normal chow diet(NCD)and HFD.Particu⁃larly,BBR noticeably decreased the relative abundance of BCAA-producing bacteria,including order Clostridiales;fami⁃lies Streptococcaceae,Clostridiaceae,and Prevotellaceae;and genera Streptococcus and Prevotella.Compared with the HFD group,predictive metagenomics indicated a reduction in the proportion of gut microbiota genes involved in BCAA biosynthesis but the enrichment genes for BCAA degradation and transport by BBR treatment.Accordingly,the elevated serum BCAAs of HFD group were significantly decreased by BBR.Furthermore,the Western blotting results implied that BBR could promote the BCAA catabolism in the liver and epididymal white adipose tissues of HFD-fed mice by acti⁃vation of the multienzyme branched-chain α-ketoacid dehydrogenase complex,whereas by inhibition of the phosphoryla⁃tion state of BCKDHA(E1α subunit)and branched-chain α-ketoacid dehydrogenase kinase.The ex vivo assay further confirmed that BBR could increase BCAA catabolism in both AML12 hepatocytes and 3T3-L1 adipocytes.Finally,data from healthy subjects and diabetics confirmed that BBR could improve glycemic control and modulate circulating BCAAs.Besides,functional microbiomics integrated high-throughput microbial genomics,metabolomics and molecular biotechnology has also been successfully applied to reveal the anti-obesity mechanism of hydroxysafflor yellow A.

Pharmacomicrobiomics： a novel route towards personalized medicine？

Inter-individual heterogeneity in drug response is a serious problem that affects the patient＇s wellbeing and poses enormous clinical and financial burdens on a societal level. Pharmacogenomics has been at the forefront of research into the impact of individual genetic background on drug response variability or drug toxicity, and recently the gut microbiome, which has also been called the second genome, has been recog- nized as an important player in this respect. Moreover, the microbiome is a very attractive target for improving drug efficacy and safety due to the opportunities to manipulate its composition. Pharmacomicrobiomics is an emerging field that investigates the interplay of microbiome variation and drugs response and disposi- tion （absorption, distribution, metabolism and excretion）. In this review, we provide a historical overview and examine current state-of-the-art knowledge on the complex interactions between gut microbiome, host and drugs. We argue that combining pharmacogenomics and pharmacomicrobiomics will provide an important foundation for making major advances in personalized medicine.

Microbiomics and Plant Health:An Interdisciplinary and International Workshop on the Plant Microbiome

The microbiome refers to the collective genomes of all resident microorganisms of a particular organism,environment,or ecosystem.Plant surfaces and interior parts are populated by myriads of bacteria,fungi,and microbes from other kingdoms, which can have considerable effects on plant growth,disease resistance,abiotic stress tolerance,and nutrient uptake.

Gut microbial regulation of innate and adaptive immunity after traumatic brain injury

Acute care management of traumatic brain injury is focused on the prevention and reduction of secondary insults such as hypotension,hypoxia,intracranial hypertension,and detrimental inflammation.However,the imperative to balance multiple clinical concerns simultaneously often results in therapeutic strategies targeted to address one clinical concern causing unintended effects in other remote organ systems.Recently the bidirectional communication between the gastrointestinal tract and the brain has been shown to influence both the central nervous system and gastrointestinal tract homeostasis in health and disease.A critical component of this axis is the microorganisms of the gut known as the gut microbiome.Changes in gut microbial populations in the setting of central nervous system disease,including traumatic brain injury,have been reported in both humans and experimental animal models and can be further disrupted by off-target effects of patient care.In this review article,we will explore the important role gut microbial populations play in regulating brain-resident and peripheral immune cell responses after traumatic brain injury.We will discuss the role of bacterial metabolites in gut microbial regulation of neuroinflammation and their potential as an avenue for therapeutic intervention in the setting of traumatic brain injury.

Unraveling the gut-brain axis:the impact of steroid hormones and nutrition on Parkinson's disease

This comprehensive review explores the intricate relationship between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the context of the gut-brain axis.The gut-brain axis plays a pivotal role in neurodegenerative diseases like Parkinson's disease,encompassing diverse components such as the gut microbiota,immune system,metabolism,and neural pathways.The gut microbiome,profoundly influenced by dietary factors,emerges as a key player.Nutrition during the first 1000 days of life shapes the gut microbiota composition,influencing immune responses and impacting both child development and adult health.High-fat,high-sugar diets can disrupt this delicate balance,contributing to inflammation and immune dysfunction.Exploring nutritional strategies,the Mediterranean diet's anti-inflammatory and antioxidant properties show promise in reducing Parkinson's disease risk.Microbiome-targeted dietary approaches and the ketogenic diet hold the potential in improving brain disorders.Beyond nutrition,emerging research uncovers potential interactions between steroid hormones,nutrition,and Parkinson's disease.Progesterone,with its anti-inflammatory properties and presence in the nervous system,offers a novel option for Parkinson's disease therapy.Its ability to enhance neuroprotection within the enteric nervous system presents exciting prospects.The review addresses the hypothesis thatα-synuclein aggregates originate from the gut and may enter the brain via the vagus nerve.Gastrointestinal symptoms preceding motor symptoms support this hypothesis.Dysfunctional gut-brain signaling during gut dysbiosis contributes to inflammation and neurotransmitter imbalances,emphasizing the potential of microbiota-based interventions.In summary,this review uncovers the complex web of interactions between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the gut-brain axis framework.Understanding these connections not only offers novel therapeutic insights but also illuminates the origins of neurodegenerative diseases such as Parkinson's disease.

Microbiome changes in esophageal cancer:implications for pathogenesis and prognosis

Esophageal cancer(EC)is an aggressive malignancy with a poor prognosis.Various factors,including dietary habits,and antacid and antibiotic use,have been shown to influence the esophageal microbiome.Conversely,enrichment and diversity of the esophageal microbiome can also impact its function.Recent studies have revealed prevalent changes in the esophageal microbiome among patients with EC,thus suggesting the potential contribution of the esophageal microbiome to EC development.Additionally,distinct microbiome compositions have been observed in patients with different responses to radiotherapy and chemotherapy,indicating the role of the esophageal microbiome in modulating treatment outcomes.In this review,we have examined previous studies on the esophageal microbiome in healthy individuals and patients with EC or other esophageal diseases,with a focus on identifying microbial communities associated with EC pathogenesis and prognosis.Understanding the role of the microbiome in EC may aid in early detection and optimized treatment strategies,ultimately leading to better outcomes for patients.

Magnesium-L-threonate treats Alzheimer's disease by modulating the microbiota-gut-brain axis

Disturbances in the microbiota-gut-brain axis may contribute to the development of Alzheimer's disease. Magnesium-L-threonate has recently been found to have protective effects on learning and memory in aged and Alzheimer's disease model mice. However, the effects of magnesium-L-threonate on the gut microbiota in Alzheimer's disease remain unknown. Previously, we reported that magnesium-L-threonate treatment improved cognition and reduced oxidative stress and inflammation in a double-transgenic line of Alzheimer's disease model mice expressing the amyloid-β precursor protein and mutant human presenilin 1(APP/PS1). Here, we performed 16S r RNA amplicon sequencing and liquid chromatography-mass spectrometry to analyze changes in the microbiome and serum metabolome following magnesium-Lthreonate exposure in a similar mouse model. Magnesium-L-threonate modulated the abundance of three genera in the gut microbiota, decreasing Allobaculum and increasing Bifidobacterium and Turicibacter. We also found that differential metabolites in the magnesiumL-threonate-regulated serum were enriched in various pathways associated with neurodegenerative diseases. The western blotting detection on intestinal tight junction proteins(zona occludens 1, occludin, and claudin-5) showed that magnesium-L-threonate repaired the intestinal barrier dysfunction of APP/PS1 mice. These findings suggest that magnesium-L-threonate may reduce the clinical manifestations of Alzheimer's disease through the microbiota-gut-brain axis in model mice, providing an experimental basis for the clinical treatment of Alzheimer's disease.

Multi-omics analysis reveals the molecular regulatory network underlying the prevention of Lactiplantibacillus plantarum against LPS-induced salpingitis in laying hens

Background Salpingitis is one of the common diseases in laying hen production, which greatly decreases the economic outcome of laying hen farming. Lactiplantibacillus plantarum was effective in preventing local or systemic inflammation, however rare studies were reported on its prevention against salpingitis. This study aimed to investigate the preventive molecular regulatory network of microencapsulated Lactiplantibacillus plantarum(MLP) against salpingitis through multi-omics analysis, including microbiome, transcriptome and metabolome analyses.Results The results revealed that supplementation of MLP in diet significantly alleviated the inflammation and atrophy of uterus caused by lipopolysaccharide(LPS) in hens(P < 0.05). The concentrations of plasma IL-2 and IL-10 in hens of MLP-LPS group were higher than those in hens of LPS-stimulation group(CN-LPS group)(P < 0.05). The expression levels of TLR2, MYD88, NF-κB, COX2, and TNF-α were significantly decreased in the hens fed diet supplemented with MLP and suffered with LPS stimulation(MLP-LPS group) compared with those in the hens of CN-LPS group(P < 0.05). Differentially expressed genes(DEGs) induced by MLP were involved in inflammation, reproduction, and calcium ion transport. At the genus level, the MLP supplementation significantly increased the abundance of Phascolarctobacterium, whereas decreased the abundance of Candidatus_Saccharimonas in LPS challenged hens(P < 0.05). The metabolites altered by dietary supplementation with MLP were mainly involved in galactose, uronic acid, histidine, pyruvate and primary bile acid metabolism. Dietary supplementation with MLP inversely regulates LPSinduced differential metabolites such as Lyso PA(24:0/0:0)(P < 0.05).Conclusions In summary, dietary supplementation with microencapsulated Lactiplantibacillus plantarum prevented salpingitis by modulating the abundances of Candidatus_Saccharimonas, Phascolarctobacterium, Ruminococcus_torques_group and Eubacterium_hallii_group while downregulating the levels of plasma metabolites, p-tolyl sulfate, o-cresol and N-acetylhistamine and upregulating S-lactoylglutathione, simultaneously increasing the expressions of CPNE4, CNTN3 and ACAN genes in the uterus, and ultimately inhibiting oviducal inflammation.

Rethinking neurodegenerative diseases:neurometabolic concept linking lipid oxidation to diseases in the central nervous system

Currently,there is a lack of effective medicines capable of halting or reve rsing the progression of neurodegenerative disorde rs,including amyotrophic lateral sclerosis,Parkinson s disease,multiple sclerosis,or Alzheimer s disease.Given the unmet medical need,it is necessary to reevaluate the existing para digms of how to to rget these diseases.When considering neurodegenerative diseases from a systemic neurometabolic perspective,it becomes possible to explain the shared pathological features.This innovative approach presented in this paper draws upon exte nsive research conducted by the authors and researchers worldwide.In this review,we highlight the importance of metabolic mitochondrial dysfunction in the context of neurodegenerative diseases.We provide an overview of the risk factors associated with developing neurodegenerative disorders,including genetic,epigenetic,and environmental fa ctors.Additionally,we examine pathological mechanisms implicated in these diseases such as oxidative stress,accumulation of misfolded proteins,inflammation,demyelination,death of neurons,insulin resistance,dysbiosis,and neurotransmitter disturbances.Finally,we outline a proposal for the restoration of mitochondrial metabolism,a crucial aspect that may hold the key to facilitating curative therapeutic interventions for neurodegenerative disorders in forthcoming advancements.

New therapy for metabolic syndrome:Gut microbiome supplementation

The gut microbiota is important in the development and progression of metabolic illnesses such type 2 diabetes,cardiovascular disease(CVD),and obesity.This diverse community of microorganisms controls a variety of physiological functions,including metabolism,inflammation,and immune response.Understanding these interactions has resulted in novel therapeutic options,including microbiome supplementation.The gut microbiome is extremely susceptible to dietary changes,which can alter its makeup and function,influencing metabolite synthesis that affects host health.Certain metabolites,such as butyrate and propionate,have been proven to protect against metabolic illnesses,whereas trimethylamine has been linked to CVD.Prebiotics,probiotics,synbiotics,and postbiotics are being investigated by researchers as ways to change the gut microbiome and boost metabolic health.Despite advances in therapy and lifestyle adjustments,the prevalence of metabolic syndrome is increasing,emphasizing the need for new medicines.

Hidden army within:Harnessing the microbiome to improve cancer treatment outcomes

The gut microbiome has emerged as a critical player in cancer pathogenesis and treatment response.Dysbiosis,an imbalance in the gut microbial community,impacts tumor initiation,progression,and therapy outcomes.Specific bacterial species have been associated with either promoting or inhibiting tumor growth,offering potential targets for therapeutic intervention.The gut microbiome in-fluences the efficacy and toxicity of conventional treatments and cutting-edge immunotherapies,highlighting its potential as a therapeutic target in cancer care.However,translating microbiome research into clinical practice requires addres-sing challenges such as standardizing methodologies,validating microbial bio-markers,and ensuring ethical considerations.Here,we provide a comprehensive overview of the gut microbiome's role in cancer highlighting the need for on-going research,collaboration,and innovation to harness its full potential for im-proving patient outcomes in oncology.The current editorial aims to explore these insights and emphasizes the need for standardized methodologies,validation of microbial biomarkers,and interdisciplinary collaboration to translate microbiome research into clinical applications.Furthermore,it underscores ethical consider-ations and regulatory challenges surrounding the use of microbiome-based the-rapies.Together,this article advocates for ongoing research,collaboration,and innovation to realize the full potential of microbiome-guided oncology in impro-ving patient care and outcomes.

Metabolic syndrome’s new therapy:Supplement the gut microbiome

This letter to the editor discusses the publication on gut microbiome supple-mentation as therapy for metabolic syndrome.Gut microbiome dysbiosis disrupts intestinal bacterial homeostasis and is related to chronic inflammation,insulin resistance,cardiovascular diseases,type 2 diabetes mellitus,and obesity.Previous research has found that increasing the abundance of beneficial microbiota in the gut modulates metabolic syndrome by reducing chronic inflammation and insulin resistance.Prebiotics,probiotics,synbiotics,and postbiotics are often used as supplements to increase the number of beneficial microbes and thus the produc-tion of short-chain fatty acids,which have positive effects on the gut microbiome and metabolic syndrome.In this review article,the author summarizes the available supplements to increase the abundance of beneficial gut microbiota and reduce the abundance of harmful microbiota in patients with metabolic disorders.Our group is also researching the role of the gut microbiota in chronic liver disease.This article will be of great help to our research.At the end of the letter,the mechanism of the gut microbiota in chronic liver disease is discussed.

Biodiversity metrics on ecological networks: Demonstrated with animal gastrointestinal microbiomes

Biodiversity has become a terminology familiar to virtually every citizen in modern societies.It is said that ecology studies the economy of nature,and economy studies the ecology of humans;then measuring biodiversity should be similar with measuring national wealth.Indeed,there have been many parallels between ecology and economics,actually beyond analogies.For example,arguably the second most widely used biodiversity metric,Simpson(1949)’s diversity index,is a function of familiar Gini-index in economics.One of the biggest challenges has been the high“diversity”of diversity indexes due to their excessive“speciation”-there are so many indexes,similar to each country’s sovereign currency-leaving confused diversity practitioners in dilemma.In 1973,Hill introduced the concept of“numbers equivalent”,which is based on Renyi entropy and originated in economics,but possibly due to his abstruse interpretation of the concept,his message was not widely received by ecologists until nearly four decades later.What Hill suggested was similar to link the US dollar to gold at the rate of$35 per ounce under the Bretton Woods system.The Hill numbers now are considered most appropriate biodiversity metrics system,unifying Shannon,Simpson and other diversity indexes.Here,we approach to another paradigmatic shift-measuring biodiversity on ecological networks-demonstrated with animal gastrointestinal microbiomes representing four major invertebrate classes and all six vertebrate classes.The network diversity can reveal the diversity of species interactions,which is a necessary step for understanding the spatial and temporal structures and dynamics of biodiversity across environmental gradients.

肠上皮细胞Axin1缺失可调节肠道微生态预防结肠炎

Intestinal homeostasis is maintained by specialized host cells and the gut microbiota.Wnt/β-catenin signaling is essential for gastrointestinal development and homeostasis,and its dysregulation has been implicated in inflammation and colorectal cancer.Axin1 negatively regulates activated Wnt/β-catenin signaling,but little is known regarding its role in regulating host–microbial interactions in health and disease.Here,we aim to demonstrate that intestinal Axin1 determines gut homeostasis and host response to inflammation.Axin1 expression was analyzed in human inflammatory bowel disease datasets.To explore the effects and mechanism of intestinal Axin1 in regulating intestinal homeostasis and colitis,we generated new mouse models with Axin1 conditional knockout in intestinal epithelial cell(IEC;Axin1^(ΔIEC))and Paneth cell(PC;Axin1^(ΔPC))to compare with control(Axin1^(LoxP);LoxP:locus of X-over,P1)mice.We found increased Axin1 expression in the colonic epithelium of human inflammatory bowel disease(IBD).Axin1^(ΔIEC) mice exhibited altered goblet cell spatial distribution,PC morphology,reduced lysozyme expression,and enriched Akkermansia muciniphila(A.muciniphila).The absence of intestinal epithelial and PC Axin1 decreased susceptibility to dextran sulfate sodium(DSS)-induced colitis in vivo.Axin1^(ΔIEC) and Axin1^(ΔPC)mice became more susceptible to DSS-colitis after cohousing with control mice.Treatment with A.muciniphila reduced DSS-colitis severity.Antibiotic treatment did not change the IEC proliferation in the Axin1Loxp mice.However,the intestinal proliferative cells in Axin1^(ΔIEC)mice with antibiotic treatment were reduced compared with those in Axin1^(ΔIEC) mice without treatment.These data suggest non-colitogenic effects driven by the gut microbiome.In conclusion,we found that the loss of intestinal Axin1 protects against colitis,likely driven by epithelial Axin1 and Axin1-associated A.muciniphila.Our study demonstrates a novel role of Axin1 in mediating intestinal homeostasis and the microbiota.Further mechanistic studies using specific Axin1 mutations elucidating how Axin1 modulates the microbiome and host inflammatory response will provide new therapeutic strategies for human IBD.

Interactions between maternal parity and feed additives drive the composition of pig gut microbiomes in the post‑weaning period

Background Nursery pigs undergo stressors in the post-weaning period that result in production and welfare chal-lenges.These challenges disproportionately impact the offspring of primiparous sows compared to those of mul-tiparous counterparts.Little is known regarding potential interactions between parity and feed additives in the post-weaning period and their effects on nursery pig microbiomes.Therefore,the objective of this study was to investigate the effects of maternal parity on sow and offspring microbiomes and the influence of sow parity on pig fecal microbi-ome and performance in response to a prebiotic post-weaning.At weaning,piglets were allotted into three treat-ment groups:a standard nursery diet including pharmacological doses of Zn and Cu(Con),a group fed a commercial prebiotic only(Preb)based on an Aspergillus oryzae fermentation extract,and a group fed the same prebiotic plus Zn and Cu(Preb+ZnCu).Results Although there were no differences in vaginal microbiome composition between primiparous and mul-tiparous sows,fecal microbiome composition was different(R^(2)=0.02,P=0.03).The fecal microbiomes of primiparous offspring displayed significantly higher bacterial diversity compared to multiparous offspring at d 0 and d 21 post-weaning(P<0.01),with differences in community composition observed at d 21(R^(2)=0.03,P=0.04).When analyzing the effects of maternal parity within each treatment,only the Preb diet triggered significant microbiome distinc-tions between primiparous and multiparous offspring(d 21:R^(2)=0.13,P=0.01;d 42:R^(2)=0.19,P=0.001).Composi-tional differences in pig fecal microbiomes between treatments were observed only at d 21(R^(2)=0.12,P=0.001).Pigs in the Con group gained significantly more weight throughout the nursery period when compared to those in the Preb+ZnCu group.Conclusions Nursery pig gut microbiome composition was influenced by supplementation with an Aspergillus oryzae fermentation extract,with varying effects on performance when combined with pharmacological levels of Zn and Cu or for offspring of different maternal parity groups.These results indicate that the development of nursery pig gut microbiomes is shaped by maternal parity and potential interactions with the effects of dietary feed additives.

Evaluation of ruminal methane and ammonia formation and microbiota composition as affected by supplements based on mixtures of tannins and essential oils using Rusitec

Background Dietary supplements based on tannin extracts or essential oil compounds(EOC)have been repeatedly reported as a promising feeding strategy to reduce the environmental impact of ruminant husbandry.A previous batch culture screening of various supplements identified selected mixtures with an enhanced potential to mitigate ruminal methane and ammonia formation.Among these,Q-2(named after quebracho extract and EOC blend 2,composed of carvacrol,thymol,and eugenol)and C-10(chestnut extract and EOC blend 10,consisting of oregano and thyme essential oils and limonene)have been investigated in detail in the present study with the semi-continuous rumen simulation technique(Rusitec)in three independent runs.For this purpose,Q-2 and C-10,dosed according to the previous study,were compared with a non-supplemented diet(negative control,NC)and with one supplemented with the commercial EOC-based Agolin^(R) Ruminant(positive control,PC).Results From d 5 to 10 of fermentation incubation liquid was collected and analysed for pH,ammonia,protozoa count,and gas composition.Feed residues were collected for the determination of ruminal degradability.On d 10,samples of incubation liquid were also characterised for bacterial,archaeal and fungal communities by high-throughput sequencing of 16S rRNA and 26S ribosomal large subunit gene amplicons.Regardless of the duration of the fermentation period,Q-2 and C-10 were similarly efficient as PC in mitigating either ammonia(-37%by Q-2,-34%by PC)or methane formation(-12%by C-10,-12%by PC).The PC was also responsible for lower feed degradability and bacterial and fungal richness,whereas Q-2 and C-10 effects,particularly on microbiome diversities,were limited compared to NC.Conclusions All additives showed the potential to mitigate methane or ammonia formation,or both,in vitro over a period of 10 d.However,several differences occurred between PC and Q-2/C-10,indicating different mechanisms of action.The pronounced defaunation caused by PC and its suggested consequences apparently determined at least part of the mitigant effects.Although the depressive effect on NDF degradability caused by Q-2 and C-10 might partially explain their mitigation properties,their mechanisms of action remain mostly to be elucidated.

Comparative analysis of the microbiome of sympatric wintering Bean Geese,Domestic Ducks,humans,and soil at Shengjin Lake of China reveals potential public risk to human health

The gut microbiota of migratory waterbirds is affected by various complex factors,including cross-species transmission,which increases the risk of pathogen spreading among sympatric animals and poses a potential public health risk to humans.In this study,we investigated the microbial communities of wintering Bean Geese(Anser fabalis),Domestic Ducks(A.platyrhynchos domesticus),humans,and soil using high-throughput sequencing of the 16S rRNA gene region in Shengjin Lake,China.In total,6,046,677 clean reads were obtained,representing 41,119 operational taxonomic units(OTUs)across the four groups.The dominant microbial phyla were the Proteobacteria,Firmicutes,Bacteroidota,and Actinobacteriota.The Sorensen similarity index and alpha and beta diversity results showed that the gut microbial communities of Bean Geese and Domestic Ducks were more similar to those of the other pairs.Network analysis revealed that Faecalibacterium prausnitzii,Pseudomonas fragi,and Bradyrhizobium elkanii were hubs of the three major modules.Fourteen common microbiomes were iden-tified in Bean Geese,Domestic Ducks,humans,and soil in Shengjin Lake.A total of 96 potential pathogens were identified among the four groups,with 20 specific potentially pathogenic microbiomes found in the gut of Bean Geese.Some of these pathogens are responsible for significant financial losses in the poultry industry and pose risks to human health.Klebsiella pneumoniae,Morganella morganii,Escherichia coli,and Ralstonia insidiosa are potential core pathogens found in the four groups at Shengjin Lake that can cause diseases in humans and an-imals and facilitate cross-species transmission through various media.Therefore,humans are at risk of con-tracting these pathogens from migratory birds because of their frequent contact with domestic poultry.However,further studies are required to explore the potential pathogenic species and transmission pathways among sympatric wintering Bean Geese,Domestic Ducks,humans,and soil.

Metabolic syndrome and the urinary microbiome of patients undergoing percutaneous nephrolithotomy

Objective:To identify possible stone-promoting microbes,we compared the profiles of microbes grown from stones of patients with and without metabolic syndrome(MetS).The association between MetS and urinary stone disease is well established,but the exact pathophysiologic relationship remains unknown.Recent evidence suggests urinary tract dysbiosis may lead to increased nephrolithiasis risk.Methods:At the time of percutaneous nephrolithotomy,bladder urine and stone fragments were collected from patients with and without MetS.Both sample types were subjected to expanded quantitative urine culture(EQUC)and 16 S ribosomal RNA gene sequencing.Results:Fifty-seven patients included 12 controls(21.1%)and 45 MetS patients(78.9%).Both cohorts were similar with respect to demographics and non-MetS comorbidities.No controls had uric acid stone composition.By EQUC,bacteria were detected more frequently in MetS stones(42.2%)compared to controls(8.3%)(p=0.041).Bacteria also were more abundant in stones of MetS patients compared to controls.To validate our EQUC results,we performed 16 S ribosomal RNA gene sequencing.In 12/16(75.0%)sequence-positive stones,EQUC reliably isolated at least one species of the sequenced genera.Bacteria were detected in both“infectious”and“non-infectious”stone compositions.Conclusion:Bacteria are more common and more abundant in MetS stones than control stones.Our findings support a role for bacteria in urinary stone disease for patients with MetS regardless of stone composition.

Dynamic gut microbiome-metabolome in cationic bovine serum albumin induced experimental immune-complex glomerulonephritis and effect of losartan and mycophenolate mofetil on microbiota modulation

Dynamic changes in gut dysbiosis and metabolomic dysregulation are associated with immune-complex glomerulonephritis(ICGN).However,an in-depth study on this topic is currently lacking.Herein,we report an ICGN model to address this gap.ICGN was induced via the intravenous injection of cationized bovine serum albumin(c-BSA)into Sprague-Dawley(SD)rats for two weeks,after which mycophenolate mofetil(MMF)and losartan were administered orally.Two and six weeks after ICGN establishment,fecal samples were collected and 16S ribosomal DNA(rDNA)sequencing and untargeted metabolomic were conducted.Fecal microbiota transplantation(FMT)was conducted to determine whether gut normali-zation caused by MMF and losartan contributed to their renal protective effects.A gradual decline in microbial diversity and richness was accompanied by a loss of renal function.Approximately 18 genera were found to have significantly different relative abundances between the early and later stages,and Marvinbryantia and Allobaculum were markedly upregulated in both stages.Untargeted metabolomics indicated that the tryptophan metabolism was enhanced in ICGN,characterized by the overproduction of indole and kynurenic acid,while the serotonin pathway was reduced.Administration of losartan and MMF ameliorated microbial dysbiosis and reduced the accumulation of indoxyl conjugates in feces.FMT using feces from animals administered MMF and losartan improved gut dysbiosis by decreasing the Firmicutes/Bacteroidetes(F/B)ratio but did not improve renal function.These findings indicate that ICGN induces serous gut dysbiosis,wherein an altered tryptophan metabolism may contribute to its pro-gression.MMF and losartan significantly reversed the gut microbial and metabolomic dysbiosis,which partially contributed to their renoprotective effects.

Manipulating the Gut Microbiome to Alleviate Steatotic Liver Disease:Current Progress and Challenges

The prevalence of metabolic-dysfunction-associated steatotic liver disease(MASLD)is alarmingly high;it is estimated to affect up to a quarter of the global population,making it the most common liver disorder worldwide.MASLD is characterized by excessive hepatic fat accumulation and is commonly associated with comorbidities such as obesity,dyslipidemia,and insulin resistance;however,it can also manifest in lean individuals.Therefore,it is crucial to develop effective therapies for this complex condition.Currently,there are no approved medications for MASLD treatment,so there is a pressing need to investigate alternative approaches.Extensive research has characterized MASLD as a multifaceted disease,frequently linked to metabolic disorders that stem from dietary habits.Evidence suggests that changes in the gut microbiome play a fundamental role in the development and progression of MASLD from simple steatosis to steatohepatitis and even hepatocellular carcinoma(HCC).In this review,we critically examine the literature on the emerging field of gut-microbiota-based therapies for MASLD and metabolicdysfunction-associated steatohepatitis(MASH),including interventions such as fecal microbiota transplantation(FMT),probiotics,prebiotics,short-chain fatty acids,antibiotics,metabolic pathway targeting,and immune checkpoint kinase blockade.