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.

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.

Gut microbiome and orthopaedic health:Bridging the divide between digestion and bone integrity

The gut microbiome,a complex ecosystem of microorganisms in the digestive tract,has emerged as a critical factor in human health,influencing metabolic,immune,and neurological functions.This review explores the connection between the gut microbiome and orthopedic health,examining how gut microbes impact bone density,joint integrity,and skeletal health.It highlights mechanisms linking gut dysbiosis to inflammation in conditions such as rheumatoid arthritis and osteoarthritis,suggesting microbiome modulation as a potential therapeutic strategy.Key findings include the microbiome’s role in bone metabolism through hormone regulation and production of short-chain fatty acids,crucial for mineral absorption.The review also considers the effects of diet,probiotics,and fecal microbiota transplantation on gut microbiome composition and their implications for orthopedic health.While promising,challenges in translating microbiome research into clinical practice persist,necessitating further exploration and ethical consideration of microbiome-based therapies.This interdisciplinary research aims to link digestive health with musculoskeletal integrity,offering new insights into the prevention and management of bone and joint diseases.

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.

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.

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.

The correlation between gut microbiome and atrial fibrillation: pathophysiology and therapeutic perspectives

Regulation of gut microbiota and its impact on human health is the theme of intensive research.The incidence and prevalence of atrial fibrillation(AF)are continuously escalating as the global population ages and chronic disease survival rates increase;however,the mechanisms are not entirely clarified.It is gaining awareness that alterations in the assembly,structure,and dynamics of gut microbiota are intimately engaged in the AF progression.Owing to advancements in next-generation sequencing technologies and computational strategies,researchers can explore novel linkages with the genomes,transcriptomes,proteomes,and metabolomes through parallel meta-omics approaches,rendering a panoramic view of the culture-independent microbial investigation.In this review,we summarized the evidence for a bidirectional correlation between AF and the gut microbiome.Furthermore,we proposed the concept of“gut-immune-heart”axis and addressed the direct and indirect causal roots between the gut microbiome and AF.The intricate relationship was unveiled to generate innovative microbiota-based preventive and therapeutic interventions,which shed light on a definite direction for future experiments.

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.

Supplementation of Lycium barbarum residue increases the growth rate of Tan sheep by enhancing their feed intake and regulating their rumen microbiome and metabolome

Lycium barbarum residue(LBR),a by-product of L.barbarum processing,is packed with bioactive components and can be potentially utilized as a feed additive in animal husbandry.However,the fundamental understanding of its effectiveness on livestock animals is still lacking,particularly in ruminants.To explore the effects of LBR on the growth performance,rumen fermentation parameters,ruminal microbes and metabolites of Tan sheep,sixteen fattening rams(aged 4 mon)were fed a basal diet(CON,n=8)or a basal diet supplemented with 5%LBR(LBR,n=8).The experiment lasted for 70 d,with 10 d adaptation period and 60 d treatment period.The results showed that the LBR enhanced the average daily feed intake,average daily gain(P<0.05),and ruminal total volatile fatty acids(P<0.01)while decreasing ammonia-nitrogen concentration and rumen pH value(P<0.05).Additionally,the LBR improved the relative abundances of Prevotella,Succiniclasticum,Ruminococcus,Coprococcus,Selenomonas,and Butyrivibrio(P<0.05)and reduced the relative abundances of Oscillospira and Succinivibrio(P<0.05).The LBR altered the ruminal metabolome(P<0.01)by increasing the abundances of ruminal metabolites involved in amino acids(e.g.,L-proline,L-phenylalanine,L-lysine,and L-tyrosine),pyrimidine metabolism(e.g.,uridine,uracil,and thymidine),and microbial protein synthesis(e.g.,xanthine and hypoxanthine).In conclusion,LBR had positive effects on the growth rate of Tan sheep as well as on rumen fermentation parameters,rumen microbiome and rumen metabolome.

Core and variable antimicrobial resistance genes in the gut microbiomes of Chinese and European pigs

Monitoring the prevalence of antimicrobial resistance genes(ARGs)is vital for addressing the global crisis of antibiotic-resistant bacterial infections.Despite its importance,the characterization of ARGs and microbiome structures,as well as the identification of indicators for routine ARG monitoring in pig farms,are still lacking,particularly concerning variations in antimicrobial exposure in different countries or regions.Here,metagenomics and random forest machine learning were used to elucidate the ARG profiles,microbiome structures,and ARG contamination indicators in pig manure under different antimicrobial pressures between China and Europe.Results showed that Chinese pigs exposed to high-level antimicrobials exhibited higher total and plasmid-mediated ARG abundances compared to those in European pigs(P<0.05).ANT(6)-Ib,APH(3')-IIIa,and tet(40)were identified as shared core ARGs between the two pig populations.Furthermore,the core ARGs identified in pig populations were correlated with those found in human populations within the same geographical regions.Lactobacillus and Prevotella were identified as the dominant genera in the core microbiomes of Chinese and European pigs,respectively.Forty ARG markers and 43 biomarkers were able to differentiate between the Chinese and European pig manure samples with accuracies of 100%and 98.7%,respectively.Indicators for assessing ARG contamination in Chinese and European pigs also achieved high accuracy(r=0.72-0.88).Escherichia flexneri in both Chinese and European pig populations carried between 21 and 37 ARGs.The results of this study emphasize the importance of global collaboration in reducing antimicrobial resistance risk and provide validated indicators for evaluating the risk of ARG contamination in pig farms.

Decoding the fruit microbiome:A climate smart strategy to manage postharvest decays

There is an urgent necessity to shift our diets toward those rich in fruits and vegetables and at reduce postharvest losses of perishables.Approximately 20%-50%of fruits and vegetables are lost due to poor postharvest handling and pathogen infections in developing countries while it was estimated as 5%-35%in developed countries. Fresh fruits have evolved with a plethora of microorganisms having important roles in maintaining fruit health. However, little information is available on the dynamics, structure, and functional capacities of underpinning fruit microbiomes. The present review discussed environmental conditions favoring fruit-harbored antagonists and their different modes of action for suppressing postharvest pathogens in fruits. It also provides information on omics technologies such as next-generation sequencing (NGS),metaproteomics, metatranscriptomic, and metabolomics studies to characterize fruit microbiomes. With the advent of NGS and meta-omics technologies, microbiome research could bring remarkable development and understanding in succeeding biological treatments. In addition, they may provide us with a fundamental understanding of microclimate requirements for fruit microbiome establishment and microbiome shifts during post-harvest storage, which would be advantageous in developing composite biocontrol treatments for post-harvest decay management.

Exploring the modulatory role of bovine lactoferrin on the microbiome and the immune response in healthy and Shiga toxin‑producing E.coli challenged weaned piglets

Background Post-weaned piglets suffer from F18+Escherichia coli(E.coli)infections resulting in post-weaning diar-rhoea or oedema disease.Frequently used management strategies,including colistin and zinc oxide,have contrib-uted to the emergence and spread of antimicrobial resistance.Novel antimicrobials capable of directly interacting with pathogens and modulating the host immune responses are being investigated.Lactoferrin has shown promising results against porcine enterotoxigenic E.coli strains,both in vitro and in vivo.Results We investigated the influence of bovine lactoferrin(bLF)on the microbiome of healthy and infected weaned piglets.Additionally,we assessed whether bLF influenced the immune responses upon Shiga toxin-producing E.coli(STEC)infection.Therefore,2 in vivo trials were conducted:a microbiome trial and a challenge infection trial,using an F18+STEC strain.BLF did not affect theα-andβ-diversity.However,bLF groups showed a higher relative abundance(RA)for the Actinobacteria phylum and the Bifidobacterium genus in the ileal mucosa.When analysing the immune response upon infection,the STEC group exhibited a significant increase in F18-specific IgG serum levels,whereas this response was absent in the bLF group.Conclusion Taken together,the oral administration of bLF did not have a notable impact on theα-andβ-diversity of the gut microbiome in weaned piglets.Nevertheless,it did increase the RA of the Actinobacteria phylum and Bifi-dobacterium genus,which have previously been shown to play an important role in maintaining gut homeostasis.Furthermore,bLF administration during STEC infection resulted in the absence of F18-specific serum IgG responses.

Integrated chromosomal instability and tumor microbiome re define d prognosis-related subtypes of pancreatic cancer

Background:Pancreatic cancer is a common malignancy with poor prognosis and limited treatment.Here we aimed to investigate the role of host chromosomal instability(CIN)and tumor microbiome in the prognosis of pancreatic cancer patients.Methods:One hundred formalin-fixed paraffin-embedded(FFPE)pancreatic cancer samples were collected.DNA extracted from FFPE samples were analyzed by low-coverage whole-genome sequencing(WGS)via a customized bioinformatics workflow named ultrasensitive chromosomal aneuploidy detector.Results:Samples were tested according to the procedure of ultrasensitive chromosomal aneuploidy detector(UCAD).We excluded 2 samples with failed quality control,1 patient lost to follow-up and 6 dead in the perioperative period.The final 91 patients were admitted for the following analyses.Thirteen(14.3%)patients with higher CIN score had worse overall survival(OS)than those with lower CIN score.The top 20 microbes in pancreatic cancer samples included 15 species of bacteria and 5 species of viruses.Patients with high human herpesvirus(HHV)-7 and HHV-5 DNA reads exhibited worse OS.Furthermore,we classified 91 patients into 3 subtypes.Patients with higher CIN score(n=13)had the worst prognosis(median OS 6.9 mon);patients with lower CIN score but with HHV-7/5 DNA load(n=24)had worse prognosis(median OS 10.6 mon);while patients with lower CIN score and HHV-7/5 DNA negative(n=54)had the best prognosis(median OS 21.1 mon).Conclusions:High CIN and HHV-7/5 DNA load were associated with worse survival of pancreatic cancer.The novel molecular subtypes of pancreatic cancer based on CIN and microbiome had prognostic value.

Lactobacillus from fermented bamboo shoots prevents inflammation in DSS-induced colitis mice via modulating gut microbiome and serum metabolites

Fermented bamboo shoots(FBS)is a region-specific food widely consumed in Southwestern China,with Lactobacillus as the predominant fermenting bacteria.However,the probiotic potential of Lactobacillus derived from FBS reminds largely unexplored,especially for diseases with a low prevalence in areas consuming FBS,namely,inflammatory bowel disease.In this study,Lactiplantibacillus pentosus YQ001 and Lentilactobacillus senioris YQ005 were screening by in vitro probiotic tests to further investigate the probioticlike bioactivity in dextran sulfate sodium(DSS)-induced ulcerative colitis(UC)mouse.They exhibited more positive probiotic effects than Lactobacillus rhamnosus GG in preventing intestinal inflammatory response.The results revealed that both strains improved the abundance of deficient intestinal microbiota in UC mice,including Muribaculaceae and Akkermansia.In the serum metabolome,they modulated the DSS-disturbed levels of metabolites,with significant increment of cinnamic acid.Meanwhile,they reduced the expression levels of interleukin-1β(IL-1β),interleukin-6(IL-6)inflammatory factors and increased zonula occludens-1(ZO-1),Occludin,and cathelicidin-related antimicrobial peptide(CRAMP)in the colon.Consequently,these results demonstrated that Lactobacillus spp.isolates derived from FBS showed promising probiotic activity based on the gut microbiome homeostasis modulation,anti-inflammation and intestinal barrier protection in UC mice.

Establishment of a chronic biliary disease mouse model with cholecystoduodenal anastomosis for intestinal microbiome preservation

BACKGROUND Chronic biliary disease,including cholangitis and cholecystitis,is attributed to ascending infection by intestinal bacteria.Development of a mouse model for bile duct inflammation is imperative for the advancement of novel therapeutic approaches.Current models fail to replicate the harmful bacterial influx to the biliary tract observed in humans and spread of inflammation to the liver.Therefore,we aimed to establish an animal model of biliary disease that faithfully replicates the mechanisms of human diseases.AIM To establish a cholecystoduodenal anastomosis model capable of mimicking the mechanisms of ascending infection and inflammation observed in human biliary diseases.METHODS We established a mouse biliary disease model by directly connecting the gallbladder and duodenum,enabling ascending infection into the biliary tract without traversing the sphincter of Oddi.RESULTS In the cholecystoduodenal anastomosis mouse model,we observed impaired epithelial structure,wall thickening,and macrophage recruitment in the gallbladder.Despite the absence of postoperative antibiotics,we detected no changes in serum proinflammatory cytokine levels,indicating no systemic inflammation.Moreover,patency between the gallbladder and duodenum was confirmed via common bile duct ligation.Injection of patient-derived pathogenic bacteria into bile duct-ligated mice led to ascending infection,which significantly increased proinflammatory cytokine mRNA expression in the liver,duodenum,and ileum.These results indicate that our mouse model exhibited a direct connection between the gallbladder and duodenum,leading to ascending infection and closely mimicking the clinical features of biliary diseases observed in humans.CONCLUSION The cholecystoduodenal anastomosis mouse model is an effective chronic biliary disease model with significant relevance in the development of microbiome-based therapies for the prevention and treatment of biliary disease.

Antihypertensive effects of whey protein hydrolysate involve reshaping the gut microbiome in spontaneously hypertension rats

Novel angiotensin-converting enzyme(ACE)inhibitory peptides were identified from whey protein hydrolysates(WPH)in vitro in our previous study and the antihypertensive abilities of WPH in vivo were further investigated in the current study.Results indicated that WPH significantly inhibited the development of high blood pressure and tissue injuries caused by hypertension.WPH inhibited ACE activity(20.81%,P<0.01),and reduced renin concentration(P<0.05),thereby reducing systolic blood pressure(SBP)(12.63%,P<0.05)in spontaneously hypertensive rats.The increased Akkermansia,Bacteroides,and Lactobacillus abundance promoted high short chain fatty acid content in feces after WPH intervention.These changes jointly contributed to low blood pressure.The heart weight and cardiomyocyte injuries(hypertrophy and degeneration)were alleviated by WPH.The proteomic results revealed that 19 protein expressions in the heart mainly associated with the wingless/integrated(Wnt)signaling pathway and Apelin signaling pathway were altered after WPH supplementation.Notably,WPH alleviated serum oxidative stress,indicated by the decreased malondialdehyde content(P<0.01),enhanced total antioxidant capacity(P<0.01)and superoxide dismutase activity(P<0.01).The current study suggests that WPH exhibit promising antihypertensive abilities in vivo and could be a potential alternative for antihypertensive dietary supplements.