Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have rev...Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have revealed that gut microbiota can communicate bidirectionally with the brain through the gut microbiota–brain axis.This axis indicates that gut microbiota is closely related to the development and prognosis of intracerebral hemorrhage and its associated secondary white matter injury.The NACHT,LRR,and pyrin domain-containing protein 3(NLRP3)inflammasome plays a crucial role in this context.This review summarizes the dysbiosis of gut microbiota following intracerebral hemorrhage and explores the mechanisms by which this imbalance may promote the activation of the NLRP3 inflammasome.These mechanisms include metabolic pathways(involving short-chain fatty acids,lipopolysaccharides,lactic acid,bile acids,trimethylamine-N-oxide,and tryptophan),neural pathways(such as the vagus nerve and sympathetic nerve),and immune pathways(involving microglia and T cells).We then discuss the relationship between the activated NLRP3 inflammasome and secondary white matter injury after intracerebral hemorrhage.The activation of the NLRP3 inflammasome can exacerbate secondary white matter injury by disrupting the blood–brain barrier,inducing neuroinflammation,and interfering with nerve regeneration.Finally,we outline potential treatment strategies for intracerebral hemorrhage and its secondary white matter injury.Our review highlights the critical role of the gut microbiota–brain axis and the NLRP3 inflammasome in white matter injury following intracerebral hemorrhage,paving the way for exploring potential therapeutic approaches.展开更多
Helicobacter pylori(H.pylori)infection remains a pivotal driver of chronic gastritis,peptic ulcer,gastric mucosa-associated lymphoid tissue lymphoma and gastric cancer,yet its eradication is increasingly frustrated by...Helicobacter pylori(H.pylori)infection remains a pivotal driver of chronic gastritis,peptic ulcer,gastric mucosa-associated lymphoid tissue lymphoma and gastric cancer,yet its eradication is increasingly frustrated by climbing antibiotic resistance and intolerable side-effects of standard triple or quadruple therapies.In recent years,fecal microbiota transplantation(FMT),a strategy that reconstructs the gut ecosystem by introducing a healthy donor microbiome,has emerged as a novel adjunct or alternative.By competitively excluding H.pylori,reinforcing mucosal barrier integrity,modulating host immunity and secreting bacteriocins,FMT can raise eradication rates,relieve dyspeptic symptoms and lower recurrence.This review synthesizes up-to-date pre-clinical,pilot and controlled clinical data,dissects underlying mechanisms,compares delivery routes,donor screening protocols and safety profiles,and discusses regulatory,ethical and standardization hurdles that must be overcome before large-scale clinical application.展开更多
Acute pancreatitis(AP)is sudden inflammation of the pancreas,which can lead to multiple organ dysfunction in severe cases.Hypertriglyceridemia(HTG)is the third most common cause.In recent years,HTG-induced AP(HTG-AP)h...Acute pancreatitis(AP)is sudden inflammation of the pancreas,which can lead to multiple organ dysfunction in severe cases.Hypertriglyceridemia(HTG)is the third most common cause.In recent years,HTG-induced AP(HTG-AP)has garnered increasing attention.Compared to AP caused by other causes,HTG-AP often has a more subtle onset but is more likely to progress to a severe,critical illness that poses a serious threat to a patient’s life and health.Research suggests a potential connection between the gut microbiota and AP,which could be mediated by bacterial metabolites,immune cells,and inflammatory factors.This is supported by observations of microbial imbalance and higher intestinal permeability in patients with AP.In addition,studies have shown that HTG-induced changes in gut microbiota can worsen AP by negatively impacting the host metabolism,immune response,and function of the intestinal barrier.In this review,we summarize recent clinical and animal studies on the role and mechanism of gut microbiota in the severity of AP aggravated by HTG.The application prospects of the newly proposed microbial-host-isozyme concept are summarized,focusing on its potential for the precision diagnosis and treatment of HTG-AP through gut microbiota regulation.展开更多
Acute kidney injury(AKI)is a critical condition with limited effective therapies.Akkermansia muciniphila(A.muciniphila)is a probiotic with multiple beneficial effects,including the regulation of epithelial cell tight ...Acute kidney injury(AKI)is a critical condition with limited effective therapies.Akkermansia muciniphila(A.muciniphila)is a probiotic with multiple beneficial effects,including the regulation of epithelial cell tight junctions.Since renal pathophysiology is associated with gut barrier integrity,we hypothesized that A.muciniphila may have preventive effects on AKI.We established a lipopolysaccharide(LPS)-induced AKI mouse model to evaluate the effects of A.muciniphila.Our findings showed that pretreatment with A.muciniphila significantly attenuated kidney injury,as evidenced by reduced serum creatinine and urea nitrogen levels,alongside decreased tubular necrosis and apoptosis.A.muciniphila preserved intestinal barrier integrity and induced marked shifts in gut microbial ecology and the metabolome.A.muciniphila notably induced an increase in the relative abundance of the phylum Proteobacteria while decreasing in that of the phylum Bacteroidetes.At the genus level,Prevotella,Faecalibaculum,Moraxella,and Lactobacillus were more abundant in A.muciniphilapretreated mice.Metabolomic analysis revealed that A.muciniphila altered the gut metabolome,with changes involving pathways such as tyrosine metabolism,alanine/aspartate/glutamate homeostasis,cancer-related carbon flux,and GABAergic synaptic signaling.In conclusion,our findings indicate that A.muciniphila exerts renoprotective effects by modulating the gut-kidney axis,thereby establishing a foundation for future studies to explore the connection between gut microbiota and AKI.展开更多
Indicaxanthin is a betalain that is abundant in Opuntia ficus-indica orange fruit and has antioxidative and anti-inflammatory effects. Nevertheless, very little is known about the neuroprotective potential of indicaxa...Indicaxanthin is a betalain that is abundant in Opuntia ficus-indica orange fruit and has antioxidative and anti-inflammatory effects. Nevertheless, very little is known about the neuroprotective potential of indicaxanthin. This study investigated the impact of indicaxanthin on neuronal damage and gut microbiota dysbiosis induced by a high-fat diet in mice. The mice were divided into three groups according to different diets: the negative control group was fed a standard diet;the high-fat diet group was fed a high-fat diet;and the high-fat diet + indicaxanthin group was fed a high-fat diet and received indicaxanthin orally(0.86 mg/kg per day) for 4 weeks. Brain apoptosis, redox status, inflammation, and the gut microbiota composition were compared among the different animal groups. The results demonstrated that indicaxanthin treatment reduced neuronal apoptosis by downregulating the expression of proapoptotic genes and increasing the expression of antiapoptotic genes. Indicaxanthin also markedly decreased the expression of neuroinflammatory proteins and genes and inhibited high-fat diet–induced neuronal oxidative stress by reducing reactive oxygen and nitrogen species, malondialdehyde, and nitric oxide levels. In addition, indicaxanthin treatment improved the microflora composition by increasing the abundance of healthy bacterial genera, known as producers of short-chain fatty acids(Lachnospiraceae, Alloprovetella, and Lactobacillus), and by reducing bacteria related to unhealthy profiles(Blautia, Faecalibaculum, Romboutsia and Bilophila). In conclusion, indicaxanthin has a positive effect on high-fat diet–induced neuronal damage and on the gut microbiota composition in obese mice.展开更多
BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese med...BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese medicines.It is known for its suppression of inflammation and mitigation of oxidative stress.Its therapeutic efficacy and mechanistic underpinnings in UC remain uncharacterized.AIM To investigate the therapeutic potential and mechanisms of CE in UC.METHODS The anti-inflammatory activity and intestinal barrier-repairing effects of CE were assessed in a dextran sulfate sodium-induced murine colitis model.Network pharmacology was employed to predict potential targets and pathways.Then molecular docking and dynamics simulations were utilized to confirm a stable interaction between CE and the toll-like receptor 4(TLR4)/myeloid differentiation factor 2(MD2)complex.The anti-inflammatory mechanisms were further verified using in vitro assays.Additionally,the gut microbiota composition was analyzed via 16S rRNA gene sequencing.RESULTS CE significantly alleviated colitis symptoms,mitigated histopathological damage,and suppressed inflammation.Moreover,CE restored intestinal barrier integrity by enhancing mucus secretion and upregulating tight junction proteins(zonula occludens 1,occludin,claudin-1).Mechanistically,CE stably bound to MD2,inhibiting lipopolysaccharide-induced TLR4 signaling in RAW264.7 cells.This led to suppression of the downstream mitogen-activated protein kinase and nuclear factor kappa B signaling pathways,downregulating the expression of tumor necrosis factor-alpha,interleukin-1β,and interleukin-6.Gut microbiota analysis revealed that CE reversed dextran sulfate sodium-induced dysbiosis with significant enrichment of butyrogenic Christensenella minuta.CONCLUSION CE acted on MD2 to suppress proinflammatory cascades,promoting mucosal barrier reconstitution and microbiota remodeling and supporting its therapeutic use in UC.展开更多
Clostridioides difficile(C.difficile)is one of the major causes of nosocomial infections.Pregnant women,who are generally considered at low risk for C.difficile infection(CDI),have attracted attention because of an in...Clostridioides difficile(C.difficile)is one of the major causes of nosocomial infections.Pregnant women,who are generally considered at low risk for C.difficile infection(CDI),have attracted attention because of an increasing number of reports.Oral vancomycin,the only first-line treatment for pregnant women infected with C.difficile,has been associated with increasing strain resistance,leading to decreased efficacy.Fecal microbiota transplantation(FMT)is recommended for severe,fulminant,and recurrent CDI;however,it is generally avoided in pregnant women because of safety concerns.We report a case of a pregnant woman with a primary ribotype 027 CDI who experienced a successful outcome with washed microbiota transplantation(WMT),an improved form of FMT,via enema.The specific strain of ribotype 027 is related to severe outcomes but has not previously been reported in pregnant women.The follow-up lasted for two years,during which the patient's diarrhea was fully alleviated without recurrence.The baby showed normal growth and development,and no adverse events were recorded for either.This case provides evidence for the efficacy and safety of WMT in pregnant women infected with C.difficile,indicating that WMT via enema may be a viable therapeutic strategy for this population for treating CDI.展开更多
Colorectal cancer(CRC)is ranked as the third most common tumor globally,representing approximately 10%of all cancer cases,and is the second primary cause of cancer-associated mortality.Existing therapeutic approaches ...Colorectal cancer(CRC)is ranked as the third most common tumor globally,representing approximately 10%of all cancer cases,and is the second primary cause of cancer-associated mortality.Existing therapeutic approaches demonstrate limited efficacy against CRC,partially due to the immunosuppressive tumor microenvironment(TME).In recent years,substantial evidence indicates that dysbiosis of the gut microbiota and its metabolic products is closely associated with the initiation,progression,and prognostic outcomes of CRC.In this minireview,we systematically elaborate on how these microbes and their metabolites directly impair intestinal epithelial integrity,activate cancer-associated fibroblasts,remodel tumor vasculature,and critically,sculpt an immunosuppressive landscape by modulating T cells,dendritic cells,and tumor-associated macrophages.We highlight the translational potential of targeting the gut microbiota,including fecal microbiota transplantation,probiotics,and engineered microbial systems,to reprogram the TME and overcome resistance to immunotherapy and chemotherapy.A deeper understanding of the microbiota-TME axis is essential for developing novel diagnostic and therapeutic paradigms for CRC.展开更多
The gut microbiota:The human body is colonized by a diverse and complex microbial community–including bacteria,viruses,archaea,and unicellular eukaryotes–that plays a central role in human wellbeing.Indeed,microbiot...The gut microbiota:The human body is colonized by a diverse and complex microbial community–including bacteria,viruses,archaea,and unicellular eukaryotes–that plays a central role in human wellbeing.Indeed,microbiota is crucial for several functions,including host metabolism,physiology,maintenance of the intestinal epithelial integrity,nutrition,and immune function,earning it the designation of a“vital organ”(Guinane and Cotter,2013).展开更多
We read with great interest the study by Zhang et al on Yiyi Fuzi Baijiang powder(YFB),which exemplifies the power of modern methods to validate traditional Chinese medicine(TCM).The key insight is that YFB doesn’t m...We read with great interest the study by Zhang et al on Yiyi Fuzi Baijiang powder(YFB),which exemplifies the power of modern methods to validate traditional Chinese medicine(TCM).The key insight is that YFB doesn’t merely alter“good”or“bad”bacteria but restores the gut microbiota’s holistic equilibrium.This is powerfully shown by its paradoxical reduction of anaerobic probiotics like Bifidobacterium,rectifying the diseased,hypoxic environment,causing their aberrant overgrowth.This challenges the conventional probiotic paradigm and underscores a core TCM principle:Herbal formulas treat disease by restoring the body’s overall functional balance.Future research should focus on the interplay between herbal components,intestinal oxygen,and microbial metabolites to further unravel this sophisticated dialogue.展开更多
Extensive evidence demonstrates that a healthy and well-balanced gut microbiota profoundly influences host nutrient absorption,immunity,and metabolism.Unlike mammals,early microbiota colonization in commercial poultry...Extensive evidence demonstrates that a healthy and well-balanced gut microbiota profoundly influences host nutrient absorption,immunity,and metabolism.Unlike mammals,early microbiota colonization in commercial poultry largely depends on the environment as chicks hatch in incubators under a relatively sterile environment(egg and incubator sterilization)without maternal-offspring interaction.The early gut microbiota remains unsaturated,providing a critical window for modulation and influencing the subsequent microbiota succession,which may have long-term health outcomes.Microbiota transplantation(MT)involves transferring the microbiota from a donor to a recipient to modulate the recipient’s microbiota toward a desired state.Successfully applied in human medicine,MT is also gaining attention in poultry production to modulate intestinal health.This review comprehensively explores factors affecting MT,its mechanisms,and its potential applications in chickens,providing insights for further research and commercial use.展开更多
Colorectal cancer(CRC)is increasingly recognized as a multifactorial disease influenced by hereditary,environmental,and microbial factors.This article explores recent insights into the role of gut microbiota dysbiosis...Colorectal cancer(CRC)is increasingly recognized as a multifactorial disease influenced by hereditary,environmental,and microbial factors.This article explores recent insights into the role of gut microbiota dysbiosis in CRC patho-genesis and progression.Key differences in microbial composition,characterized by enrichment of pro-carcinogenic species such as Fusobacterium nucleatum and Bacteroides fragilis and depletion of beneficial commensals like Faecalibacterium prausnitzii,have been identified alongside changes in microbial metabolites such as short-chain fatty acids and secondary bile acids.We discuss immune system modulation by the microbiota,formation of bacterial biofilms,and the activation of host pathways such as the urea cycle during tumorigenesis.Special attention is given to therapeutic innovations,including microbiota-informed precision modelling,synthetic biology-based engineered probiotics,and evolving altern-atives to fecal microbiota transplantation.These integrative strategies represent promising tools in the era of personalized oncology for CRC.展开更多
Alzheimer’s disease not only affects the brain,but also induces metabolic dysfunction in peripheral organs and alters the gut microbiota.The aim of this study was to investigate systemic changes that occur in Alzhei...Alzheimer’s disease not only affects the brain,but also induces metabolic dysfunction in peripheral organs and alters the gut microbiota.The aim of this study was to investigate systemic changes that occur in Alzheimer’s disease,in particular the association between changes in peripheral organ metabolism,changes in gut microbial composition,and Alzheimer’s disease development.To do this,we analyzed peripheral organ metabolism and the gut microbiota in amyloid precursor protein-presenilin 1(APP/PS1)transgenic and control mice at 3,6,9,and 12 months of age.Twelve-month-old APP/PS1 mice exhibited cognitive impairment,Alzheimer’s disease-related brain changes,distinctive metabolic disturbances in peripheral organs and fecal samples(as detected by untargeted metabolomics sequencing),and substantial changes in gut microbial composition compared with younger APP/PS1 mice.Notably,a strong correlation emerged between the gut microbiota and kidney metabolism in APP/PS1 mice.These findings suggest that alterations in peripheral organ metabolism and the gut microbiota are closely related to Alzheimer’s disease development,indicating potential new directions for therapeutic strategies.展开更多
This letter addresses the recently published manuscript by Darnindro et al,which investigates the diversity and composition of colonic mucosal microbiota in Indonesian patients with and without colorectal cancer(CRC)....This letter addresses the recently published manuscript by Darnindro et al,which investigates the diversity and composition of colonic mucosal microbiota in Indonesian patients with and without colorectal cancer(CRC).Although the analysis revealed no statistically significant differences in alpha diversity between the CRC and non-CRC groups,the authors identified notable distinctions in the composition and diversity of colonic mucosal microbiota among patients with CRC compared to those without.At the genus level,a statistically significant difference in microbiota composition was documented between the two cohorts.Specifically,the genera Bacteroides,Campylobacter,Peptostreptococcus,and Parvimonas were found to be elevated in individuals with CRC,while Faecalibacterium,Haemophilus,and Phocaeicola were more prevalent in the non-CRC group.展开更多
Depression poses a considerable threat to global health,underscoring the critical need for safe treatments.Because of its homology of medicine and food,Gardeniae Fructus is widely used in clinical and everyday life co...Depression poses a considerable threat to global health,underscoring the critical need for safe treatments.Because of its homology of medicine and food,Gardeniae Fructus is widely used in clinical and everyday life contexts.Gardeniae Fructus oil(OGF)is a waste byproduct of the food industry with promising recycling potential.While previous research has demonstrated the antidepressant effects of OGF,the precise mechanism remains unclear.To fill this gap in the literature,this paper elucidates the composition and potential antidepressant mechanism of OGF.According to the results,OGF is mainly composed of fatty acids and unsaponifiable matter.OGF could effectively attenuate depression-like behaviors in mice with chronic unpredictable mild stress by modulating the microbiota-gut-brain axis.Mechanisms include improving gut dysbiosis,regulating short-chain fatty acids,protecting the intestinal barrier function,reducing hippocampal damage,and alleviating neuroinflammation by inhibiting the activation of the TLR4/NF-κB/NLRP3 pathway.Fecal microbiota transplantation experiments confirmed the involvement of the gut microbiota in the modulation of depression-like behavior by OGF.This study establishes the antidepressant effects of OGF as well as the underlying mechanism,demonstrating its potential as a novel dietary intervention for depression treatment.展开更多
Inflammatory bowel disease,particularly Crohn's disease(CD),has been linked to modifications in mesenteric adipose tissue(MAT)and the phenomenon known as"creeping fat"(CrF).The presence of CrF is believe...Inflammatory bowel disease,particularly Crohn's disease(CD),has been linked to modifications in mesenteric adipose tissue(MAT)and the phenomenon known as"creeping fat"(CrF).The presence of CrF is believed to serve as a predictor for early clinical recurrence following surgical intervention in patients with CD.Notably,the incorporation of the mesentery during ileocolic resection for CD has been correlated with a decrease in surgical recurrence,indicating the significant role of MAT in the pathogenesis of CD.While numerous studies have indicated that dysbiosis of the gut microbiota is a critical factor in the development of CD,the functional implications of translocated microbiota within the MAT of CD patients remain ambiguous.This manuscript commentary discusses a recent basic research conducted by Wu et al.In their study,intestinal bacteria from individuals were transplanted into CD model mice,revealing that fecal microbiota trans-plantation(FMT)from healthy donors alleviated CD symptoms,whereas FMT from CD patients exacerbated these symptoms.Importantly,FMT was found to affect intestinal permeability,barrier function,and the levels of proinflammatory factors and adipokines.Collectively,these findings suggest that targeting MAT and CrF may hold therapeutic potential for patients with CD.However,the study did not evaluate the composition of the intestinal microbiota of the donors or the subsequent alterations in the gut microbiota.Overall,the gut microbiota plays a crucial role in the histopathology of CD,and thus,targeting MAT and CrF may represent a promising avenue for treatment in this patient population.展开更多
Microorganisms such as bacteria,fungi,viruses,parasites living in the human intestine constitute the human intestinal microbiota.Dysbiosis refers to composi-tional and quantitative changes that negatively affect healt...Microorganisms such as bacteria,fungi,viruses,parasites living in the human intestine constitute the human intestinal microbiota.Dysbiosis refers to composi-tional and quantitative changes that negatively affect healthy gut microbiota.In recent years,with the demonstration that many diseases are associated with dysbiosis,treatment strategies targeting the correction of dysbiosis in the treat-ment of these diseases have begun to be investigated.Faecal microbiota trans-plantation(FMT)is the process of transferring faeces from a healthy donor to another recipient in order to restore the gut microbiota and provide a therapeutic benefit.FMT studies have gained popularity after probiotic,prebiotic,symbiotic studies in the treatment of dysbiosis and related diseases.FMT has emerged as a potential new therapy in the treatment of allergic diseases as it is associated with the maintenance of intestinal microbiota and immunological balance(T helper 1/T helper 2 cells)and thus suppression of allergic responses.In this article,the definition,application,safety and use of FMT in allergic diseases will be discussed with current data.展开更多
Dyslipidemia,a complex disorder characterized by systemic lipid profile abnormalities,affects more than half of adults globally and constitutes a major modifiable risk factor for atherosclerotic cardiovascular disease...Dyslipidemia,a complex disorder characterized by systemic lipid profile abnormalities,affects more than half of adults globally and constitutes a major modifiable risk factor for atherosclerotic cardiovascular disease.Mounting evidence has established the gut microbiota(GM)as a pivotal metabolic modulator that is correlated with atherogenic lipid profiles through dietary biotransformation,immunometabolic regulation,and bioactive metabolite signaling.However,the host-microbe interactions that drive dyslipidemia pathogenesis involve complex gene-environment crosstalk spanning epigenetic modifications to circadian entrainment.Mechanistically,GM perturbations disrupt lipid homeostasis via lipopolysaccharide-triggered hepatic very low-density lipoprotein overproduction,short-chain fatty acid-G protein-coupled receptor 43/41-mediated adipocyte lipolysis,bile acid-farnesoid X receptor/Takeda G proteincoupled receptor 5 axis dysfunction altering cholesterol flux,microbialβ-oxidation intermediates impairing mitochondrial energetics,and host-microbiota noncoding RNA crosstalk regulating lipogenic genes.This comprehensive review systematically examines three critical dimensions,including bidirectional GMlipid axis interactions,molecular cascades bridging microbial ecology to metabolic dysfunction,and translational applications of GM modulation through precision probiotics,structure-specific prebiotics,and a metabolically optimized fecal microbiota transplantation protocol.Notwithstanding these advances,critical gaps persist in establishing causal microbial taxa-pathway relationships and optimal intervention timing.Future directions require longitudinal multi-omic studies,gnotobiotic models for mechanistic validation,and machine learning-driven personalized microbiota profiling.This synthesis provides a framework for developing microbiotacentric strategies targeting dyslipidemia pathophysiology,with implications for precision dyslipidemia management and next-generation cardiovascular disease prevention.展开更多
The gut microbiota plays a pivotal role in the pathogenesis of liver diseases,particularly hepatic encephalopathy(HE),in which dysbiosis contributes to ammonia production,systemic inflammation,and neurocognitive dysfu...The gut microbiota plays a pivotal role in the pathogenesis of liver diseases,particularly hepatic encephalopathy(HE),in which dysbiosis contributes to ammonia production,systemic inflammation,and neurocognitive dysfunction.Emerging evidence suggests that targeting the gut-liver axis through pharmacological and microbiota-based interventions can mitigate liver disease progression and HE severity.This review explored the latest therapeutic strategies aimed at modulating gut microbiota in liver disease,focusing on traditional approaches such as non-absorbable disaccharides(lactulose,lactitol),antibiotics(rifaximin),and probiotics as well as novel interventions,including postbiotics,synbiotics,and fecal microbiota transplantation.Additionally,bile acid modulators,short-chain fatty acid derivatives,and microbiome-targeted small molecules are being investigated for their potential to restore gut-liver homeostasis.We also discussed the implications of gut microbiota modulation in conditions beyond HE,such as metabolic dysfunction-associated steatotic liver disease and cirrhosis.By integrating gut microbiotatargeted therapies into liver disease management,we may develop more effective,personalized approaches to improve patient outcomes and reduce complications.展开更多
The significance of gut microbiota(GM)in human health is being increasingly researched.An imbalance in GM composition,known as dysbiosis,is linked to various and other health issues.In addition,antibiotics are the pri...The significance of gut microbiota(GM)in human health is being increasingly researched.An imbalance in GM composition,known as dysbiosis,is linked to various and other health issues.In addition,antibiotics are the primary and most significant factors leading to major changes in the composition and function of the GM,which may result in colonization by antimicrobial-resistant(AMR)pathogens.Therefore,alternative antibiotic strategies for combating AMR pathogens are urgently needed.This narrative review highlights current knowledge regarding various pertinent strategies for decolonizing bacterial pathogens from GM and emphasizes decolonization therapies’critical role in pediatric surgical disorders.Strategies such as decontamination of the digestive tract utilizing antibiotics,the use of probiotics,and particularly fecal microbiota transplantation have introduced new options for clinical treatment.These treatments show the potential to restore GM balance and have demonstrated advantages for intestinal disorders related to pediatric surgery,including inflammatory bowel disease,neonatal necrotizing enterocolitis,Hirschsprung-associated enterocolitis,and short bowel syndrome.Despite GM therapeutics,recent strategies are still in their developmental phase and exhibit challenges that need further research.Thus,potential future directions for GMtargeted decolonization therapies are under consideration.Innovative alternative strategies to combat AMR though GM modulation in disorders related to pediatric surgery appear to be promising and should continue to be prioritized for further research and development.展开更多
基金supported by the Guangdong Basic and Applied Basic Research Foundation,No.2023A1515030045(to HS)Presidential Foundation of Zhujiang Hospital of Southern Medical University,No.yzjj2022ms4(to HS)。
文摘Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have revealed that gut microbiota can communicate bidirectionally with the brain through the gut microbiota–brain axis.This axis indicates that gut microbiota is closely related to the development and prognosis of intracerebral hemorrhage and its associated secondary white matter injury.The NACHT,LRR,and pyrin domain-containing protein 3(NLRP3)inflammasome plays a crucial role in this context.This review summarizes the dysbiosis of gut microbiota following intracerebral hemorrhage and explores the mechanisms by which this imbalance may promote the activation of the NLRP3 inflammasome.These mechanisms include metabolic pathways(involving short-chain fatty acids,lipopolysaccharides,lactic acid,bile acids,trimethylamine-N-oxide,and tryptophan),neural pathways(such as the vagus nerve and sympathetic nerve),and immune pathways(involving microglia and T cells).We then discuss the relationship between the activated NLRP3 inflammasome and secondary white matter injury after intracerebral hemorrhage.The activation of the NLRP3 inflammasome can exacerbate secondary white matter injury by disrupting the blood–brain barrier,inducing neuroinflammation,and interfering with nerve regeneration.Finally,we outline potential treatment strategies for intracerebral hemorrhage and its secondary white matter injury.Our review highlights the critical role of the gut microbiota–brain axis and the NLRP3 inflammasome in white matter injury following intracerebral hemorrhage,paving the way for exploring potential therapeutic approaches.
基金the 2026 Health Commission Fund of Guizhou Province,China.the freestatistics suite for its technical support.
文摘Helicobacter pylori(H.pylori)infection remains a pivotal driver of chronic gastritis,peptic ulcer,gastric mucosa-associated lymphoid tissue lymphoma and gastric cancer,yet its eradication is increasingly frustrated by climbing antibiotic resistance and intolerable side-effects of standard triple or quadruple therapies.In recent years,fecal microbiota transplantation(FMT),a strategy that reconstructs the gut ecosystem by introducing a healthy donor microbiome,has emerged as a novel adjunct or alternative.By competitively excluding H.pylori,reinforcing mucosal barrier integrity,modulating host immunity and secreting bacteriocins,FMT can raise eradication rates,relieve dyspeptic symptoms and lower recurrence.This review synthesizes up-to-date pre-clinical,pilot and controlled clinical data,dissects underlying mechanisms,compares delivery routes,donor screening protocols and safety profiles,and discusses regulatory,ethical and standardization hurdles that must be overcome before large-scale clinical application.
基金Supported by the Innovation Foundation for Doctor Dissertation of Northwestern Polytechnical University,No.CX2023021.
文摘Acute pancreatitis(AP)is sudden inflammation of the pancreas,which can lead to multiple organ dysfunction in severe cases.Hypertriglyceridemia(HTG)is the third most common cause.In recent years,HTG-induced AP(HTG-AP)has garnered increasing attention.Compared to AP caused by other causes,HTG-AP often has a more subtle onset but is more likely to progress to a severe,critical illness that poses a serious threat to a patient’s life and health.Research suggests a potential connection between the gut microbiota and AP,which could be mediated by bacterial metabolites,immune cells,and inflammatory factors.This is supported by observations of microbial imbalance and higher intestinal permeability in patients with AP.In addition,studies have shown that HTG-induced changes in gut microbiota can worsen AP by negatively impacting the host metabolism,immune response,and function of the intestinal barrier.In this review,we summarize recent clinical and animal studies on the role and mechanism of gut microbiota in the severity of AP aggravated by HTG.The application prospects of the newly proposed microbial-host-isozyme concept are summarized,focusing on its potential for the precision diagnosis and treatment of HTG-AP through gut microbiota regulation.
基金funded by the National Natural Science Foundation of China(Grant No.82470766 to H.M.)the Jiangsu Provincial Medical Key Discipline(Laboratory)Cultivation Unit(Grant No.JSDW202206 to C.X.)the First Affiliated Hospital of Nanjing Medical University Clinical Capacity Enhancement Project(Grant No.JSPH-MC-2022-18 to C.X.).
文摘Acute kidney injury(AKI)is a critical condition with limited effective therapies.Akkermansia muciniphila(A.muciniphila)is a probiotic with multiple beneficial effects,including the regulation of epithelial cell tight junctions.Since renal pathophysiology is associated with gut barrier integrity,we hypothesized that A.muciniphila may have preventive effects on AKI.We established a lipopolysaccharide(LPS)-induced AKI mouse model to evaluate the effects of A.muciniphila.Our findings showed that pretreatment with A.muciniphila significantly attenuated kidney injury,as evidenced by reduced serum creatinine and urea nitrogen levels,alongside decreased tubular necrosis and apoptosis.A.muciniphila preserved intestinal barrier integrity and induced marked shifts in gut microbial ecology and the metabolome.A.muciniphila notably induced an increase in the relative abundance of the phylum Proteobacteria while decreasing in that of the phylum Bacteroidetes.At the genus level,Prevotella,Faecalibaculum,Moraxella,and Lactobacillus were more abundant in A.muciniphilapretreated mice.Metabolomic analysis revealed that A.muciniphila altered the gut metabolome,with changes involving pathways such as tyrosine metabolism,alanine/aspartate/glutamate homeostasis,cancer-related carbon flux,and GABAergic synaptic signaling.In conclusion,our findings indicate that A.muciniphila exerts renoprotective effects by modulating the gut-kidney axis,thereby establishing a foundation for future studies to explore the connection between gut microbiota and AKI.
基金funding from the European Union -NextGenerationEU through the Italian Ministry of University and Research under PRIN PNRR REG D.R.1718-2022– Project number PRJ-1575 INDICA。
文摘Indicaxanthin is a betalain that is abundant in Opuntia ficus-indica orange fruit and has antioxidative and anti-inflammatory effects. Nevertheless, very little is known about the neuroprotective potential of indicaxanthin. This study investigated the impact of indicaxanthin on neuronal damage and gut microbiota dysbiosis induced by a high-fat diet in mice. The mice were divided into three groups according to different diets: the negative control group was fed a standard diet;the high-fat diet group was fed a high-fat diet;and the high-fat diet + indicaxanthin group was fed a high-fat diet and received indicaxanthin orally(0.86 mg/kg per day) for 4 weeks. Brain apoptosis, redox status, inflammation, and the gut microbiota composition were compared among the different animal groups. The results demonstrated that indicaxanthin treatment reduced neuronal apoptosis by downregulating the expression of proapoptotic genes and increasing the expression of antiapoptotic genes. Indicaxanthin also markedly decreased the expression of neuroinflammatory proteins and genes and inhibited high-fat diet–induced neuronal oxidative stress by reducing reactive oxygen and nitrogen species, malondialdehyde, and nitric oxide levels. In addition, indicaxanthin treatment improved the microflora composition by increasing the abundance of healthy bacterial genera, known as producers of short-chain fatty acids(Lachnospiraceae, Alloprovetella, and Lactobacillus), and by reducing bacteria related to unhealthy profiles(Blautia, Faecalibaculum, Romboutsia and Bilophila). In conclusion, indicaxanthin has a positive effect on high-fat diet–induced neuronal damage and on the gut microbiota composition in obese mice.
基金Supported by the Provincial Key Cultivation Laboratory for Digestive Disease Research,No.2021SYS13Shanxi Province’s“Si Ge Yi Pi”Science and Technology Driven Medical Innovation Project,No.2021MX03Shanxi Provincial Basic Research Program,No.202403021222423.
文摘BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese medicines.It is known for its suppression of inflammation and mitigation of oxidative stress.Its therapeutic efficacy and mechanistic underpinnings in UC remain uncharacterized.AIM To investigate the therapeutic potential and mechanisms of CE in UC.METHODS The anti-inflammatory activity and intestinal barrier-repairing effects of CE were assessed in a dextran sulfate sodium-induced murine colitis model.Network pharmacology was employed to predict potential targets and pathways.Then molecular docking and dynamics simulations were utilized to confirm a stable interaction between CE and the toll-like receptor 4(TLR4)/myeloid differentiation factor 2(MD2)complex.The anti-inflammatory mechanisms were further verified using in vitro assays.Additionally,the gut microbiota composition was analyzed via 16S rRNA gene sequencing.RESULTS CE significantly alleviated colitis symptoms,mitigated histopathological damage,and suppressed inflammation.Moreover,CE restored intestinal barrier integrity by enhancing mucus secretion and upregulating tight junction proteins(zonula occludens 1,occludin,claudin-1).Mechanistically,CE stably bound to MD2,inhibiting lipopolysaccharide-induced TLR4 signaling in RAW264.7 cells.This led to suppression of the downstream mitogen-activated protein kinase and nuclear factor kappa B signaling pathways,downregulating the expression of tumor necrosis factor-alpha,interleukin-1β,and interleukin-6.Gut microbiota analysis revealed that CE reversed dextran sulfate sodium-induced dysbiosis with significant enrichment of butyrogenic Christensenella minuta.CONCLUSION CE acted on MD2 to suppress proinflammatory cascades,promoting mucosal barrier reconstitution and microbiota remodeling and supporting its therapeutic use in UC.
基金supported by the Nanjing Medical University Fan Daiming Research Funds for Holistic Integrative Medicine(Grant No.2023-3HIM).
文摘Clostridioides difficile(C.difficile)is one of the major causes of nosocomial infections.Pregnant women,who are generally considered at low risk for C.difficile infection(CDI),have attracted attention because of an increasing number of reports.Oral vancomycin,the only first-line treatment for pregnant women infected with C.difficile,has been associated with increasing strain resistance,leading to decreased efficacy.Fecal microbiota transplantation(FMT)is recommended for severe,fulminant,and recurrent CDI;however,it is generally avoided in pregnant women because of safety concerns.We report a case of a pregnant woman with a primary ribotype 027 CDI who experienced a successful outcome with washed microbiota transplantation(WMT),an improved form of FMT,via enema.The specific strain of ribotype 027 is related to severe outcomes but has not previously been reported in pregnant women.The follow-up lasted for two years,during which the patient's diarrhea was fully alleviated without recurrence.The baby showed normal growth and development,and no adverse events were recorded for either.This case provides evidence for the efficacy and safety of WMT in pregnant women infected with C.difficile,indicating that WMT via enema may be a viable therapeutic strategy for this population for treating CDI.
基金Supported by National Natural Science Foundation of China,No.82170638Natural Science Foundation of the Science and Technology Commission of Shanghai Municipality,No.23ZR1458300+1 种基金Key Discipline Project of Shanghai Municipal Health System,No.2024ZDXK0004and Pujiang Project of Shanghai Magnolia Talent Plan,No.24PJD098.
文摘Colorectal cancer(CRC)is ranked as the third most common tumor globally,representing approximately 10%of all cancer cases,and is the second primary cause of cancer-associated mortality.Existing therapeutic approaches demonstrate limited efficacy against CRC,partially due to the immunosuppressive tumor microenvironment(TME).In recent years,substantial evidence indicates that dysbiosis of the gut microbiota and its metabolic products is closely associated with the initiation,progression,and prognostic outcomes of CRC.In this minireview,we systematically elaborate on how these microbes and their metabolites directly impair intestinal epithelial integrity,activate cancer-associated fibroblasts,remodel tumor vasculature,and critically,sculpt an immunosuppressive landscape by modulating T cells,dendritic cells,and tumor-associated macrophages.We highlight the translational potential of targeting the gut microbiota,including fecal microbiota transplantation,probiotics,and engineered microbial systems,to reprogram the TME and overcome resistance to immunotherapy and chemotherapy.A deeper understanding of the microbiota-TME axis is essential for developing novel diagnostic and therapeutic paradigms for CRC.
基金supported by the European Union-Next Generation EU,Mission 4 Component 1,Project Title:“Gut and Neuro Muscular system:investigating the impact of microbiota on nerve regeneration and muscle reinnervation after peripheral nerve injury”,CUP D53D23007770006,MUR:20227YB93W,to GR。
文摘The gut microbiota:The human body is colonized by a diverse and complex microbial community–including bacteria,viruses,archaea,and unicellular eukaryotes–that plays a central role in human wellbeing.Indeed,microbiota is crucial for several functions,including host metabolism,physiology,maintenance of the intestinal epithelial integrity,nutrition,and immune function,earning it the designation of a“vital organ”(Guinane and Cotter,2013).
文摘We read with great interest the study by Zhang et al on Yiyi Fuzi Baijiang powder(YFB),which exemplifies the power of modern methods to validate traditional Chinese medicine(TCM).The key insight is that YFB doesn’t merely alter“good”or“bad”bacteria but restores the gut microbiota’s holistic equilibrium.This is powerfully shown by its paradoxical reduction of anaerobic probiotics like Bifidobacterium,rectifying the diseased,hypoxic environment,causing their aberrant overgrowth.This challenges the conventional probiotic paradigm and underscores a core TCM principle:Herbal formulas treat disease by restoring the body’s overall functional balance.Future research should focus on the interplay between herbal components,intestinal oxygen,and microbial metabolites to further unravel this sophisticated dialogue.
基金Haoran Zhao would like to acknowledge the support provided by China Scholarship Council(CSC)of the Ministry of Education,P.R.China(CSC No.202206850006)supported by funding from VLAIO with project number(HBC.2023.0172),HEPPY Markers-Establishment of biomarkers of Health and Eubiosis in Pigs and Poultry.
文摘Extensive evidence demonstrates that a healthy and well-balanced gut microbiota profoundly influences host nutrient absorption,immunity,and metabolism.Unlike mammals,early microbiota colonization in commercial poultry largely depends on the environment as chicks hatch in incubators under a relatively sterile environment(egg and incubator sterilization)without maternal-offspring interaction.The early gut microbiota remains unsaturated,providing a critical window for modulation and influencing the subsequent microbiota succession,which may have long-term health outcomes.Microbiota transplantation(MT)involves transferring the microbiota from a donor to a recipient to modulate the recipient’s microbiota toward a desired state.Successfully applied in human medicine,MT is also gaining attention in poultry production to modulate intestinal health.This review comprehensively explores factors affecting MT,its mechanisms,and its potential applications in chickens,providing insights for further research and commercial use.
文摘Colorectal cancer(CRC)is increasingly recognized as a multifactorial disease influenced by hereditary,environmental,and microbial factors.This article explores recent insights into the role of gut microbiota dysbiosis in CRC patho-genesis and progression.Key differences in microbial composition,characterized by enrichment of pro-carcinogenic species such as Fusobacterium nucleatum and Bacteroides fragilis and depletion of beneficial commensals like Faecalibacterium prausnitzii,have been identified alongside changes in microbial metabolites such as short-chain fatty acids and secondary bile acids.We discuss immune system modulation by the microbiota,formation of bacterial biofilms,and the activation of host pathways such as the urea cycle during tumorigenesis.Special attention is given to therapeutic innovations,including microbiota-informed precision modelling,synthetic biology-based engineered probiotics,and evolving altern-atives to fecal microbiota transplantation.These integrative strategies represent promising tools in the era of personalized oncology for CRC.
基金financially supported by the National Natural Science Foundation of China,No.823 74552 (to WP)the Science and Technology Innovation Program of Hunan Province,No.2022RC1220 (to WP)+1 种基金the Natural Science Foundation of Hunan Province of China,Nos.2020JJ4803 (to WP),2022JJ40723 (to MY)the Scientific Research Launch Project for New Employees of the Second Xiangya Hospital of Central South University (to MY)
文摘Alzheimer’s disease not only affects the brain,but also induces metabolic dysfunction in peripheral organs and alters the gut microbiota.The aim of this study was to investigate systemic changes that occur in Alzheimer’s disease,in particular the association between changes in peripheral organ metabolism,changes in gut microbial composition,and Alzheimer’s disease development.To do this,we analyzed peripheral organ metabolism and the gut microbiota in amyloid precursor protein-presenilin 1(APP/PS1)transgenic and control mice at 3,6,9,and 12 months of age.Twelve-month-old APP/PS1 mice exhibited cognitive impairment,Alzheimer’s disease-related brain changes,distinctive metabolic disturbances in peripheral organs and fecal samples(as detected by untargeted metabolomics sequencing),and substantial changes in gut microbial composition compared with younger APP/PS1 mice.Notably,a strong correlation emerged between the gut microbiota and kidney metabolism in APP/PS1 mice.These findings suggest that alterations in peripheral organ metabolism and the gut microbiota are closely related to Alzheimer’s disease development,indicating potential new directions for therapeutic strategies.
基金Supported by Research Project of the Chinese Digestive Early Cancer Physicians'Joint Growth Program,No.GTCZ-2021-AH-34-0012.
文摘This letter addresses the recently published manuscript by Darnindro et al,which investigates the diversity and composition of colonic mucosal microbiota in Indonesian patients with and without colorectal cancer(CRC).Although the analysis revealed no statistically significant differences in alpha diversity between the CRC and non-CRC groups,the authors identified notable distinctions in the composition and diversity of colonic mucosal microbiota among patients with CRC compared to those without.At the genus level,a statistically significant difference in microbiota composition was documented between the two cohorts.Specifically,the genera Bacteroides,Campylobacter,Peptostreptococcus,and Parvimonas were found to be elevated in individuals with CRC,while Faecalibacterium,Haemophilus,and Phocaeicola were more prevalent in the non-CRC group.
基金supported by the Natural Science Foundation of Hubei Province(2024AFD225)the Major Task Innovation Project of Hubei Province(2023BEB011)+1 种基金the Natural Science Foundation of Hubei Province(2023AFB403)the Central Guided Local Science and Technology Development Special Project of Hubei Province(2019ZYYD069)。
文摘Depression poses a considerable threat to global health,underscoring the critical need for safe treatments.Because of its homology of medicine and food,Gardeniae Fructus is widely used in clinical and everyday life contexts.Gardeniae Fructus oil(OGF)is a waste byproduct of the food industry with promising recycling potential.While previous research has demonstrated the antidepressant effects of OGF,the precise mechanism remains unclear.To fill this gap in the literature,this paper elucidates the composition and potential antidepressant mechanism of OGF.According to the results,OGF is mainly composed of fatty acids and unsaponifiable matter.OGF could effectively attenuate depression-like behaviors in mice with chronic unpredictable mild stress by modulating the microbiota-gut-brain axis.Mechanisms include improving gut dysbiosis,regulating short-chain fatty acids,protecting the intestinal barrier function,reducing hippocampal damage,and alleviating neuroinflammation by inhibiting the activation of the TLR4/NF-κB/NLRP3 pathway.Fecal microbiota transplantation experiments confirmed the involvement of the gut microbiota in the modulation of depression-like behavior by OGF.This study establishes the antidepressant effects of OGF as well as the underlying mechanism,demonstrating its potential as a novel dietary intervention for depression treatment.
文摘Inflammatory bowel disease,particularly Crohn's disease(CD),has been linked to modifications in mesenteric adipose tissue(MAT)and the phenomenon known as"creeping fat"(CrF).The presence of CrF is believed to serve as a predictor for early clinical recurrence following surgical intervention in patients with CD.Notably,the incorporation of the mesentery during ileocolic resection for CD has been correlated with a decrease in surgical recurrence,indicating the significant role of MAT in the pathogenesis of CD.While numerous studies have indicated that dysbiosis of the gut microbiota is a critical factor in the development of CD,the functional implications of translocated microbiota within the MAT of CD patients remain ambiguous.This manuscript commentary discusses a recent basic research conducted by Wu et al.In their study,intestinal bacteria from individuals were transplanted into CD model mice,revealing that fecal microbiota trans-plantation(FMT)from healthy donors alleviated CD symptoms,whereas FMT from CD patients exacerbated these symptoms.Importantly,FMT was found to affect intestinal permeability,barrier function,and the levels of proinflammatory factors and adipokines.Collectively,these findings suggest that targeting MAT and CrF may hold therapeutic potential for patients with CD.However,the study did not evaluate the composition of the intestinal microbiota of the donors or the subsequent alterations in the gut microbiota.Overall,the gut microbiota plays a crucial role in the histopathology of CD,and thus,targeting MAT and CrF may represent a promising avenue for treatment in this patient population.
文摘Microorganisms such as bacteria,fungi,viruses,parasites living in the human intestine constitute the human intestinal microbiota.Dysbiosis refers to composi-tional and quantitative changes that negatively affect healthy gut microbiota.In recent years,with the demonstration that many diseases are associated with dysbiosis,treatment strategies targeting the correction of dysbiosis in the treat-ment of these diseases have begun to be investigated.Faecal microbiota trans-plantation(FMT)is the process of transferring faeces from a healthy donor to another recipient in order to restore the gut microbiota and provide a therapeutic benefit.FMT studies have gained popularity after probiotic,prebiotic,symbiotic studies in the treatment of dysbiosis and related diseases.FMT has emerged as a potential new therapy in the treatment of allergic diseases as it is associated with the maintenance of intestinal microbiota and immunological balance(T helper 1/T helper 2 cells)and thus suppression of allergic responses.In this article,the definition,application,safety and use of FMT in allergic diseases will be discussed with current data.
文摘The gut microbiota plays a pivotal role in the pathogenesis of liver diseases,particularly hepatic encephalopathy(HE),in which dysbiosis contributes to ammonia production,systemic inflammation,and neurocognitive dysfunction.Emerging evidence suggests that targeting the gut-liver axis through pharmacological and microbiota-based interventions can mitigate liver disease progression and HE severity.This review explored the latest therapeutic strategies aimed at modulating gut microbiota in liver disease,focusing on traditional approaches such as non-absorbable disaccharides(lactulose,lactitol),antibiotics(rifaximin),and probiotics as well as novel interventions,including postbiotics,synbiotics,and fecal microbiota transplantation.Additionally,bile acid modulators,short-chain fatty acid derivatives,and microbiome-targeted small molecules are being investigated for their potential to restore gut-liver homeostasis.We also discussed the implications of gut microbiota modulation in conditions beyond HE,such as metabolic dysfunction-associated steatotic liver disease and cirrhosis.By integrating gut microbiotatargeted therapies into liver disease management,we may develop more effective,personalized approaches to improve patient outcomes and reduce complications.
文摘The significance of gut microbiota(GM)in human health is being increasingly researched.An imbalance in GM composition,known as dysbiosis,is linked to various and other health issues.In addition,antibiotics are the primary and most significant factors leading to major changes in the composition and function of the GM,which may result in colonization by antimicrobial-resistant(AMR)pathogens.Therefore,alternative antibiotic strategies for combating AMR pathogens are urgently needed.This narrative review highlights current knowledge regarding various pertinent strategies for decolonizing bacterial pathogens from GM and emphasizes decolonization therapies’critical role in pediatric surgical disorders.Strategies such as decontamination of the digestive tract utilizing antibiotics,the use of probiotics,and particularly fecal microbiota transplantation have introduced new options for clinical treatment.These treatments show the potential to restore GM balance and have demonstrated advantages for intestinal disorders related to pediatric surgery,including inflammatory bowel disease,neonatal necrotizing enterocolitis,Hirschsprung-associated enterocolitis,and short bowel syndrome.Despite GM therapeutics,recent strategies are still in their developmental phase and exhibit challenges that need further research.Thus,potential future directions for GMtargeted decolonization therapies are under consideration.Innovative alternative strategies to combat AMR though GM modulation in disorders related to pediatric surgery appear to be promising and should continue to be prioritized for further research and development.