Gut microbiota-astrocyte axis: new insights into age-related cognitive decline.

With the rapidly aging human population, age-related cognitive decline and dementia are becoming increasingly prevalent worldwide. Aging is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota, microbial metabolites, and the functions of astrocytes. The microbiota-gut-brain axis has been the focus of multiple studies and is closely associated with cognitive function. This article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative diseases. This article also summarizes the gut microbiota components that affect astrocyte function, mainly through the vagus nerve, immune responses, circadian rhythms, and microbial metabolites. Finally, this article summarizes the mechanism by which the gut microbiota-astrocyte axis plays a role in Alzheimer's and Parkinson's diseases. Our findings have revealed the critical role of the microbiota-astrocyte axis in age-related cognitive decline, aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.

The oral-gut microbiome axis in inflammatory bowel disease: from inside to insight.

Inflammatory bowel disease (IBD) is an idiopathic and persistent inflammatory illness of the bowels, leading to a substantial burden on both society and patients due to its high incidence and recurrence. The pathogenesis of IBD is multifaceted, partly attributed to the imbalance of immune responses toward the gut microbiota. There is a correlation between the severity of the disease and the imbalance in the oral microbiota, which has been discovered in recent research highlighting the role of oral microbes in the development of IBD. In addition, various oral conditions, such as angular cheilitis and periodontitis, are common extraintestinal manifestations (EIMs) of IBD and are associated with the severity of colonic inflammation. However, it is still unclear exactly how the oral microbiota contributes to the pathogenesis of IBD. This review sheds light on the probable causal involvement of oral microbiota in intestinal inflammation by providing an overview of the evidence, developments, and future directions regarding the relationship between oral microbiota and IBD. Changes in the oral microbiota can serve as markers for IBD, aiding in early diagnosis and predicting disease progression. Promising advances in probiotic-mediated oral microbiome modification and antibiotic-targeted eradication of specific oral pathogens hold potential to prevent IBD recurrence.

Lacticaseibacillus rhamnosus GG alleviates sleep deprivation-induced intestinal barrier dysfunction and neuroinflammation in mice.

Consuming probiotic products is a solution that people are willing to choose to augment health. As a global health hazard, sleep deprivation (SD) can cause both physical and mental diseases. The present study investigated the protective effects of Lacticaseibacillus rhamnosus GG (LGG), a widely used probiotic, on a SD mouse model. Here, it has been shown that SD induced intestinal damage in mice, while LGG supplementation attenuated disruption of the intestinal barrier and enhanced the antioxidant capacity. Microbiome analysis revealed that SD caused dysbiosis in the gut microbiota, characterized by increased levels of Clostridium XlVa, Alistipes, and Desulfovibrio, as well as decreased levels of Ruminococcus, which were partially ameliorated by LGG. Moreover, SD resulted in elevated pro-inflammatory cytokine concentrations in both the intestine and the brain, while LGG provided protection in both organs. LGG supplementation significantly improved locomotor activity in SD mice. Although heat-killed LGG showed some protective effects in SD mice, its overall efficacy was inferior to that of live LGG. In terms of mechanism, it was found that AG1478, an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, could diminish the protective effects of LGG. In conclusion, LGG demonstrated the ability to alleviate SD-induced intestinal barrier dysfunction through EGFR activation and alleviate neuroinflammation.

A Saccharomyces boulardii-derived antioxidant protein, thioredoxin, ameliorates intestinal inflammation through transactivating epidermal growth factor receptor.

Saccharomyces boulardii (Sb) is a probiotic yeast for the treatment of gastrointestinal disorders, including inflammatory bowel disease (IBD). Little is known about the modulatory capacity of the Sb in IBD. Here, we found that oral gavage of Sb supernatant (SbS) alleviated gut inflammation, protected the intestinal barrier, and reversed DSS-induced down-regulated activation of epidermal growth factor receptor (EGFR) in colitis. Mass spectrum analysis showed that thioredoxin (Trx) is one of the critical secreted soluble proteins participating in EGFR activation detected in SbS. Trx exerted an array of significant effects on anti-inflammatory activity, including alleviating inflammation, protecting gut barrier, suppressing apoptosis, as well as reducing oxidative stress. Mechanistically, Trx promoted EGFR ligand gene expression and transactivated EGFR in a concentration-dependent manner. EGFR kinase inhibitor could block Trx-mediated preventive effects of intestinal epithelial injury. Our data suggested that Sb-derived soluble protein Trx could serve as a potential prophylactic, as a novel postbiotic against colitis, which provides a new strategy for the precision prevention and treatment of IBD.

Hypoxia promotes histone H3K9 lactylation to enhance LAMC2 transcription in esophageal squamous cell carcinoma.

Hypoxia promotes tumorigenesis and lactate accumulation in esophageal squamous cell carcinoma (ESCC). Lactate can induce histone lysine lactylation (Kla, a recently identified histone marks) to regulate transcription. However, the functional consequence of histone Kla under hypoxia in ESCC remains to be explored. Here, we reveal that hypoxia facilitates histone H3K9la to enhance LAMC2 transcription for proliferation of ESCC. We found that global level of Kla was elevated under hypoxia, and thus identified the landscape of histone Kla in ESCC by quantitative proteomics. Furthermore, we show a significant increase of H3K9la level induced by hypoxia. Next, MNase ChIP-seq and RNA-seq analysis suggest that H3K9la is enriched at the promoter of cell junction genes. Finally, we demonstrate that the histone H3K9la facilitates the expression of LAMC2 for ESCC invasion by in vivo and in vitro experiments. Briefly, our study reveals a vital role of histone Kla triggered by hypoxia in cancer.

Lactobacillus rhamnosus GG coating with nanocomposite ameliorates intestinal inflammation.

The steady increase in the prevalence of inflammatory bowel disease (IBD) is regarded as a worldwide health issue. Gut microorganisms could modulate host immune and metabolic status and are associated with health effects. Probiotics, Lactobacillus rhamnosus GG (LGG), are beneficial microorganisms that ameliorate disease and exert advantageous effects on intestinal homeostasis. However, the viability of probiotics will suffer from various risk factors in the digestive tract. In this view, we developed a probiotic coating with nanocomposite using tannic acid (TA) and casein phosphopeptide (CPP) through layer-by-layer technology to overcome the challenges after oral administration. LGG showed an improved survival rate in simulated gastrointestinal conditions after coated. The coating (LGG/TA-Mg2+/CPP) had potent reactive oxygen species (ROS) scavenging ability and improved the survival rate of colorectal epithelial cells after H2O2 stimulation. In DSS-induced colitis, administration of LGG/TA-Mg2+/CPP ameliorated intestinal inflammation and reduced the disruption of barrier function. Furthermore, LGG/TA-Mg2+/CPP increased the abundance and diversity of the gut microbiota. In the mouse model of DSS colitis, LGG/TA-Mg2+/CPP can better activate the EGFR/AKT signaling pathway, thereby protecting the epithelial barrier function of the colon epithelium. In conclusion, the probiotic coating with nanocomposite may become a delivery platform for probiotics applied to IBD.

Gut microbiota metabolite indole-3-acetic acid maintains intestinal epithelial homeostasis through mucin sulfation.

The global incidence and prevalence of inflammatory bowel disease (IBD) are gradually increasing. A high-fat diet (HFD) is known to disrupt intestinal homeostasis and aggravate IBD, yet the underlying mechanisms remain largely undefined. Here, a positive correlation between dietary fat intake and disease severity in both IBD patients and murine colitis models is observed. A HFD induces a significant decrease in indole-3-acetic acid (IAA) and leads to intestinal barrier damage. Furthermore, IAA supplementation enhances intestinal mucin sulfation and effectively alleviates colitis. Mechanistically, IAA upregulates key molecules involved in mucin sulfation, including 3'-phosphoadenosine 5'-phosphosulfate synthase 2 (Papss2) and solute carrier family 35 member B3 (Slc35b3), the synthesis enzyme and the transferase of 3'-phosphoadenosine-5'-phosphosulfate (PAPS), via the aryl hydrocarbon receptor (AHR). More importantly, AHR can directly bind to the transcription start site of Papss2. Oral administration of Lactobacillus reuteri, which can produce IAA, contributes to protecting against colitis and promoting mucin sulfation, while the modified L. reuteri strain lacking the iaaM gene (LactobacillusΔiaaM) and the ability to produce IAA fail to exhibit such effects. Overall, IAA enhances intestinal mucin sulfation through the AHR-Papss2-Slc35b3 pathway, contributing to the protection of intestinal homfeostasis.

A HFD can lead to the development of colitis by disrupting tryptophan metabolism in the gut microbiome and lowering levels of IAA. Supplementation with IAA has been shown to alleviate colitis in mice and improve intestinal barrier function. It is believed that IAA may activate the AHR to upregulate the expression of Papss2 and Slc35b3, promoting sulfation modification of mucins and protecting the intestinal barrier. HFD, high-fat diet; AHR, aryl hydrocarbon receptor; IAA, indole-3-acetic acid; Papss2, 3'-phosphoadenosine 5'-phosphosulfate synthase 2; Slc35b3, solute carrier family 35 member B3.

Structural Distortion of g-C3N4 Induced by a Schiff Base Reaction for Efficient Photocatalytic H2 Evolution.

Photocatalytic H2 evolution by water splitting is a promising approach to address the challenges of environmental pollution and energy scarcity. Graphitic carbon nitride (g-C3N4) has emerged as a star photocatalyst because of its numerous advantages. To address the limitations of traditional g-C3N4, namely its inadequate visible light response and rapid recombination of photogenerated carriers, we employed a schiff base reaction to synthesize -C=N- doped g-C3N4. The introduction of -C=N- groups at the bridging nitrogen sites induced structural distortion in g-C3N4, facilitating n-π* electronic transitions from the lone pair electrons of nitrogen atom and extending light absorption up to 600 nm. Moreover, the presence of heterogeneous π-conjugated electron distribution effectively traps photogenerated electrons and enhances charge carrier separation. Benefiting from its expanded spectral response range, unique electronic properties, increased specific surface area, the doped g-C3N4 exhibited outstanding photocatalytic H2 evolution performance of 1050.13 µmol/g/h. The value was 5.9 times greater than the pristine g-C3N4.

Transferability of Machine Learning Models for Geogenic Contaminated Groundwaters.

Machine learning models show promise in identifying geogenic contaminated groundwaters. Modeling in regions with no or limited samples is challenging due to the need for large training sets. One potential solution is transferring existing models to such regions. This study explores the transferability of high fluoride groundwater models between basins in the Shanxi Rift System, considering six factors, including modeling methods, predictor types, data size, sample/predictor ratio (SPR), predictor range, and data informing. Results show that transferability is achieved only when model predictors are based on hydrochemical parameters rather than surface parameters. Data informing, i.e., adding samples from challenging regions to the training set, further enhances the transferability. Stepwise regression shows that hydrochemical predictors and data informing significantly improve transferability, while data size, SPR, and predictor range have no significant effects. Additionally, despite their stronger nonlinear capabilities, random forests and artificial neural networks do not necessarily surpass logistic regression in transferability. Lastly, we utilize the t-SNE algorithm to generate low-dimensional representations of data from different basins and compare these representations to elucidate the critical role of predictor types in transferability.

Dietary emulsifier polysorbate 80 exposure accelerates age-related cognitive decline.

Gut microbial homeostasis is crucial for the health of cognition in elderly. Previous study revealed that polysorbate 80 (P80) as a widely used emulsifier in food industries and pharmaceutical formulations could directly alter the human gut microbiota compositions. However, whether long-term exposure to P80 could accelerate age-related cognitive decline via gut-brain axis is still unknown. Accordingly, in this study, we used the senescence accelerated mouse prone 8 (SAMP8) mouse model to investigate the effects of the emulsifier P80 intake (1 % P80 in drinking water for 12 weeks) on gut microbiota and cognitive function. Our results indicated that P80 intake significantly exacerbated cognitive decline in SAMP8 mice, along with increased brain pathological proteins deposition, disruption of the blood-brain barrier and activation of microglia and neurotoxic astrocytes. Besides, P80 intake could also induce gut microbiota dysbiosis, especially the increased abundance of secondary bile acids producing bacteria, such as Ruminococcaceae, Lachnospiraceae, and Clostridium scindens. Moreover, fecal microbiota transplantation from P80 mice into 16-week-old SAMP8 mice could also exacerbated cognitive decline, microglia activation and intestinal barrier impairment. Intriguingly, the alterations of gut microbial composition significantly affected bile acid metabolism profiles after P80 exposure, with markedly elevated levels of deoxycholic acid (DCA) in serum and brain tissue. Mechanically, DCA could activate microglial and promote senescence-associated secretory phenotype production through adenosine triphosphate-binding cassette transporter A1 (ABCA1) importing lysosomal cholesterol. Altogether, the emulsifier P80 accelerated cognitive decline of aging mice by inducing gut dysbiosis, bile acid metabolism alteration, intestinal barrier and blood brain barrier disruption as well as neuroinflammation. This study provides strong evidence that dietary-induced gut microbiota dysbiosis may be a risk factor for age-related cognitive decline.

Microbial metabolite deoxycholic acid-mediated ferroptosis exacerbates high-fat diet-induced colonic inflammation.

High-fat diet (HFD) has long been recognized as risk factors for the development and progression of ulcerative colitis (UC), but the exact mechanism remained elusive. Here, HFD increased intestinal deoxycholic acid (DCA) levels, and DCA further exacerbated colonic inflammation. Transcriptome analysis revealed that DCA triggered ferroptosis pathway in colitis mice. Mechanistically, DCA upregulated hypoxia-inducible factor-2α (HIF-2α) and divalent metal transporter-1 (DMT1) expression, causing the ferrous ions accumulation and ferroptosis in intestinal epithelial cells, which was reversed by ferroptosis inhibitor ferrostatin-1. DCA failed to promote colitis and ferroptosis in intestine-specific HIF-2α-null mice. Notably, byak-angelicin inhibited DCA-induced pro-inflammatory and pro-ferroptotic effects through blocking the up-regulation of HIF-2α by DCA. Moreover, fat intake was positively correlated with disease activity in UC patients consuming HFD, with ferroptosis being more pronounced. Collectively, our findings demonstrated that HFD exacerbated colonic inflammation by promoting DCA-mediated ferroptosis, providing new insights into diet-related bile acid dysregulation in UC.

The diagnostic value of tenascin-C in acute aortic syndrome.

OBJECTIVES: Misdiagnosis of acute aortic syndrome (AAS) significantly increases mortality. Tenascin-C (TN-C) is an extracellular matrix glycoprotein related to cardiovascular injury. The elevation of TN-C in AAS and whether it can discriminate sudden-onset of acute chest pain in Chinese remains unclear. METHODS: We measured the plasma concentration of TN-C by ELISA in a cohort of 376 patients with chest or back pain. Measures to discriminate AAS from acute coronary syndrome (ACS) were compared and calculated. RESULTS: From October 2016 to September 2021, 376 undiagnosed patients with chest or back pain were enrolled. 166 of them were finally diagnosed as AAS, 100 were ACS and 110 without cardiovascular diseases (NCV). TN-C was significantly elevated in AAS at 18.18 ng/mL (IQR: 13.10-27.68) compared with 7.51 ng/mL (IQR: 5.67-11.38) in ACS (P < 0.001) and 3.68 ng/mL (IQR: 2.50-5.29) in NCV (P < 0.001). There was no significant difference in TN-C level among the subtypes of AAS. Of the 166 AAS patients, the peaked level of TN-C was at acute stage (P = 0.012), then a slight of decrease was observed at subacute stage. The area under receiver operating characteristic curve for AAS patients versus NCV was 0.979 (95% CI: 0.964-0.994) for TN-C. At a cutoff level of 11.474 ng/mL, TN-C has a sensitivity of 76.0%, specificity of 85.5%, accuracy of 82.0%, positive predictive value (PPV) of 76.0%, negative predictive value (NPV) of 85.5%. Diagnostic performance of TN-C was superior to D-dimer and hs-cTnT. CONCLUSIONS: The concentration of serum TN-C in AAS patients was significantly higher than that in ACS patients and NCV. TN-C could be a new biomarker to distinguish AAS patients in the early stage after symptoms onset from other pain diseases.

Safety and efficacy of Cox-Maze procedure for atrial fibrillation during mitral valve surgery: a meta-analysis of randomized controlled trials.

BACKGROUND: Cox-Maze procedure is currently the gold standard treatment for atrial fibrillation (AF). However, data on the effectiveness of the Cox-Maze procedure after concomitant mitral valve surgery (MVS) are not well established. The aim of this study was to assess the safety and efficacy of Cox-Maze procedure versus no-maze procedure n in AF patients undergoing mitral valve surgery through a systematic review of the literature and meta-analysis. METHODS: A systematic search on PubMed/MEDLINE, EMBASE, and Cochrane Central Register of Clinical Trials (Cochrane Library, Issue 02, 2017) databases were performed using three databases from their inception to March 2023, identifying all relevant randomized controlled trials (RCTs) comparing Cox-Maze procedure versus no procedure in AF patients undergoing mitral valve surgery. Data were extracted and analyzed according to predefined clinical endpoints. RESULTS: Nine RCTs meeting the inclusion criteria were included in this systematic review with 663 patients in total (341 concomitant Cox-Maze with MVS and 322 MVS alone). Across all studies with included AF patients undergoing MV surgery, the concomitant Cox-Maze procedure was associated with significantly higher sinus rhythm rate at discharge, 6 months, and 12 months follow-up when compared with the no-Maze group. Results indicated that there was no significant difference between the Cox-Maze and no-Maze groups in terms of 1 year all-cause mortality, pacemaker implantation, stroke, and thromboembolism. CONCLUSIONS: Our systematic review suggested that RCTs have demonstrated the addition of the Cox-Maze procedure for AF leads to a significantly higher rate of sinus rhythm in mitral valve surgical patients, with no increase in the rates of mortality, pacemaker implantation, stroke, and thromboembolism.

Gut microbiota and metabolites as predictors of biologics response in inflammatory bowel disease: A comprehensive systematic review.

Nonresponse to biologic agents in patients with inflammatory bowel disease (IBD) poses a significant public health burden, and the prediction of response to biologics offers valuable insights for IBD management. Given the pivotal role of gut microbiota and their endogenous metabolites in IBD, we conducted a systematic review to investigate the potential of fecal microbiota and mucosal microbiota and endogenous metabolomic markers as predictors for biotherapy response in IBD patients. A total of 38 studies were included in the review. Following anti-TNF-α treatment, the bacterial community characteristics of IBD patients exhibited a tendency to resemble those observed in healthy controls, indicating an improved clinical response. The levels of endogenous metabolites butyrate and deoxycholic acid were significantly associated with clinical remission following anti-TNF-α therapy. IBD patients who responded well to vedolizumab treatment had higher levels of specific bacteria that produce butyrate, along with increased levels of metabolites such as butyrate, branched-chain amino acids and acetamide following vedolizumab treatment. Crohn's disease patients who responded positively to ustekinumab treatment showed higher levels of Faecalibacterium and lower levels of Escherichia/Shigella. In conclusion, fecal microbiota and mucosal microbiota as well as their endogenous metabolites could provide a predictive tool for assessing the response of IBD patients to various biological agents and serve as a valuable reference for precise drug selection in clinical IBD patients.

Selection strategy of second-line biologic therapies in adult patients with ulcerative colitis following prior biologic treatment failure: Systematic review and meta-analysis.

BACKGROUND: Optimizing second-line biologic therapies for adult ulcerative colitis (UC) post first-line failure is essential. OBJECTIVE: Compare second-line biologic therapy efficacy in adult UC patients with prior treatment failure. METHODS: A comprehensive search of electronic databases up to May 2023 was conducted to assess second-line biologic therapy efficacy using a random effects model. Parameters analyzed included clinical remission rate, clinical response rate, mucosal healing rate, annual discontinuation rate, and colectomy rates. RESULTS: Forty-three research papers were analyzed. Clinical remission rates for second-line biologics were ranked at 6-14 weeks: Infliximab (30%) was followed by Vedolizumab (29%), Ustekinumab (27%), and Adalimumab (19%). At 52-54 weeks, the order shifted, with Vedolizumab (35%) followed by Infliximab (32%), Ustekinumab (31%), and Adalimumab (26%). The mucosal healing rate was 21%, ranked as: Infliximab (31%), Vedolizumab (21%), Adalimumab (21%), and Ustekinumab (14%). The annual discontinuation rate stood at 20%, with Adalimumab (25%), Vedolizumab (18%), Infliximab (17%), and Ustekinumab (16%). Discontinuation rates due to primary failure (PF), secondary failure (SF), and adverse events (AE) were 6%, 12%, and 3%, respectively. The annual colectomy rate was 9%, with Adalimumab (15%) followed by Vedolizumab (10%), Ustekinumab (9%), and Infliximab (5%), and colectomy rates of 10% due to PF, 12% due to SF, and 4% due to AE. CONCLUSION: For UC patients with first-line treatment failure, it is recommended to prioritize infliximab or vedolizumab as second-line biologic therapies, while avoiding adalimumab as the primary choice. Further clinical trials are necessary to assess ustekinumab efficacy accurately.

Microbial metabolite trimethylamine-N-oxide induces intestinal carcinogenesis through inhibiting farnesoid X receptor signaling.

PURPOSE: Microbial dysbiosis is considered as a hallmark of colorectal cancer (CRC). Trimethylamine-N-oxide (TMAO) as a gut microbiota-dependent metabolite has recently been implicated in CRC development. Nevertheless, evidence relating TMAO to intestinal carcinogenesis remains largely unexplored. Herein, we aimed to examine the crucial role of TMAO in CRC progression. METHODS: Apcmin/+ mice were treated with TMAO or sterile PBS for 14 weeks. Intestinal tissues were isolated to evaluate the effects of TMAO on the malignant transformation of intestinal adenoma. The gut microbiota of mouse feces was detected by 16S rRNA sequencing analysis. HCT-116 cells were used to provide further evidence of TMAO on the progression of CRC. RESULTS: TMAO administration increased tumor cell and stem cell proliferation, and decreased apoptosis, accompanied by DNA damage and gut barrier impairment. Gut microbiota analysis revealed that TMAO induced changes in the intestinal microbial community structure, manifested as reduced beneficial bacteria. Mechanistically, TMAO bound to farnesoid X receptor (FXR), thereby inhibiting the FXR-fibroblast growth factor 15 (FGF15) axis and activating the Wnt/ß-catenin signaling pathway, whereas the FXR agonist GW4064 could blunt TMAO-induced Wnt/ß-catenin pathway activation. CONCLUSION: The microbial metabolite TMAO can enhance intestinal carcinogenesis by inhibiting the FXR-FGF15 pathway.

Exposure to prescribed medication in early life and impacts on gut microbiota and disease development.

The gut microbiota during early life plays a crucial role in infant development. This microbial-host interaction is also essential for metabolism, immunity, and overall human health in later life. Early-life pharmaceutical exposure, mainly referring to exposure during pregnancy, childbirth, and infancy, may change the structure and function of gut microbiota and affect later human health. In this Review, we describe how healthy gut microbiota is established in early life. We summarise the commonly prescribed medications during early life, including antibiotics, acid suppressant medications and other medications such as antidepressants, analgesics and steroid hormones, and discuss how these medication-induced changes in gut microbiota are involved in the pathological process of diseases, including infections, inflammatory bowel disease, metabolic diseases, allergic diseases and neurodevelopmental disorders. Finally, we review some critical methods such as dietary therapy, probiotics, prebiotics, faecal microbiota transplantation, genetically engineered phages, and vagus nerve stimulation in early life, aiming to provide a new strategy for the prevention of adverse health outcomes caused by prescribed medications exposure in early life.

Fecal microbiota transplantation: no longer cinderella in tumour immunotherapy.

The incidence of cancer has shown a great increase during the past decades and poses tough challenges to cancer treatment. Anti-tumour immunotherapy, represented by immune checkpoint inhibitors (ICIs), possesses favorable remission in unrestricted spectrum of cancer types. However, its efficacy seems to be heterogeneous among accumulating studies. Emerging evidences suggest that gut microbiota can modulate anti-tumour immuno-response and predict clinical prognosis. Therefore, remodeling microbiota characteristics with fecal microbiota transplantation (FMT) may be capable of reinforcing host ICIs performance by regulating immune-tumour cell interactions and altering microbial metabolites, thereby imperceptibly shifting the tumour microenvironment. However, the long-term safety of FMT is under concern, which calls for more rigorous screening. In this review, we examine current experimental and clinical evidences supporting the FMT efficacy in boosting anti-tumour immuno-response and lessening tumour-related complications. Moreover, we discuss the challenges in FMT and propose feasible resolutions, which may offer crucial guidance for future clinical operations.

Ferroptosis: a promising candidate for exosome-mediated regulation in different diseases.

Ferroptosis is a newly discovered form of cell death that is featured in a wide range of diseases. Exosome therapy is a promising therapeutic option that has attracted much attention due to its low immunogenicity, low toxicity, and ability to penetrate biological barriers. In addition, emerging evidence indicates that exosomes possess the ability to modulate the progression of diverse diseases by regulating ferroptosis in damaged cells. Hence, the mechanism by which cell-derived and noncellular-derived exosomes target ferroptosis in different diseases through the system Xc-/GSH/GPX4 axis, NAD(P)H/FSP1/CoQ10 axis, iron metabolism pathway and lipid metabolism pathway associated with ferroptosis, as well as its applications in liver disease, neurological diseases, lung injury, heart injury, cancer and other diseases, are summarized here. Additionally, the role of exosome-regulated ferroptosis as an emerging repair mechanism for damaged tissues and cells is also discussed, and this is expected to be a promising treatment direction for various diseases in the future. Video Abstract.