Alterations in the gut microbiota may contribute to the development of inflammatory bowel disease (IBD). Chlorogenic acid (CGA), a product of the esterification of caffeic acid and quinic acid, is one of the most abundant polyphenols in the human diet and has potential beneficial effects on gut function. However, the underlying mechanisms remain unclear. In this study, the pharmacological effects of CGA on colitis and the potential underlying mechanisms were investigated.

A mouse model of colitis was induced via the use of 4 % dextran sulfate sodium (DSS), and the mice were treated with 200 mg/kg CGA. Body weight, colon length, colon tissue pathology, and plasma and colon inflammatory cytokine levels were assessed. RNA sequencing was used to detect changes in gene expression in mouse colon tissues, and 16S rRNA sequencing was used to analyze the composition and structure of the gut microbiota. Fecal metabolomic analysis was performed, and fecal microbiota transplantation (FMT) was used to evaluate the contribution of the gut microbiota.

CGA significantly alleviated DSS-induced colitis, alleviating intestinal mucosal barrier damage and gut microbiota dysbiosis. It significantly enriched bacteria that produce short-chain fatty acids (SCFAs). CGA inhibited the accumulation of purine metabolites derived from the microbiota and suppressed immune-related signaling cascades, exerting immunomodulatory effects. Furthermore, the gut microbiota of CGA-treated mice alleviated DSS-induced colitis through FMT.

CGA alleviates colitis in a gut microbiota-dependent manner, potentially providing a new strategy for the treatment of IBD.

Addictive substance use disorder has a wide range of effects on the intestinal barrier, including damage to the biological, chemical, mechanical, and immune barriers. Damage to the intestinal barrier caused by addictive substance use disorder allows harmful substances and bacteria to cross the intestinal barrier into the circulatory system, leading to systemic inflammatory responses and immune imbalances. In addition, the interaction between the gut flora and the central nervous system is recognized as an important component of the gut-brain axis. Gut barrier damage leads to dysbiosis, which in turn affects brain function by activating immune cells and releasing inflammatory factors. This may lead to altered mood and cognitive function, increased addictive substance cravings, and dependence. Recent research has indicated that reshaping the gut-brain axis and adjusting the composition and abundance of gut microbiota holds promise in alleviating withdrawal symptoms with addictive substance dependence. This article reviews the effects of addictive substance use disorder on the intestinal barrier and explores the possibility of improving addictive substance dependence by treating gut barrier damage.

The intestinal microbiome constitutes a sophisticated and massive ecosystem pivotal for maintaining gastrointestinal equilibrium and mucosal immunity via diverse pathways. The gut microbiota is continuously reshaped by multiple environmental factors, thereby influencing overall wellbeing or predisposing individuals to disease state. Many observations reveal an altered microbiome composition in individuals with autoimmune conditions, coupled with shifts in metabolic profiles, which has spurred ongoing development of therapeutic interventions targeting the microbiome. This review delineates the microbial consortia of the intestine, their role in sustaining gastrointestinal stability, the association between the microbiome and immune-mediated pathologies, and therapeutic modalities focused on microbiome modulation. We emphasize the entire role of the intestinal microbiome in human health and recommend microbiome modulation as a viable strategy for disease prophylaxis and management. However, the application of gut microbiota modification for the treatment of immune-related diseases, such as fecal microbiota transplantation and probiotics, remain quite challenging. Therefore, more research is needed into the role and mechanisms of these therapeutics.

Inflammatory bowel disease (IBD) is an immune-mediated gastrointestinal disorder that significantly impacts the life quality of people worldwide. Genetic factors play crucial roles in the development of IBD. Tas2rs, members of the G protein-coupled receptor (GPCR) superfamily, are known for their roles in bitter taste perception. However, Tas2rs have also been identified in the gut, where they help sense luminal contents and regulate gastrointestinal hormones. Periodontal Tas2r105 has been shown to modulate innate immunity by interacting with metabolites produced by oral bacteria. In this study, we observed increased Tas2r105 in the inflammatory colons induced by dextran sulfate sodium salt (DSS). We also noted that α-gustducin, the α-subunit of GPCRs, is present in the intestine, and that α-gustducin knockout mice exhibit aggravated colitis. Based on these findings, we hypothesize that Tas2r105 may play a role in immune regulation during IBD pathogenesis. To test this hypothesis, we used Tas2r105 knockout (KO) mice in a colitis model. Our results show that the KO mice had significantly shorter colon length, more severe colon inflammation, and greater destruction of the gut barrier compared with control mice. We also observed increased recruitment of macrophages to the lamina propria mucosa in the KO mice. Microbiological analysis revealed a significant increase in Proteobacteria and Bacteroidota, with a concomitant decrease in Firmicutes after Tas2r105 knockout. Metabolomic analysis showed a significant reduction in lysophosphatidylethanolamine (LPE) levels in the KO mice, which is known to have anti-inflammatory effects. Based on these findings, we speculate that Tas2r105 may help protect the intestine from inflammation by influencing the gut microbiota composition and LPE production.IMPORTANCEIncreased Tas2r105 was detected in the inflamed colon of mice outside the tongue. Tas2r105 deletion aggravated mice colon colitis. Tas2r105 might alleviate mice colitis by downregulating the Proteobacteria and the Bacteroidota abundance in the colon. Lysophosphatidylethanolamine (LPE) might be the key metabolite that mediated the intestinal protection of Tas2r105.

The stability and metabolic functionality of donor microbiota are critical determinants of fecal microbiota transplantation (FMT) efficacy in inflammatory bowel disease (IBD). While probiotics show potential to enhance microbiota resilience, their role in optimizing donor microbiota for FMT remains underexplored.

This study investigated whether pretreatment of donor microbiota with L. plantarum GR-4 could improve FMT outcomes in a DSS-induced colitis model by modulating microbial stability, metabolic activity, and host-microbiome interactions.

Donor mice received L. plantarum GR-4 for 3 weeks to generate modified FMT (MFMT). DSS-colitis mice were treated with MFMT, conventional FMT, or 5-aminosalicylic acid (5-ASA). Multi-omics analyses and functional assays (stress resistance, engraftment efficiency) were used to evaluate therapeutic mechanisms.

GR-4 pretreatment conferred three key advantages to donor microbiota: Ecological stabilization: 1. GR-4-driven acidification (pH 3.97 vs. 4.59 for LGG, p < 0.0001) enriched butyrogenic Butyricicoccus (73 % butyrate increase, p < 0.05) and improved stress resistance to bile acids/gastric conditions (1.25 × survival vs. FMT). 2. Metabolic reprogramming: GR-4 metabolized 25.3 % of tryptophan (vs. 10.3 % for LGG) to generate immunomodulatory indoles (ILA, IAA), activating aryl hydrocarbon receptor (AHR) signaling and upregulating anti-inflammatory IL-10/IL-22. 3. Bile acid remodeling: MFMT restored sulfolithocholic acid and β-MCA levels, outperforming FMT in resolving DSS-induced dysregulation. MFMT achieved an 83 % remission rate (vs. 50 % for FMT), enhanced gut barrier integrity, and reversed colitis-associated metabolic dysregulation (e.g., elevated spermidine, 7-sulfocholic acid). Probiotic preconditioning improved donor engraftment by 1.25 × and enriched success-associated taxa (Sporobacter, Butyricimonas), while suppressing pathogens (Clostridium papyrosolvens).

L. plantarum GR-4 optimizes donor microbiota via pH-driven niche engineering, immunometabolic reprogramming, and bile acid modulation, addressing key limitations of conventional FMT. The multi-targeted efficacy of MFMT, evidenced by superior remission rates and metabolic restoration, establishes this approach as a translatable strategy for IBD therapy. This study establishes probiotic-enhanced FMT as a paradigm for precision microbiome interventions.

Stroke represents a predominant cause of mortality and disability on a global scale, impacting millions annually and exerting a considerable strain on healthcare systems. The incidence of stroke exhibits regional variability, with ischemic stroke accounting for the majority of occurrences. Post-stroke complications, such as cognitive impairment, motor dysfunction, and recurrent stroke, profoundly affect patients' quality of life. Recent advancements have elucidated the microbiota-gut-brain axis (MGBA), underscoring the complex interplay between gut health and brain function. Dysbiosis, characterized by an imbalance in gut microbiota, is significantly linked to an elevated risk of stroke and unfavorable outcomes. The MGBA plays a crucial role in modulating immune function, neurotransmitter levels, and metabolic byproducts, which may intensify neuroinflammation and impair cerebral health. This review elucidates the role of MGBA in stroke pathophysiology and explores potential gut-targeted therapeutic strategies to reduce stroke risk and promote recovery, including probiotics, prebiotics, pharmacological interventions, and dietary modifications. However, the current prevention and treatment strategies based on intestinal flora still face many problems, such as the large difference of individual intestinal flora, the stability of efficacy, and the long-term safety need to be considered. Further research needs to be strengthened to promote its better application in clinical practice.

Kawasaki disease (KD) is an acute systemic immune vasculitis with predominant involvement of the medium and small arteries. It mostly affects pediatric patients, representing the most common form of pediatric vasculitis in children less than 5 years old. Numerous diseases, especially those related to the immune system, have established links with the intestinal flora. Recent studies have investigated the intestinal flora changes throughout the management of KD. There was gut microbiota dysbiosis in pediatric KD at the acute phase, particularly the downregulation of short-chain fat acids-producing microbiota and the over-proliferation of opportunistic pathogens. The relationship between the response to therapies in individuals with KD and specific microbiota remains uncertain. Targeted microbial supplements and dietary regulation may serve as potential measures to alleviate KD complications and thus improve prognosis. This review provides an overview of the current understanding of the interplay of the gut microbiota and KD. Furthermore, it discusses the possibility of altering the gut microbiota to reinstate a healthy condition.

The gut microbiota plays a crucial role in safeguarding host health and driving the progression of intestinal diseases. Despite recent advances in the remarkable correlation between dysbiosis and extraintestinal cancers, the underlying mechanisms are yet to be fully elucidated. Pathogenic microbiota, along with their metabolites, can undermine the integrity of the gut barrier through inflammatory or metabolic pathways, leading to increased permeability and the translocation of pathogens. The dissemination of pathogens through the circulation may contribute to the establishment of an immune-suppressive environment that promotes carcinogenesis in extraintestinal organs either directly or indirectly. The oncogenic cascade always engages in the disruption of hormonal regulation and inflammatory responses, the induction of genomic instability and mutations, and the dysregulation of adult stem cell proliferation. This review aims to comprehensively summarize the existing evidence that points to the potential role of dysbiosis in the malignant transformation of extraintestinal organs such as the liver, breast, lung, and pancreas. Additionally, we delve into the limitations inherent in current methodologies, particularly the challenges associated with differentiating low loads gut-derived microbiome within tumors from potential sample contamination or symbiotic microorganisms. Although still controversial, an understanding of the contribution of translocated intestinal microbiota and their metabolites to the pathological continuum from chronic inflammation to tumors could offer a novel foundation for the development of targeted therapeutics.

Despite the known association between microorganisms and development of inflammatory bowel disease (IBD), the role of nontyphoidal Salmonella (NTS) in IBD is not adequately addressed. We aimed at elucidating the relationship between NTS infection and the risk of IBD.

Based on the National Health Insurance Research Database in Taiwan, this retrospective cohort study enrolled patients with NTS infection (exposure group; n = 4651) and those without NTS infection (comparator group; n = 4651) who were propensity score matched (1:1) by demographic data, medications, comorbidities, and index date. All patients were followed until IBD onset, individual mortality, or December 31, 2018. Cox proportional hazards regression analysis was performed to determine the hazard ratios and 95% confidence intervals (CIs). Sensitivity analyses were used for cross-validation.

The NTS group demonstrated an increased risk of IBD compared with the non-NTS groups (adjusted hazard ratio [aHR], 2.12; 95% CI, 1.62-2.78) with a higher risk of developing ulcerative colitis in the former (aHR, 2.27; 95% CI, 1.69-3.04). Nevertheless, the small sample size may contribute to lack of significant difference in Crohn's disease. Consistent findings were noted after excluding IBD diagnosed within 6 months of NTS infection (aHR, 2.28; 95% CI, 1.71-3.03), excluding those with enteritis/colitis before index date (aHR, 1.85; 95% CI, 1.28-2.68), excluding those using antibiotics for 1 month in the year before IBD onset (aHR, 1.81; 95% CI, 1.34-2.45), inverse probability of treatment weighting (aHR, 1.64; 95% CI, 1.31-2.04), and inclusion of individuals regardless of age (n = 10 431; aHR, 1.83; 95% CI, 1.53-2.19).

Patients with NTS were associated with an increased risk of developing IBD, especially ulcerative colitis.

Ulcerative colitis is a chronic disease that has not well-established etiology. The role of microbial dysregulation in its pathogenesis has been recently highlighted. Overall, microbiome alterations concern the reduction of bacterial abundance and diversity, resulting in gut microbiome imbalance negatively affecting immunological aspects. There is a link between ulcerative colitis and the oral microbiome. The changes of oral microbiome are found at many levels, from gently dysbiotic composition to the presence of the main periodontal microbes. The analysis of oral microbiome can be a part of personalized medicine due to the fact that it is a potential biomarker. Patients with ulcerative colitis may manifest dental symptoms/problems, such as periodontitis (strongly related to the red-complex pathogens-Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, and bacteria belonging to the other complexes, such as Fusobacterium nucleatum and Aggregatibacter actinomycetecomitans), dental caries, oral ulcerations, leukoplakia, halitosis, and others. Notably, the DMFT (Decayed, Missing, Filled Teeth) index is higher in these patients compared to healthy subjects. According to some data, oral lichen planus (which is a disease with an immunological background) can also be observed in ulcerative colitis patients. It seems that deep understanding of ulcerative colitis in association with oral microbiome, immunology, and dental manifestations may be crucial to provide complex treatment from a dental point of view.

Microbiota transplant therapy (MTT) is an emerging treatment for ulcerative colitis (UC). One proposed mechanism for the benefit of MTT is through engraftment of donor microbiota; however, engraftment kinetics are unknown. We identified SourceTracker as an efficient method both to determine engraftment and for the kinetic study of engrafting donor taxa to aid in determining the mechanism of how this therapy may treat UC.

Ulcerative colitis patients received either encapsulated (drug name MTP-101C) or placebo capsules daily for 8 weeks followed by a 4-week washout period. Amplicon sequence data from donors and patients were analyzed using the Bayesian algorithm SourceTracker.

Twenty-seven patients were enrolled, 14 to placebo and 13 to MTT. Baseline Shannon and Chao1 indices negatively correlated with week 12 donor engraftment for patients treated with active drug capsules but not for placebo patients. SourceTracker engraftment positively correlated with the week 12 distance from donors measured using the Bray-Curtis similarity metric in treated patients but not with placebo. Engraftment at week 12 was significantly higher in the MTT group than in the placebo group. We identified engrafting taxa from donors in our patients and quantified the proportion of donor similarity or engraftment during weeks 1 through 8 (active treatment) and week 12, 4 weeks after the last dose.

SourceTracker can be used as a simple and reliable method to quantify donor microbial community engraftment and donor taxa contribution in patients with UC and other inflammatory conditions treated with MTT.

Microorganisms in the gut play a pivotal role in human health, influencing various pathophysiological processes. Certain microorganisms are particularly essential for maintaining intestinal homeostasis, reducing inflammation, supporting nervous system function, and regulating metabolic processes. Short-chain fatty acids (SCFAs) are a subset of fatty acids produced by the gut microbiota (GM) during the fermentation of indigestible polysaccharides. The interaction between GM and SCFAs is inherently bidirectional: the GM not only shapes SCFAs composition and metabolism but SCFAs also modulate microbiota's diversity, stability, growth, proliferation, and metabolism. Recent research has shown that GM and SCFAs communicate through various pathways, mainly involving mechanisms related to inflammation and immune responses, intestinal barrier function, the gut-brain axis, and metabolic regulation. An imbalance in GM and SCFA homeostasis can lead to the development of several chronic diseases, including inflammatory bowel disease, colorectal cancer, systemic lupus erythematosus, Alzheimer's disease, and type 2 diabetes mellitus. This review explores the synergistic interactions between GM and SCFAs, and how these interactions directly or indirectly influence the onset and progression of various diseases through the regulation of the mechanisms mentioned above.

The gut microbiota, as a complex ecosystem, can affect many physiological aspects of the host's diet, disease development, drug metabolism, and immune system regulation. Polysaccharides have various biological activities including antioxidant, anti-tumor, and regulating gut microbiota, etc. Polysaccharides cannot be degraded by human digestive enzymes. However, the interaction between gut microbiota and polysaccharides can lead to the degradation and utilization of polysaccharides. Disordered intestinal flora leads to diseases such as diabetes, hyperlipidemia, tumors, and diarrhea. Notably, polysaccharides can regulate the gut microbiota, promote the proliferation of probiotics and the SCFAs production, and thus improve the related-diseases and maintain body health. The relationship between polysaccharides and gut microbiota is gradually becoming clear. Nevertheless, the structure-function relationships between polysaccharides and gut microbiota still need further exploration. Hence, this paper systematically reviews the structure-function relationships between polysaccharides and gut microbiota from four aspects including molecular weight, glycosidic bonds, monosaccharide composition, and advanced structure. Moreover, this review outlines the effect of polysaccharides on gut microbiota metabolism and improves diseases by regulating gut microbiota. Furthermore, this article introduces the impact of gut microbiota on polysaccharide metabolism. The findings can provide the scientific basis for in-depth research on body health and reasonable diet.

The polymorphic microbiome is considered a new hallmark of cancer. Advances in High-Throughput Sequencing have fostered rapid developments in microbiome research. The interaction between cancer cells, immune cells, and microbiota is defined as the immuno-oncology microbiome (IOM) axis. Fungal microbes (the mycobiome), although representing only ∼ 0.1-1% of the microbiome, are a critical immunologically active component of the tumor microbiome. Accumulating evidence suggests a possible involvement of commensal and pathogenic fungi in cancer initiation, progression, and treatment responsiveness. The tumor-associated mycobiome mainly consists of the gut mycobiome, the oral mycobiome, and the intratumoral mycobiome. However, the role of fungi in cancer remains poorly understood, and the diversity and complexity of analytical methods make it challenging to access this field. This review aims to elucidate the causal and complicit roles of mycobiome in cancer development and progression while highlighting the issues that need to be addressed in executing such research. We systematically summarize the advantages and limitations of current fungal detection and analysis methods. We enumerate and integrate these recent findings into our current understanding of the tumor mycobiome, accompanied by the prospect of novel and exhilarating clinical implications.

Gut microbiome-targeted therapies (MTTs), including prebiotics, probiotics, synbiotics, and fecal microbiota transplantation (FMT), have been widely used in inflammatory bowel diseases (IBD), but the best MTTs has not yet been confirmed. We performed a network meta-analysis (NMA) to examine this in ulcerative colitis (UC) and Crohn's disease (CD).

We searched for randomized controlled trials (RCTs) on the efficacy and safety of MTTs as adjuvant therapies for IBD until December 10, 2023. Data were pooled using a random effects model, with efficacy reported as pooled relative risks with 95% CIs, and interventions ranked according to means of surfaces under cumulative ranking values.

Thirty-eight RCTs met the inclusion criteria. Firstly, we compared the efficacy of MTTs in IBD patients. Only FMT and probiotics were superior to placebo in all outcomes, but FMT ranked best in improving clinical response rate and clinical and endoscopic remission rate, and probiotics ranked second in reducing clinical relapse rate showed significant efficacy, while prebiotics ranked first showed nonsignificant efficacy. Subsequently, we conducted NMA for specific MTT formulations in UC and CD separately, which revealed that FMT, especially combined FMT via colonoscopy and enema, showed significant efficacy and was superior in improving clinical response and remission rate of active UC patients. As for endoscopic remission and clinical relapse, multistrain probiotics based on specific genera of Lactobacillus and Bifidobacterium showed significant efficacy and ranked best in UC. In CD, we found that no MTTs were significantly better than placebo, but synbiotics comprising Bifidobacterium and fructo-oligosaccharide/inulin mix and Saccharomyces ranked best in improving clinical remission and reducing clinical relapse, respectively. Moreover, FMT was safe in both UC and CD.

FMT and multistrain probiotics showed superior efficacy in UC. However, the efficacy of MTTs varies among different IBD subtypes and disease stages; thus, the personalized treatment strategies of MTTs are necessary.

A growing number of studies have highlighted the significance of human gut microbiota (GM) as a potential target for osteoporosis. In this review, we discuss the effect of GM to bone metabolism focusing on two aspects: the local alterations of the human gut permeability that modify how the GM interact with the gut-bone axis (e.g., intestinal leakage, nutrient absorption), and the alterations of the GM itself (e.g., changes in microbiota metabolites, immune secretion, hormones) that modify the events of the gut-bone axis. We then classify these changes as possible therapeutic targets of bone metabolism and highlight some associated promising microbiome-based therapies. We also extend our discussions into combinatorial treatments that incorporate conservative treatments, such as exercise. We anticipate our review can provide an overview of the current pathophysiological and therapeutic paradigms of the gut-bone axis, as well as the prospects of ongoing clinical trials for readers to gain further insights into better microbiome-based treatments to osteoporosis and other bone-degenerative diseases. The translational potential of this article: This paper reviewed the potential links between gut microbiota and osteoporosis, as well as the prospective therapeutic avenues targeting gut microbiota for osteoporosis management, presenting a thorough and comprehensive literature review.

Pouchitis is a major complication after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis in children (UCc). In this study, we investigated whether the oral administration of Clostridium butyricum MIYAIRI 588 (CBM) can reduce the incidence of pouchitis after IPAA in UCc.

We reviewed the data for pediatric patients with UC, who underwent IPAA in Mie University Hospital between 2004 and 2022. Data on the presence and type of postoperative probiotic medication and the timing of probiotic initiation, as well as clinical variables, were collected from the patients' medical records.

During the study period, 55 children with UC underwent radical surgery. During the first 5 years after ileostomy closure, 23 (41.8%) patients suffered at least one pouchitis episode. The incidence of acute pouchitis was significantly lower in the CBM group than in the non-CBM group (CBM vs. non-CBM: 10.5% vs. 58.3%, p < 0.01). Furthermore, even among patients who had been taking any probiotics postoperatively, the CBM group had a significantly lower incidence of both acute and chronic pouchitis than the 'other probiotics' group (p < 0.01).

Oral CBM administration after ileostomy closure may be effective in preventing postoperative pouchitis.

Microbiota-derived toxins indoxyl sulfate and hippuric acid were previously reported to be associated with altered pharmacokinetics of the immunosuppressant tacrolimus in liver transplant recipients, and ABC transporter proteins are likely to be involved in the transport of such substances, but the in vivo role has not been elucidated. The aim of this study was to assess the retention of indoxyl sulfate and hippuric acid in the plasma of liver transplantation subjects carrying different genotypes of ABCB1 and ABCC2 (changes in transporter activity due to genetic variation), and to explore whether genetic variation is involved in altering the relationship between microbe-derived toxins and tacrolimus pharmacokinetics.

Liver transplantation subjects treated with the immunosuppressive regimen tacrolimus, corticosteroids, and mycophyolate mofetil were included and divided into normal renal function group and chronic kidney disease group. The plasma concentrations of indoxyl sulfate and hippuric acid in two groups of liver transplantation subjects carrying different genotypes of ABCB1 and ABCC2 were compared. For genotype carriers with significant differences, the Pearson Correlation Coefficient method was further used to investigate the correlation between plasma indoxyl sulfate level and tacrolimus dose-corrected trough concentration in patients with different renal function status.

Carriers of the rs717620-24T variant exhibited high plasma indoxyl sulfate retention in patients with normal renal function, and furthermore, chronic kidney disease patients and patients with normal renal function exhibited indoxyl sulfate and tacrolimus in the ABCC2 normal function (β = -0.740, p = 0.020) and reduced function groups (β = -0.526, p = 0.005), respectively, showing a strong correlation with tacrolimus.

ABCC2 may be one of the pathways by which tacrolimus pharmacokinetics is altered by indoxyl sulfate.

Ulcerative colitis (UC) is an idiopathic inflammatory bowel disease, and the range of current clinical treatments is not ideal. We previously found that polysaccharide of Atractylodes macrocephala Koidz (PAMK) is beneficial in DSS-induced colitis, and we aimed to investigate the underlying mechanisms in this study.

PAMK was used to treat DSS-induced colitis in mice, 16S rRNA sequencing analysis was used to detect changes in the intestinal microbiota, targeted metabolomics analysis was used to determine the content of tryptophan-metabolizing bacteria, and western blotting was used to determine aryl hydrocarbon receptor (AhR) and pregnane X receptor (PXR) levels. Furthermore, antibiotic-mediated depletion of gut microbiota and faecal microbiota transplantation were performed to assess the role of the gut microbiota in PAMK alleviation of colitis.

PAMK treatment relieved intestinal microbiota dysbiosis in mice with colitis, contributed to the proliferation of tryptophan-metabolizing bacteria, and increased the levels of tryptophan metabolites, resulting in a significant increase in the nuclear translocation of PXR and expression of PXR and its target genes, but not AhR. The gut microbiota is important in PAMK treatment of colitis, including in the alleviation of symptoms, inhibition of inflammation, maintenance of the integrity of the intestinal barrier, and the regulation of the Th17/Treg cell balance.

Based on our findings, we elucidate a novel mechanism by which PAMK alleviates DSS-induced colitis and thus provides evidence to support the potential development of PAMK as a new clinical drug against UC.

The homeostasis of the microbiota is essential for human health. In particular, the gut microbiota plays a critical role in the regulation of the immune system. Thus, faecal microbiota transplantation (FMT), a technology that has rapidly developed in the last decade, has specifically been utilised for the treatment of intestinal inflammation and has recently been found to be able to treat tumours in combination with immunotherapy. FMT has become a breakthrough in enhancing the response rate to immunotherapy in cancer patients by altering the composition of the patient's gut microbiota. This review discusses the mechanisms of faecal microorganism effects on tumour development, drug treatment efficacy, and adverse effects and describes the recent clinical research trials on FMT. Moreover, the factors influencing the efficacy and safety of FMT are described. We summarise the possibilities of faecal transplantation in the treatment of tumours and its complications and propose directions to explore the development of FMT.

Chronic apical periodontitis (CAP) has been linked to the development of atherosclerosis, although the underlying mechanisms remain unclear. This study aimed to investigate the role of gut microbiota disruption in CAP-induced atherosclerosis development, focusing on trimethylamine N-oxide (TMAO)-related metabolites.

The study utilized fecal microbiota transplantation (FMT) to transfer gut microbiota from mice with CAP to healthy mice. Atherosclerosis development was assessed by analyzing lesions in the aortic arch and aortic root. Serum lipid and inflammatory factor levels were measured. Composition and diversity of gut microbiota were analyzed using targeted metabolomics, with a focus on the ratio of Firmicutes to Bacteroidetes. The expression of hepatic flavin-containing monooxygenase 3 (FMO3) and serum TMAO levels were also evaluated.

Mice receiving gut microbiota from CAP mice showed increased atherosclerotic lesions compared to controls, without significant differences in serum lipid or inflammatory factor levels. Alterations in gut microbiota composition were observed, characterized by an increase in the Firmicutes to Bacteroidetes ratio. Peptostreptococcaceae abundance positively correlated with atherosclerosis severity, while Odoribacteraceae showed a negative correlation. No significant differences were found in hepatic FMO3 expression or serum TMAO levels.

The study confirms the role of gut microbiota disruption in CAP-mediated atherosclerosis development, independent of serum lipid or TMAO levels. Alterations in gut microbiota composition, particularly increased Firmicutes to Bacteroidetes ratio and specific bacterial families, were associated with atherosclerosis severity. These findings highlight the intricate interplay between gut microbiota and cardiovascular health in the context of CAP.

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disease with intricate pathogenesis, and clinical treatment is still not ideal. The imbalance of gut microbiota is associated with IBD progression. Various probiotics have been used as functional foods for the prevention and treatment of IBD, but the specific mechanism is still not fully understood. Lactobacillus johnsonii (L. johnsonii) is a potential anti-inflammatory bacterium, and compared to other probiotic Lactobacillus species, its colonization in the gut of colitis patients is significantly reduced. In this study, we first found that dietary L. johnsonii exerts strong anti-inflammatory and antioxidant effects in colitis mice, and this beneficial effect is directly related to its derived extracellular vesicles (LJ-EVs). Further experimental results indicate that LJ-EVs effectively prevented colitis symptoms and modulated gut microbiota and metabolic pathways. Meanwhile, we have studied for the first time the protective effect of LJ-EVs on the intestinal barrier from the perspective of reducing oxidative stress. We found that LJ-EVs can be directly taken up by intestinal epithelial cells and activate the Nrf2/HO-1 antioxidant signaling pathway, reducing endotoxin damage to cells and maintaining intestinal barrier homeostasis, which cascades to alleviate intestinal inflammation response. This study reveals the mechanism of L. johnsonii in treating colitis and provides a new approach for the development of oral LJ-EVs for the treatment of colitis.

Ulcerative colitis (UC) is a chronic colonic mucosal inflammation characterized by reduced gut microbial diversity. Patients with UC at pregnancy are prone to suffer from severe disease progression due to the changes of hormone and immune regulation. Fecal microbiota transplant (FMT) is a promising therapy for UC and recurrent Clostridium difficile infection (CDI). However, acute severe ulcerative colitis (ASUC) treatment especially in patients at pregnancy is clinically challenging. Herein, we report a 34-year-old pregnant woman who manifested with numerous bloody stools and markedly elevated serological inflammatory indicators and was diagnosed with ASUC and concurrent CDI. The use of intravenous injection steroids and anti-TNF-α therapy failed to improve her condition. Frozen encapsulated FMT therapy was finally performed to this patient with clearly improved symptoms and indications of safe delivery without UC flares or complications, and markedly increased diversity of the gut microbiota was also shown in this patient after FMT. This report firstly describes FMT as a safe salvage therapy for a pregnant patient with CDI and ASUC refractory to intravenous steroids and anti-TNF therapy.

Since 2015, an infliximab biosimilar, CT-P13, has been approved for commercial use in many countries, easing the economic burden borne by society and patients. Many clinical trials investigating CT-P13 for the treatment of IBD have been conducted and reported that it may be a substitute for infliximab. However, the differences between the efficacy of CT-P13 and infliximab-originator require further elucidation.

Data on the rates of clinical response, clinical remission, and mucosal healing of IBD were pooled for random-effects model meta-analysis using Stata MP 17. A total of 30 studies were included.

The pooled risk of clinical remission rate of patients with Crohn's disease and ulcerative colitis who were naïve to biologics at 08-14 weeks were 0.66 (95% CI, 0.58-0.75) and 0.48 (95% CI, 0.43-0.54), respectively, and at 100-104 weeks were 0.66 (95% CI, 0.49 to 0.84) and 0.71 (95% CI, 0.62 to 0.79) respectively. The pooled risk of clinical remission rate of patients with Crohn's disease and ulcerative colitis who were transitioned from the original agent at 24-32 weeks were 0.84 (95% CI, 0.77-0.92) and 0.78 (95% CI, 0.63-0.93), respectively, and at 48-54 weeks were 0.72 (95% CI, 0.62 to 0.82) and 0.78 (95% CI, 0.71 to 0.86) respectively. The pooled rates for mucosal healing in ulcerative colitis were 0.56 (95% CI: 0.46 to 0.67) at 08-14 weeks, and 0.64 (95% CI: 0.42 to 0.85) at 48-54 weeks. RCT studies showed no significant change in efficacy after switching, whether Crohn's disease or ulcerative colitis.

CT-P13 is effective in short and long-term periods. The application of CT-P13 for the management of IBD was promising.

The incidence of inflammatory bowel disease (IBD) has been increasing year by year in recent years. Flavonoids are the main components of mulberry leaves exerting anti-inflammatory effects and have potential applications in drug screening for IBD treatment. Enzymatic hydrolysis can enhance the bioavailability and activity of flavonoid glycosides. No relevant reports on the potentiation of mulberry leaf flavonoids (MLF) after deglycosylation have been retrieved.

An enzymatic method was used to prepare enzymatic hydrolysates of MLF (EMLF). The protective effect of EMLF on zebrafish with IBD was evaluated by observing zebrafish intestinal length and width, intestinal histopathological morphology, as well as neutrophil and goblet expression. Network pharmacology and metabolomics were performed to explore the mechanism of action of EMLF against IBD. Finally, the mechanism of EMLF against IBD was validated using Western Blot and real-time quantitative polymerase chain reaction (RT-qPCR).

The EMLF was successfully prepared by hydrolyzing MLF with snailase for the first time, and the anti-inflammatory effect of EMLF was clarified to be superior to that of MLF in IBD zebrafish. The network pharmacology and metabolomics studies showed that the mechanism of EMLF for IBD may be related to regulation of purine metabolic pathway. The expression levels of adenosine deaminase (ADA), critical targets in purine metabolism, were significantly down-regulated, while the expression of adenine phosphoribosyltransferase (APRT) and xanthine dehydrogenase (XDH) was significantly increased when compared with the TNBS group.

The results suggested that enzymatic deglycosylation is an effective measure to enhance the anti-inflammatory activity of MLF, which provides referable ideas and methods for the deep processing and utilization of natural drug resources.

Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory disease characterized by recurrent episodes and difficult-to-cure symptoms. Although the pathogenesis of IBD is closely related to host genetic susceptibility, intestinal microbiota, environmental factors, and immune responses, leading to mucosal damage and increased intestinal permeability. Intestinal mucosal injury in IBD patients causes pathogenic bacteria and pathogenic factors to invade the intestine, leading to disturb the structure and metabolic products of intestinal flora. Researchers have found that probiotics, as live microbial agents, can effectively inhibit the growth of pathogenic bacteria, regulate intestinal flora, optimize intestinal microecology, restore intestinal homeostasis, and promote intestinal mucosal repairing. During the oral delivery process, probiotics are susceptible to adverse physiological factors, leading to reduced bioavailability. Additionally, the oxidative stress microenvironment induced by intestinal mucosal damage makes it difficult for probiotics to colonize the intestinal tract of IBD patients, thereby affecting their probiotic effect. This research mainly introduces and reviews the advantages and disadvantages of probiotics and their protective strategies in the treatment of IBD, and prospects the future development trends of probiotics and their protective strategies. Probiotics can effectively inhibit the growth of harmful microorganisms, regulate the structure of the intestinal microbiota, and promote mucosal repairing, thereby reducing immune stress and alleviating intestinal inflammation, providing a new perspective for the treatment of IBD. The development of single-cell encapsulation technology not only effectively maintaining the biological activity of probiotics during oral delivery, but also endowing probiotics with additional biological functions naturally achieved through surface programming, which has multiple benefits for intestinal health.

Numerous studies have highlighted the close association between gut microbiota and the development of ulcerative colitis (UC), yet research on whether immune cells mediate this process remains scarce. This study utilizes various Mendelian randomization (MR) methods to investigate the causal relationship between gut microbiota and UC, further exploring the mediating role of immune cells in this process.

Genome-wide association study (GWAS) summary statistics for 473 gut microbiota, 731 immune cell phenotypes, and UC were obtained from the GWAS catalog database. Single nucleotide polymorphisms (SNP) were used as instrumental variables (IV) to validate the causal relationship between gut microbiota and UC through two-sample MR and Bayesian weighted MR (BWMR), and reverse MR was employed to explore the presence of reverse causal effects. Two-step MR was applied to identify immune cell mediators and evaluate their mediation effects.

The study revealed a causal relationship between 20 gut microbiota and UC, with 14 microbiota acting as protective factors for UC and 6 as risk factors. Mediation MR identified 26 immune cell mediators, among which the association between CD11b on Mo MDSC and Bifidobacterium bifidum (B. bifidum) was most significant (p = 0.0017, OR = 1.4540, 95% CI: 1.1504-1.8378). Mediation MR analysis indicated that the mediation effect of CD11b on Mo MDSC between B. bifidum and UC was -0.0385, with a mediation effect ratio of 16.67%.

There is a clear causal relationship between certain gut microbiota and UC, and CD11b on Mo MDSC is a significant mediator between B. bifidum and UC, providing new insights for the clinical treatment of UC.

The fungi of the human microbiota play important roles in the nutritional metabolism and immunological balance of the host. Recently, research has increasingly emphasised the role of fungi in modulating inflammation in intestinal diseases and maintaining health in this environment. It is therefore necessary to understand more clearly the interactions and mechanisms of the microbiota/pathogen/host relationship and the resulting inflammatory processes, as well as to offer new insights into the prevention, diagnosis and treatment of inflammatory bowel disease (IBD), colorectal cancer (CRC) and other intestinal pathologies. In this review, we comprehensively elucidate the fungal-associated pathogenic mechanisms of intestinal inflammation in IBD and related CRC, with an emphasis on three main aspects: the direct effects of fungi and their metabolites on the host, the indirect effects mediated by interactions with other intestinal microorganisms and the immune regulation of the host. Understanding these mechanisms will enable the development of innovative approaches based on the use of fungi from the resident human microbiota such as dietary interventions, fungal probiotics and faecal microbiota transplantation in the prevention, diagnosis and treatment of intestinal diseases.

The expanding applications of graphene oxide (GO) nanomaterials have attracted interest in understanding their potential adverse effects on embryonic and fetal development. Numerous studies have revealed the importance of the maternal gut microbiota in pregnancy. In this study, we established a mouse GO exposure model to evaluate embryo toxicity induced by intravenous administration of GO during pregnancy. We also explored the roles of gut microbiota and fecal metabolites using a fecal microbiota transplantation (FMT) intervention model. We found that administration of GO at doses up to 1.25 mg/kg caused embryo toxicity, characterized by significantly increased incidences of fetal resorption, stillbirths, and decreased birth weight. In pregnant mice with embryo toxicity, the richness of the maternal gut microbiota was dramatically decreased, and components of the microbial community were disturbed. FMT alleviated the decrease in birth weight by remodeling the gut microbiota, especially via upregulation of the Firmicutes/Bacteroidetes ratio. We subsequently used untargeted metabolomics to identify characteristic fecal metabolites associated with GO exposure. These metabolites were closely correlated with the phyla Actinobacteria, Proteobacteria, and Cyanobacteria. Our findings offer new insights into the embryo toxic effects of GO exposure during pregnancy; they emphasize the roles of gut microbiota-metabolite interactions in adverse pregnancy outcomes induced by GO or other external exposures, as demonstrated through FMT intervention.

The online version contains supplementary material available at 10.1007/s43188-024-00242-3.

To investigate the presence of dysbiosis in patients with naive bladder cancer.

Twelve male patients with non-invasive bladder cancer and twelve age-matched healthy males had midstream urine and tissue samples taken. A history of endourological interventions was determined as an exclusion criterion, ensuring that the study was designed solely with naïve participants. The bacterial 16s ribosomal RNA V3-V4 regions were used to examine urine and tissue samples. We compared the microbiota composition of the bladder cancer and control groups.

Escherichia Shigella (p < 0.001), Staphylococcus (p < 0.001), Delftia (p < 0.001), Acinetobacter (p < 0.001), Corynebacterium (p < 0.001), and Enhydrobacter (p < 0.001) were abundant in bladder cancer tissue samples. Escherichia Shigella (p < 0.001), Ureaplasma (p < 0.001), Lactobacillus (p = 0.005), Stenotrophomonas (p < 0.001), Streptococcus (p < 0.001), Corynebacterium (p < 0.001), and Prevotella (p = 0.039) were abundant in bladder cancer urine samples. Midstream urine has a sensitivity of 83% for detecting dysbiotic bacteria in cancer tissue.

Our research is the first microbiota study of bladder cancer done with naive patients who have never had an endourological intervention. Escherichia Shigella, Staphylococcus, Acinetobacter, Enhydrobacter, Delftia, Corynebacterium, and Pseudomonas were detected as dysbiotic bacteria in bladder cancer. The sensitivity of the midstream urine sample in detecting dysbiosis in tissue is 83%.

A clinical trial was conducted to evaluate the effect of fecal microbiota transplantation (FMT) on the canine chronic enteropathy clinical activity index (CCECAI), fecal consistency, and microbiome of dogs with tylosin-responsive enteropathy (TRE). The trial consisted of four phases: (1) screening with discontinuation of tylosin for 4 weeks, (2) inclusion with re-introduction of tylosin for 3-7 days, (3) treatment with FMT/placebo for 4 weeks, and (4) post-treatment with follow-up for 4 weeks after treatment cessation. The study found that the treatment efficacy of FMT (71.4%) was slightly higher than that of placebo (50%), but this difference was not statistically significant due to underpowering. The most abundant bacterial species detected in the fecal microbiomes of dogs with TRE before FMT or placebo treatment were Blautia hansenii, Ruminococcus gnavus, Escherichia coli, Clostridium dakarense, Clostridium perfringens, Bacteroides vulgatus, and Faecalimonas umbilicata. After FMT, the microbiomes exhibited increases in Clostridium dakarense, Clostridium paraputrificum, and Butyricicoccus pullicaecorum. The microbiome alpha diversity of TRE dogs was lower when on tylosin treatment compared to healthy dogs, but it increased after treatment in both the FMT and placebo groups. Comparisons with the stool donor showed that, on average, 30.4% of donor strains were engrafted in FMT recipients, with the most common strains being several Blautia sp., Ruminococcus gnavus, unclassified Lachnoclostridium, Collinsella intestinalis, and Fournierella massiliensis.

Previous research has demonstrated an association between gut microbiota and immune status with the development of several diseases. However, whether these factors contribute to polyps remains unclear. This study aims to use Mendelian randomization (MR) to investigate the causal relationship between gut microbiota and 4 types of polyps (nasal, gallbladder, colon, and gastric polyps), as well as to analyze the mediating role of immune traits.

This study utilized large-scale GWAS meta-analyses of gut microbiota (MiBioGen Consortium), 731 immune traits, and 4 types of polyps (one from the FinnGen Consortium and three from the NBDC Human Database). Univariate MR with the inverse variance weighted (IVW) estimation method was employed as the primary analytical approach. A two-step MR analysis was performed to identify potential mediating immune traits. Additionally, multivariable MR approach based on Bayesian model averaging (MR-BMA) was employed to further prioritize gut microbiota and immune traits associated with polyp development.

Based on IVW method in univariate MR analysis, we identified 39 gut microbial taxa and 135 immune traits significantly causally associated with at least one type of polyp. For nasal polyps, 13 microbial taxa and 61 immune traits were causally associated. After false discovery rate (FDR) correction, CD3 on Central Memory CD8+ T cells and CD3 on CD4 regulatory T cells remained significant. MR-BMA identified 4 gut microbial taxa and 4 immune traits as high priority. For gallbladder polyps, 9 microbial taxa and 30 immune traits were causally associated. MR-BMA identified 8 microbial taxa and 6 immune traits as higher importance. For colon polyps, 6 microbial taxa and 21 immune traits were causally associated. MR-BMA identified 4 microbial taxa and 3 immune traits as higher importance. For gastric polyps, 12 microbial taxa and 33 immune traits were causally associated. Actinobacteria remained significant after FDR correction, and MR-BMA identified 7 gut microbial taxa and 6 immune traits as high priority. We identified 16 causal pathways with mediator directions consistent with the direction of gut microbiome-polyp association. Of these, 6 pathways were associated with the mechanism of nasal polyps, 1 with gallbladder polyps, 2 with colon polyps, and 7 with gastric polyps.

Our findings shed light on the causal relationships between gut microbiota, immune traits, and polyp development, underscoring the crucial roles of gut microbiota and immune status in polypogenesis. Furthermore, these findings suggest potential applications in polyp prevention, early screening, and the development of effective strategies to reduce polyp risk.

Inflammatory bowel diseases (IBDs) are immune chronic diseases characterized by recurrent episodes, resulting in continuous intestinal barrier damage and intestinal microbiota dysbiosis. Safe strategies aimed at stabilizing and reducing IBDs recurrence have been vigorously pursued. Here, we constructed a recurrent intestinal injury Drosophila model and found that vitamin B12 (VB12), an essential co-factor for organism physiological functions, could effectively protect the intestine and reduce dextran sulfate sodium-induced intestinal barrier disruption. VB12 also alleviated microbial dysbiosis in the Drosophila model and inhibited the growth of gram-negative bacteria. We demonstrated that VB12 could mitigate intestinal damage by activating the hypoxia-inducible factor-1 signaling pathway in injured conditions, which was achieved by regulating the intestinal oxidation. In addition, we also validated the protective effect of VB12 in a murine acute colitis model. In summary, we offer new insights and implications for the potential supportive role of VB12 in the management of recurrent IBDs flare-ups.

Endemic fluorosis has gained increasing attention as a public health concern, and the escalating risk of colitis resulting from excessive fluoride intake calls for effective mitigation strategies. This study aimed to investigate the potential mechanisms underlying the alleviation of fluoride-induced colitis by Tea polysaccharides (TPS). Under conditions of excessive fluoride intake, significant changes were observed in the gut microbiota of rats, leading to aggravated colitis. However, the intervention of TPS exerted a notable alleviating effect on colitis symptoms. Antibiotic intervention and fecal microbiota transplantation (FMT) experiments provided evidence that TPS-mediated relief of fluoride-induced colitis is mediated through its effects on the gut microbiota. Furthermore, TPS supplementation was found to modulate the structure of gut microbiota, enhance the relative abundance of Limosilactobacillus vaginalis in the gut microbiota, and promote the expression of short-chain fatty acid (SCFAs) receptors in colonic tissue. Notably, L. vaginalis played a significant role in alleviating fluoride-induced colitis and facilitating the absorption of butyric acid in the rat colon. Subsequent butyric acid intervention experiments confirmed its remarkable alleviating effect on fluoride-induced colitis. Overall, these findings provide a potential preventive strategy for fluoride-induced colitis by TPS intervention, which is mediated by L. vaginalis and butyric acid.

Inflammatory bowel disease (IBD) is an incurable, chronic disorder of the gastrointestinal tract whose incidence increases every year. Scientific research constantly delivers new information about the disease and its multivariate, complex etiology. Nevertheless, full discovery and understanding of the complete mechanism of IBD pathogenesis still pose a significant challenge to today's science. Recent studies have unanimously confirmed the association of gut microbial dysbiosis with IBD and its contribution to the regulation of the inflammatory process. It transpires that the altered composition of pathogenic and commensal bacteria is not only characteristic of disturbed intestinal homeostasis in IBD, but also of viruses, parasites, and fungi, which are active in the intestine. The crucial function of the microbial metabolome in the human body is altered, which causes a wide range of effects on the host, thus providing a basis for the disease. On the other hand, human genomic and functional research has revealed more loci that play an essential role in gut homeostasis regulation, the immune response, and intestinal epithelial function. This review aims to organize and summarize the currently available knowledge concerning the role and interaction of crucial factors associated with IBD pathogenesis, notably, host genetic composition, intestinal microbiota and metabolome, and immune regulation.

The gut microbiome is involved in the pathogenesis of many diseases including polycystic ovarian syndrome (PCOS). Modulating the gut microbiome can lead to eubiosis and treatment of various metabolic conditions. However, there is no proper study assessing the delivery of microbial technology for the treatment of such conditions. The present study involves the development of guar gum-pectin-based solid self-nanoemulsifying drug delivery system (S-SNEDDS) containing curcumin (CCM) and fecal microbiota extract (FME) for the treatment of PCOS. The optimized S-SNEDDS containing FME and CCM was prepared by dissolving CCM (25 mg) in an isotropic mixture consisting of Labrafil M 1944 CS, Transcutol P, and Tween-80 and solidified using lactose monohydrate, aerosil-200, guar gum, and pectin (colon-targeted CCM solid self-nanoemulsifying drug delivery system [CCM-CT-S-SNEDDS]). Pharmacokinetic and pharmacodynamic evaluation was carried out on letrozole-induced female Wistar rats. The results of pharmacokinetic studies indicated about 13.11 and 23.48-fold increase in AUC of CCM-loaded colon-targeted S-SNEDDS without FME (CCM-CT-S-SNEDDS (WFME)) and CCM-loaded colon-targeted S-SNEDDS with FME [(CCM-CT-S-SNEDDS (FME)) as compared to unprocessed CCM. The pharmacodynamic study indicated excellent recovery/reversal in the rats treated with CCM-CT-S-SNEDDS low and high dose containing FME (group 13 and group 14) in a dose-dependent manner. The developed formulation showcasing its improved bioavailability, targeted action, and therapeutic activity in ameliorating PCOS can be utilized as an adjuvant therapy for developing a dosage form, scale-up, and technology transfer.

The intestinal mucus barrier is an important line of defense against gut pathogens. Damage to this barrier brings bacteria into close contact with the epithelium, leading to intestinal inflammation. Therefore, its restoration is a promising strategy for alleviating intestinal inflammation. This study showed that Abelmoschus manihot polysaccharide (AMP) fortifies the intestinal mucus barrier by increasing mucus production, which plays a crucial role in the AMP-mediated amelioration of colitis. IL-10-deficient mouse models demonstrated that the effect of AMP on mucus production is dependent on IL-10. Moreover, bacterial depletion and replenishment confirmed that the effects of AMP on IL-10 secretion and mucus production were mediated by Akkermansia muciniphila. These findings suggest that plant polysaccharides fortify the intestinal mucus barrier by maintaining homeostasis in the gut microbiota. This demonstrates that targeting mucus barrier is a promising strategy for treating intestinal inflammation.

Dysbiosis may be a key driver of systemic inflammation, which increases the risk of non-AIDS events in people living with HIV (PLWH). Modulation of the microbiome to reverse this dysbiosis may be a novel approach to decrease inflammation and therefore morbidity and mortality in PLWH.

Fecal microbiota transplantation (FMT), probiotics, prebiotics, synbiotics, postbiotics, and dietary modifications have the potential to modulate the microbiome. These interventions have been well tolerated in clinical trials to date. However, these interventions have not resulted in consistent or lasting changes to the microbiome or consistent changes in biomarkers of intestinal permeability, microbial translocation, inflammation, immune activation, or CD4 + T cell counts. Sustained engraftment may require prebiotics and/or dietary modifications added to either probiotics or FMT.

Adequately powered randomized controlled trials are needed to elucidate whether microbiome modulation can be achieved and impact systemic inflammation in PLWH.

There are complex interactions between the gut and the brain. With increasing research on the relationship between gut microbiota and brain function, accumulated clinical and preclinical evidence suggests that gut microbiota is intimately involved in the pathogenesis of neurodegenerative diseases (NDs). Increasingly studies are beginning to focus on the association between gut microbiota and central nervous system (CNS) degenerative pathologies to find potential therapies for these refractory diseases. In this review, we summarize the changes in the gut microbiota in Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis and contribute to our understanding of the function of the gut microbiota in NDs and its possible involvement in the pathogenesis. We subsequently discuss therapeutic approaches targeting gut microbial abnormalities in these diseases, including antibiotics, diet, probiotics, and fecal microbiota transplantation (FMT). Furthermore, we summarize some completed and ongoing clinical trials of interventions with gut microbes for NDs, which may provide new ideas for studying NDs.