[Influence of different fecal microbiota transplantation cycles on the recovery of intestinal microbiota in the antibiotic cocktail-pretreated mice].

OBJECTIVE: To explore the effects of different transplantation frequencies and time of fecal microbiota transplantation on mice. METHODS: Twenty-four C57BL/6J mice were randomly divided into control group, fecal microbiota transplantation group 1(FMT1), fecal microbiota transplantation group 2(FMT2), and fecal microbiota transplantation group 3(FMT3). The control group was used as the donor of fecal microbiota transplantation, and the FMT1, FMT2, and FMT3 groups were intervened with mixed antibiotics(200 µL/d) for 2 weeks, and received fecal bacterial suspension(200 µL/d). The transplantation time of the FMT1 group frequency was 1 time/d for 1 weeks, the FMT2 group was 1 time/d for 2 weeks, and the FMT3 group was 3 times/week for 2 weeks. At the end of the experiment, the feces of the mice were collected to analyze the gut microbiota. RESULTS: Compared with the control group, there were more independent Amplicon Sequence Variants in the intestinal microbiota of mice in FMT1 group, FMT2 group and FMT3 group, and the ACE index and Chao1 index were significantly reduced(P<0.05). Beta diversity showed differences between fecal microbiota transplantation and control groups, with FMT2 and control groups being the closest. At the phylum level, there were two species in FMT1 group and one species in FMT3 group showed statistically significant differences compared with control group(P<0.05). However, there was no significant difference between the FMT2 group and the control group. At the genus level, there were 6 species in the FMT1 with statistically significant differences from the control group(P<0.05), and 2 species in the FMT2, 5 species in the FMT3 respectively. Among which FMT2 group has the least number of species that differed from the control group, suggesting that the compitsition of its intestinal microbiota is closet to that of the control group. CONCLUSION: Fecal bacteria transplantation helps to restore the intestinal microbiota structure of mice cleaned by antibiotics, and different transplantation frequencies and transplantation times have different recovery effects on the intestinal microbiota of mice pretreated with antibiotics, and the fecal bacteria transplantation effect is better with 1 time/d lasting 2 weeks.

Gut Microbial Metabolome and Dysbiosis in Neurodegenerative Diseases: Psychobiotics and Fecal Microbiota Transplantation as a Therapeutic Approach-A Comprehensive Narrative Review.

The comprehensive narrative review conducted in this study delves into the mechanisms of communication and action at the molecular level in the human organism. The review addresses the complex mechanism involved in the microbiota-gut-brain axis as well as the implications of alterations in the microbial composition of patients with neurodegenerative diseases. The pathophysiology of neurodegenerative diseases with neuronal loss or death is analyzed, as well as the mechanisms of action of the main metabolites involved in the bidirectional communication through the microbiota-gut-brain axis. In addition, interventions targeting gut microbiota restructuring through fecal microbiota transplantation and the use of psychobiotics-pre- and pro-biotics-are evaluated as an opportunity to reduce the symptomatology associated with neurodegeneration in these pathologies. This review provides valuable information and facilitates a better understanding of the neurobiological mechanisms to be addressed in the treatment of neurodegenerative diseases.

Efficacy and safety of fecal microbiota transplantation in the treatment of ulcerative colitis: a systematic review and meta-analysis.

To explore the efficacy and safety of fecal microbiota transplantation (FMT) as a treatment approach for ulcerative colitis (UC), a comprehensive systematic review and meta-analysis of randomized controlled trials was conducted. To collect and evaluate randomized controlled trials of high quality on FMT for UC, we searched a number of databases, including PubMed, Web of Science, Cochrane, Embase, and Medline, for studies published between the establishment of the databases and March 2023. We conducted a meta-analysis of the studies using Review Manager software (version 5.4.1) to determine the differences in rates of remission and adverse reactions between the FMT group and the control group, utilizing the risk ratio (RR) and 95% confidence interval (CI) to combine our findings. A total of 13 randomized controlled trials (RCTs) on the efficacy of FMT in patients with UC were included in the study, in which 580 patients participated, including 293 patients treated with FMT and 287 control subjects. Meta-analysis revealed that clinical remission was significantly better in the FMT group than in the control group [RR = 1.73; 95% CI = (1.41, 2.12); P < 0.00001]; endoscopic remission was significantly better in the FMT group than in the control group [RR = 1.74; 95% CI = (1.24, 2.44); P = 0.001]. Additionally, there were no significant differences in the incidence of adverse reactions between the two groups [RR = 1.00; 95% CI = (0.86, 1.15); P = 0.96]. Fecal microbiota transplantation has shown potential as a therapeutic intervention for inducing clinical remission in ulcerative colitis UC; nevertheless, the attainment of endoscopic remission and the maintenance of long-term remission continue to present challenges. Safety concerns persist throughout the treatment process, necessitating the implementation of measures to augment both safety and success rates.

The Impacts of Fecal Microbiota Transplantation from Same Sex on the Symptoms of Ulcerative Colitis Patients.

We aimed to compare the clinical efficacy of fecal microbiota transplantation (FMT) from the same sex on ulcerative colitis (UC) patients. A total of 272 UC patients were selected in the prospective clinical study, which incorporated four distinct groups, each comprising male and female patients, who were either receiving FMT or placebo, respectively. FMT was performed by sending the gut microbiota of healthy female or male adolescents to the same gender patients via gastroscope three times (one time/three weeks), and a placebo was used with an equal volume of saline. Abdominal pain, diarrhea, thick bloody stool, intestinal mucosal lesion, and Mayo scores were measured. Self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were evaluated. The changes of intestinal flora were detected by the 16S rRNA sequencing. FMT reduced the scores of diarrhea, abdominal pain, mucosal lesion, and Mayo, SAS, and SDS in UC patients compared to the placebo group (p < 0.05). Clostridiales and Desulfovibrionaceae were dominant in gut microbiota from male patients and were reduced after FMT. Meanwhile, the abundance of Prevotella, Lactobacillus, and Bifidobacterium was increased in the male group. Female patients had a higher abundance of Escherichia-Shigella, Desulfovibrionaceae, and Staphylococcaceae before FMT, and it was reduced after FMT. Meanwhile, the abundance of Porphyromonadaceae, Prevotella, Lactobacillus, and Bifidobacterium was increased in the female group. There were no significant changes for the species in the corresponding placebo groups. FMT improved the UC symptoms of male and female patients, which may be associated with different gut microbiota changes.

Phage-microbe dynamics after sterile faecal filtrate transplantation in individuals with metabolic syndrome: a double-blind, randomised, placebo-controlled clinical trial assessing efficacy and safety.

Bacteriophages (phages) are bacterial viruses that have been shown to shape microbial communities. Previous studies have shown that faecal virome transplantation can decrease weight gain and normalize blood glucose tolerance in diet-induced obese mice. Therefore, we performed a double-blind, randomised, placebo-controlled pilot study in which 24 individuals with metabolic syndrome were randomised to a faecal filtrate transplantation (FFT) from a lean healthy donor (n = 12) or placebo (n = 12). The primary outcome, change in glucose metabolism, and secondary outcomes, safety and longitudinal changes within the intestinal bacteriome and phageome, were assessed from baseline up to 28 days. All 24 included subjects completed the study and are included in the analyses. While the overall changes in glucose metabolism are not significantly different between both groups, the FFT is well-tolerated and without any serious adverse events. The phage virion composition is significantly altered two days after FFT as compared to placebo, which coincides with more virulent phage-microbe interactions. In conclusion, we provide evidence that gut phages can be safely administered to transiently alter the gut microbiota of recipients.

Fecal microbiota transplantation inhibited neuroinflammation of traumatic brain injury in mice via regulating the gut-brain axis.

Introduction: Recent studies have highlighted the vital role of gut microbiota in traumatic brain injury (TBI). Fecal microbiota transplantation (FMT) is an effective means of regulating the microbiota-gut-brain axis, while the beneficial effect and potential mechanisms of FMT against TBI remain unclear. Here, we elucidated the anti-neuroinflammatory effect and possible mechanism of FMT against TBI in mice via regulating the microbiota-gut-brain axis. Methods: The TBI mouse model was established by heavy object falling impact and then treated with FMT. The neurological deficits, neuropathological change, synaptic damage, microglia activation, and neuroinflammatory cytokine production were assessed, and the intestinal pathological change and gut microbiota composition were also evaluated. Moreover, the population of Treg cells in the spleen was measured. Results: Our results showed that FMT treatment significantly alleviated neurological deficits and neuropathological changes and improved synaptic damage by increasing the levels of the synaptic plasticity-related protein such as postsynaptic density protein 95 (PSD-95) and synapsin I in the TBI mice model. Moreover, FMT could inhibit the activation of microglia and reduce the production of the inflammatory cytokine TNF-α, alleviating the inflammatory response of TBI mice. Meanwhile, FMT treatment could attenuate intestinal histopathologic changes and gut microbiota dysbiosis and increase the Treg cell population in TBI mice. Conclusion: These findings elucidated that FMT treatment effectively suppressed the TBI-induced neuroinflammation via regulating the gut microbiota-gut-brain axis, and its mechanism was involved in the regulation of peripheral immune cells, which implied a novel strategy against TBI.

CE: Current and Emerging Applications of Fecal Microbiota Transplantation.

ABSTRACT: Fecal microbiota transplantation (FMT) is a life-changing treatment for people with recurrent Clostridioides difficile infection (rCDI). Frequently acquired in the hospital, CDI can cause serious gastrointestinal symptoms, including persistent watery diarrhea, abdominal pain, and severe dehydration. Antibiotics, the primary treatment, can unfortunately disrupt the gut microbiome and lead to antimicrobial resistance. FMT involves introducing stool from a healthy donor into the affected recipient to strengthen their compromised microbiome. Individuals receiving this treatment have reported remarkable improvement in clinical outcomes and quality of life. In addition to a discussion of rCDI within the context of the gastrointestinal microbiome, this article provides an overview of the FMT procedure, discusses nursing management of individuals undergoing FMT, and highlights emerging applications beyond rCDI. A case scenario is also provided to illustrate a typical trajectory for a patient undergoing FMT.

Protocol for a double-blinded randomised controlled trial to assess the effect of faecal microbiota transplantations on thyroid reserve in patients with subclinical autoimmune hypothyroidism in the Netherlands: the IMITHOT trial.

BACKGROUND: Hashimoto's thyroiditis (HT) is a common endocrine autoimmune disease affecting roughly 5% of the general population and involves life-long treatment with levothyroxine, as no curative treatment yet exists. Over the past decade, the crosstalk between gut microbiota and the host immune system has been well-recognised, identifying the gut microbiome as an important factor in host health and disease, including susceptibility to autoimmune diseases. Previous observational studies yielded a link between disruption of the gut microbiome composition and HT. This is the first study that investigates the potential of restoring a disrupted gut microbiome with faecal microbiota transplantations (FMTs) to halt disease progression and dampen autoimmunity. METHODS AND ANALYSIS: The IMITHOT trial is a randomised, double-blinded, placebo-controlled study evaluating either autologous or allogenic FMTs in medication-naïve patients with subclinical autoimmune hypothyroidism. In total, 34 patients will be enrolled to receive either three allogenic or autologous FMTs. FMT will be made of fresh stool and directly administered into the duodenum. Patients will be evaluated at baseline before the first FMT is administered and at 6, 12 and 24 months post-intervention to assess efficacy and adverse events. The primary outcome measure will be the net incremental increase (incremental area under the curve) on thyrotropin-stimulated free thyroxine and free triiodothyronine release at 6 and 12 months compared with baseline. Results will be disseminated via peer-reviewed journals and international conferences. The recruitment of the first patient and donor occurred on 18 December 2019. ETHICS AND DISSEMINATION: Ethics approval was obtained from the hospital Ethics Committee (Medical Ethics Committee) at Amsterdam University Medical Center. The trial's outcomes offer high-quality evidence that aids in unveiling distinct patterns within the gut microbiota potentially associated with improved thyroid function. Consequently, this may open avenues for the future clinical applications of microbial-targeted therapy in individuals at risk of developing overt HT. TRIAL REGISTRATION NUMBER: NL7931.

Fecal microbiota transplantation alleviates experimental colitis through the Toll-like receptor 4 signaling pathway.

BACKGROUND: Fecal microbiota transplantation (FMT) has shown promising therapeutic effects on mice with experimental colitis and patients with ulcerative colitis (UC). FMT modulates the Toll-like receptor 4 (TLR4) signaling pathway to treat some other diseases. However, it remains unknown whether this modulation is also involved in the treatment of UC. AIM: To clarify the necessity of TLR4 signaling pathway in FMT on dextran sodium sulphate (DSS)-induced mice and explain the mechanism of FMT on UC, through association analysis of gut microbiota with colon transcriptome in mice. METHODS: A mouse colitis model was constructed with wild-type (WT) and TLR4-knockout (KO) mice. Fecal microbiota was transplanted by gavage. Colon inflammation severity was measured by disease activity index (DAI) scoring and hematoxylin and eosin staining. Gut microbiota structure was analyzed through 16S ribosomal RNA sequencing. Gene expression in the mouse colon was obtained by transcriptome sequencing. RESULTS: The KO (DSS + Water) and KO (DSS + FMT) groups displayed indistinguishable body weight loss, colon length, DAI score, and histology score, which showed that FMT could not inhibit the disease in KO mice. In mice treated with FMT, the relative abundance of Akkermansia decreased, and Lactobacillus became dominant. In particular, compared with those in WT mice, the scores of DAI and colon histology were clearly decreased in the KO-DSS group. Microbiota structure showed a significant difference between KO and WT mice. Akkermansia were the dominant genus in healthy KO mice. The ineffectiveness of FMT in KO mice was related to the decreased abundance of Akkermansia. Gene Ontology enrichment analysis showed that differentially expressed genes between each group were mainly involved in cytoplasmic translation and cellular response to DNA damage stimulus. The top nine genes correlating with Akkermansia included Aqp4, Clca4a, Dpm3, Fau, Mcrip1, Meis3, Nupr1 L, Pank3, and Rps13 (|R| > 0.9, P < 0.01). CONCLUSION: FMT may ameliorate DSS-induced colitis by regulating the TLR4 signaling pathway. TLR4 modulates the composition of gut microbiota and the expression of related genes to ameliorate colitis and maintain the stability of the intestinal environment. Akkermansia bear great therapeutic potential for colitis.

Psychobiotics and fecal microbial transplantation for autism and attention-deficit/hyperactivity disorder: microbiome modulation and therapeutic mechanisms.

Dysbiosis of the gut microbiome is thought to be the developmental origins of the host's health and disease through the microbiota-gut-brain (MGB) axis: such as immune-mediated, metabolic, neurodegenerative, and neurodevelopmental diseases. Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are common neurodevelopmental disorders, and growing evidence indicates the contribution of the gut microbiome changes and imbalances to these conditions, pointing to the importance of considering the MGB axis in their treatment. This review summarizes the general knowledge of gut microbial colonization and development in early life and its role in the pathogenesis of ASD/ADHD, highlighting a promising therapeutic approach for ASD/ADHD through modulation of the gut microbiome using psychobiotics (probiotics that positively affect neurological function and can be applied for the treatment of psychiatric diseases) and fecal microbial transplantation (FMT).

A Comparison of Methods of Gut Microbiota Transplantation for Preclinical Studies.

The experimental details reported in preclinical fecal microbiota transplantation (FMT) protocols are highly inconsistent, variable, and/or incomplete. We therefore evaluated FMT from a human donor to antibiotic-induced microbial-depleted mice by exploring the effects of six techniques based on antibiotic (AB) or antibiotic + antimycotic (AB + T) gut decontamination, different administration routes, and different dosing intervals on the gut microbial population, assessed using 16S and 18S sequencing. In addition, we explored the effectiveness of FMT in terms of inflammation, physiological, and behavioral outcomes. Our results showed that intrarectal FMT at low dosing intervals better preserved the donor's gut bacterial community at genus level. Furthermore, we showed a lower abundance of several genera of fungi in animals treated with AB + T. In addition, we observed that AB + T gut decontamination followed by per os FMT, once every 3 days, affected behavioral parameters when compared to other FMT techniques. Accordingly, the same FMT groups that showed an association with some of the behavioral tests were also related to specific gut fungal genera, suggesting a possible mediation. Our findings may be useful for optimizing the practice of FMT and also in terms of donor microbiota preservation. This information may help to improve the reproducibility and reliability of FMT studies.

How Would You Manage This Patient With Clostridioides difficile Infection? : Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

The Infectious Diseases Society of America/Society for Healthcare Epidemiology of America and the American College of Gastroenterology recently released updated guidelines on management of patients with Clostridioides difficile infection. Although these 2 guidelines generally agree, there are a few important differences in their advice to clinicians. In these rounds, 2 experts, an infectious diseases specialist and a gastroenterologist, discuss antibiotic treatment options for nonsevere disease, the role of fecal microbiota transplantation for fulminant disease, and the use of bezlotoxumab to prevent recurrence in the context of Ms. C, a 48-year-old woman with fulminant C difficile infection.

Recipient-independent, high-accuracy FMT-response prediction and optimization in mice and humans.

BACKGROUND: Some microbiota compositions are associated with negative outcomes, including among others, obesity, allergies, and the failure to respond to treatment. Microbiota manipulation or supplementation can restore a community associated with a healthy condition. Such interventions are typically probiotics or fecal microbiota transplantation (FMT). FMT donor selection is currently based on donor phenotype, rather than the anticipated microbiota composition in the recipient and associated health benefits. However, the donor and post-transplant recipient conditions differ drastically. We here propose an algorithm to identify ideal donors and predict the expected outcome of FMT based on donor microbiome alone. We also demonstrate how to optimize FMT for different required outcomes. RESULTS: We show, using multiple microbiome properties, that donor and post-transplant recipient microbiota differ widely and propose a tool to predict the recipient post-transplant condition (engraftment success and clinical outcome), using only the donors' microbiome and, when available, demographics for transplantations from humans to either mice or other humans (with or without antibiotic pre-treatment). We validated the predictor using a de novo FMT experiment highlighting the possibility of choosing transplants that optimize an array of required goals. We then extend the method to characterize a best-planned transplant (bacterial cocktail) by combining the predictor and a generative genetic algorithm (GA). We further show that a limited number of taxa is enough for an FMT to produce a desired microbiome or phenotype. CONCLUSIONS: Off-the-shelf FMT requires recipient-independent optimized FMT selection. Such a transplant can be from an optimal donor or from a cultured set of microbes. We have here shown the feasibility of both types of manipulations in mouse and human recipients. Video Abstract.

The Underlying Changes in Serum Metabolic Profiles and Efficacy Prediction in Patients with Extensive Ulcerative Colitis Undergoing Fecal Microbiota Transplantation.

(1) Background: Fecal microbiota transplantation (FMT) is an effective treatment for ulcerative colitis (UC). Metabolomic techniques would assist physicians in clinical decision-making. (2) Methods: Patients with active UC undergoing FMT were enrolled in the study and monitored for 3 months. We explored short-term changes in the serum metabolic signatures of groups and the association between baseline serum metabolomic profiles and patient outcomes. (3) Results: Forty-four eligible patients were included in the analysis. Of them, 50.0% and 29.5% achieved clinical response and clinical remission, respectively, 3 months post-FMT. The top two significantly altered pathways in the response group were vitamin B6 metabolism and aminoacyl-tRNA biosynthesis. Both the remission and response groups exhibited an altered and enriched pathway for the biosynthesis of primary bile acid. We found a clear separation between the remission and non-remission groups at baseline, characterized by the higher levels of glycerophosphocholines, glycerophospholipids, and glycerophosphoethanolamines in the remission group. A random forest (RF) classifier was constructed with 20 metabolic markers selected by the Boruta method to predict clinical remission 3 months post-FMT, with an area under the curve of 0.963. (4) Conclusions: FMT effectively induced a response in patients with active UC, with metabolites partially improving post-FMT in the responsive group. A promising role of serum metabolites in the non-invasive prediction of FMT efficacy for UC demonstrated the value of metabolome-informed FMT in managing UC.

Aged gut microbiota contribute to different changes in antioxidant defense in the heart and liver after transfer to germ-free mice.

Age-associated impairment in antioxidant defense is an important cause of oxidative stress, and elderly individuals are usually associated with gut microbiota (GM) changes. Studies have suggested a potential relationship between the GM and changes in antioxidant defense in aging animals. Direct evidence regarding the impact of aging-associated shifts in GM on the antioxidant defense is lacking. The heart is a kind of postmitotic tissue, which is more prone to oxidative stress than the liver (mitotic tissue). To test and compare the influence of an aged GM on antioxidant defense changes in the heart and liver of the host, in this study, GM from young adolescent (5 weeks) or aged (20 months) mice was transferred to young adolescent (5 weeks) germ-free (GF) mice (N = 5 per group) by fecal microbiota transplantation (FMT). Four weeks after the first FMT was performed, fecal samples were collected for 16S rRNA sequencing. Blood, heart and liver samples were harvested for oxidative stress marker and antioxidant defense analysis. The results showed that mice that received young or aged microbiota showed clear differences in GM composition and diversity. Mice that received aged microbiota had a lower ratio of Bacteroidetes/Firmicutes in GM at the phylum level and an increased relative abundance of four GM genera: Akkermansia, Dubosiella, Alistipes and Rikenellaceae_RC9_gut_group. In addition, GM α-diversity scores based on the Shannon index and Simpson index were significantly higher in aged GM-treated mice. Oxidative stress marker and antioxidant defense tests showed that FMT from aged donors did not have a significant influence on malondialdehyde content in serum, heart and liver. However, the capacity of anti-hydroxyl radicals in the heart and liver, as well as the capacity of anti-superoxide anions in the liver, were significantly increased in mice with aged microbiota. FMT from aged donors increased the activities of Cu/Zn superoxide SOD (Cu/Zn-SOD), catalase (CAT) and glutathione-S-transferase in the heart, as well as the activity of Cu/Zn-SOD in the liver. Positive correlations were found between Cu/Zn-SOD activity and radical scavenging capacities. On the other hand, glutathione reductase activity and glutathione content in the liver were decreased in mice that received aged GM. These findings suggest that aged GM transplantation from hosts is sufficient to influence the antioxidant defense system of young adolescent recipients in an organ-dependent manner, which highlights the importance of the GM in the aging process of the host.

Gut microbiota: a newly identified environmental factor in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that predominantly affects women of childbearing age and is characterized by the damage to multiple target organs. The pathogenesis of SLE is complex, and its etiology mainly involves genetic and environmental factors. At present, there is still a lack of effective means to cure SLE. In recent years, growing evidence has shown that gut microbiota, as an environmental factor, triggers autoimmunity through potential mechanisms including translocation and molecular mimicry, leads to immune dysregulation, and contributes to the development of SLE. Dietary intervention, drug therapy, probiotics supplement, fecal microbiome transplantation and other ways to modulate gut microbiota appear to be a potential treatment for SLE. In this review, the dysbiosis of gut microbiota in SLE, potential mechanisms linking gut microbiota and SLE, and immune dysregulation associated with gut microbiota in SLE are summarized.

[Clinical study of 19 cases of steroid-refractory gastrointestinal acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation with fecal microbiota transplantation].

Objective: To investigate the clinical efficacy of fecal microbiota transplantation (FMT) for treating steroid-refractory gastrointestinal acute graft-versus-host disease (GI-aGVHD) . Methods: This analysis included 29 patients with hematology who developed steroid-refractory GI-aGVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Huaian Hospital Affiliated to Xuzhou Medical University from March 2017 to March 2022. Among them, 19 patients underwent FMT treatment (the FMT group) and 10 patients did not (the control group). The efficacy and safety of FMT were assessed, as well as the changes in intestinal microbiota abundance, lymphocyte subpopulation ratio, peripheral blood inflammatory cytokines, and GVHD biomarkers before and after FMT treatment. Results: ① Complete remission of clinical symptoms after FMT was achieved by 13 (68.4%) patients and 2 (20.0%) controls, with a statistically significant difference (P<0.05). Intestinal microbiota diversity increased and gradually recovered to normal levels after FMT and FMT-related infections did not occur. ②The proportion of CD3(+) and CD8(+) cells in the FMT group after treatment decreased compared with the control group, and the ratio of CD4(+), regulatory T cells (Treg), and CD4(+)/CD8(+) cells increased (all P< 0.05). The interleukin (IL) -6 concentration in the FMT group was lower than that in the control group [4.15 (1.91-5.71) ng/L vs 6.82 (2.40-8.91) ng/L, P=0.040], and the IL-10 concentration in the FMT group was higher than that in the control group [12.11 (5.69-20.36) ng/L vs 7.51 (4.10-9.58) ng/L, P=0.024]. Islet-derived protein 3α (REG3α) was significantly increased in patients with GI-aGVHD, and the REG3α level in the FMT group was lower than that in the control group after treatment [30.70 (10.50-105.00) µg/L vs 74.35 (33.50-139.50) µg/L, P=0.021]. Conclusion: FMT is a safe and effective method for the treatment of steroid-refractory GI-aGVHD by restoring intestinal microbiota diversity, regulating inflammatory cytokines, and upregulating Treg cells.

Melatonin promotes gut anti-oxidative status in perinatal rat by remodeling the gut microbiome.

Gut health is important for nutrition absorption, reproduction, and lactation in perinatal and early weaned mammals. Although melatonin functions in maintaining circadian rhythms and preventing obesity, neurodegenerative diseases, and viral infections, its impact on the gut microbiome and its function in mediating gut health through gut microbiota remain largely unexplored. In the present study, the microbiome of rats was monitoring after fecal microbiota transplantation (FMT) and foster care (FC). The results showed that FMT and FC increased intestinal villus height/crypt depth in perinatal rats. Mechanistically, the melatonin-mediated remodeling of gut microbiota inhibited oxidative stress, which led to attenuation of autophagy and inflammation. In addition, FMT and FC encouraged the growth of more beneficial intestinal bacteria, such as Allobaculum, Bifidobacterium, and Faecalibaculum, which produce more short-chain fatty acids to strengthen intestinal anti-oxidation. These findings suggest that melatonin-treated gut microbiota increase the production of SCFAs, which improve gut health by reducing oxidative stress, autophagy and inflammation. The transfer of melatonin-treated gut microbiota may be a new and effective method by which to ameliorate gut health in perinatal and weaned mammals.

Age-associated changes in the gut microbiome impact efficacy of tumor immunomodulatory treatments.

In-situ vaccination (ISV) utilizing nanoparticles (NPs) and therapeutic devices like focused ultrasound (FUS) can trigger immune-mediated killing of both treated and untreated cancer cells. However, the impact of confounding factors such as aging and gut microbiota composition on therapeutic outcomes remains poorly understood. In this study, we sequentially treated young mice (∼8 weeks) and old mice (>18 months) with bilateral melanoma using FUS and calreticulin nanoparticles (CRT-NP) to enhance immunogenic cell death. The combination of CRT-NP and FUS (CFUS) demonstrated greater efficacy in inducing regression of treated and untreated tumors in young mice compared to old mice. The diminished effectiveness in older mice was associated with significant differences in gut microbiome composition, characterized by alterations in bacterial species and splenic immune cells. Specifically, young mice exposed to CFUS exhibited higher abundance of Bacteroidetes and Verrucomicrobia, which was not observed in the aged cohorts. Turicibacter, Anaerotruncus, and Ruminiclostridium demonstrated negative correlations with CD8+ T cells but positive correlations with CD4+ T cells and MDSC cells in both age groups. Taxon set enrichment analysis revealed 58 significantly enriched host gene targets in the young cluster compared to only 11 in the aged cluster. These findings highlight the relationship between ISV treatment efficacy and gut microbiome composition, suggesting that interventions such as diet modification, probiotics, or fecal microbiota transplantation may hold potential as therapeutic strategies to enhance immune responses against solid tumors.

Washed microbiota transplantation targeting both gastrointestinal and extraintestinal symptoms in patients with irritable bowel syndrome.

OBJECTIVE: Fecal microbiota transplantation (FMT) has been reported with the treatment potential for irritable bowel syndrome (IBS). However, the knowledge of its effect on extraintestinal symptoms of IBS is limited. This study aimed to evaluate the efficacy of the improved methodology of FMT, washed microbiota transplantation (WMT), on sleep disturbances, and psychological and gastrointestinal symptoms among patients with IBS. METHODS: This was a prospective observational study involving patients with IBS who underwent WMT. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. The Gastrointestinal Symptom Rating Scale (GSRS) and IBS Severity Scoring System (IBS-SSS) were used to evaluate gastrointestinal symptoms and IBS severity, respectively. The Self-rating Depression Scale (SDS) and Self-rating Anxiety Scale (SAS) were used to evaluate depression and anxiety, respectively. All the symptoms were evaluated at baseline and one month after WMT. A multiple logistic regression model was used to determine the predictive factors of sleep improvement one month after WMT. RESULTS: Seventy-three patients with IBS were included in the study. Sleep quality (Z = -4.211, P < 0.001), anxiety (Z = -4.775, P < 0.001), depression (Z = -4.610, P < 0.001), gastrointestinal symptoms (Z = -5.364, P < 0.001), and IBS severity (Z = -6.468, P < 0.001) significantly improved one month after WMT in all patients. The scores of the five components of PSQI including subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, and sleep disturbances decreased in 52 patients with poor sleep quality (all P < 0.05). Baseline sleep duration scores were identified as an independent predictive factor of sleep improvement one month after WMT in patients with poor sleep quality (OR 2.180 [95% CI = 1.017-4.673]; P = 0.045). Patients that experienced sleep improvement demonstrated greater alleviation in depression (Z = -1.990, P = 0.047) and IBS severity (Z = -2.486, P = 0.013) compared with patients without sleep improvement. CONCLUSION: This study suggested that WMT might be a promising therapy for patients with IBS, especially those with comorbid sleep and psychological disorders.