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1.
Methods Mol Biol ; 2761: 373-396, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38427251

RESUMO

The fecal microbial transplantation (FMT) is a therapeutic transplant of fecal microbiota from healthy donors to patients. This practice is aimed at restoring eubiosis and rebalancing the enteric and systemic immune responses, and then eliminating pathogenic triggers of multiple disease, including neurodegenerative diseases. Alterations of gut microbiota (GM) affect the central nervous system (CNS) health, impacting neuro-immune interactions, synaptic plasticity, myelination, and skeletal muscle function. T-regulatory lymphocytes (Treg) are among the most important players in the pathogenesis of amyotrophic lateral sclerosis (ALS), altering the disease course. Along with circulating neuropeptides, other immune cells, and the gut-brain axis, the GM influences immunological tolerance and controls Treg's number and suppressive functions. A double-blind, controlled, multicenter study on FMT in ALS patients has been designed to evaluate if FMT can modulate neuroinflammation, by restoring Treg number, thus modifying disease activity and progression.


Assuntos
Esclerose Amiotrófica Lateral , Microbioma Gastrointestinal , Microbiota , Humanos , Transplante de Microbiota Fecal , Esclerose Amiotrófica Lateral/terapia , Microbioma Gastrointestinal/fisiologia , Protocolos Clínicos , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
Gut Microbes ; 16(1): 2327442, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38478462

RESUMO

In small series, third-party fecal microbiota transplantation (FMT) has been successful in decolonizing the gut from clinically relevant antibiotic resistance genes (ARGs). Less is known about the short- and long-term effects of FMT on larger panels of ARGs. We analyzed 226 pre- and post-treatment stool samples from a randomized placebo-controlled trial of FMT in 100 patients undergoing allogeneic hematopoietic cell transplantation or receiving anti-leukemia induction chemotherapy for 47 ARGs. These patients have heavy antibiotic exposure and a high incidence of colonization with multidrug-resistant organisms. Samples from each patient spanned a period of up to 9 months, allowing us to describe both short- and long-term effects of FMT on ARGs, while the randomized design allowed us to distinguish between spontaneous changes vs. FMT effect. We find an overall bimodal pattern. In the first phase (days to weeks after FMT), low-level transfer of ARGs largely associated with commensal healthy donor microbiota occurs. This phase is followed by long-term resistance to new ARGs as stable communities with colonization resistance are formed after FMT. The clinical implications of these findings are likely context-dependent and require further research. In the setting of cancer and intensive therapy, long-term ARG decolonization could translate into fewer downstream infections.


Assuntos
Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Humanos , Transplante de Microbiota Fecal/métodos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Microbioma Gastrointestinal/genética , Resultado do Tratamento , Resistência Microbiana a Medicamentos , Fezes
4.
Int J Mol Sci ; 25(5)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38473999

RESUMO

Emerging evidence suggests a link between atopic dermatitis (AD) and gastrointestinal disorders, particularly in relation to gut microbial dysbiosis. This study explored the potential exacerbation of AD by gut inflammation and microbial imbalances using an irritable bowel syndrome (IBS) mouse model. Chronic gut inflammation was induced in the model by intrarectal injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS), followed by a 4-week development period. We noted significant upregulation of proinflammatory cytokines in the colon and evident gut microbial dysbiosis in the IBS mice. Additionally, these mice exhibited impaired gut barrier function, increased permeability, and elevated systemic inflammation markers such as IL-6 and LPS. A subsequent MC903 challenge on the right cheek lasting for 7 days revealed more severe AD symptoms in IBS mice compared to controls. Further, fecal microbial transplantation (FMT) from IBS mice resulted in aggravated AD symptoms, a result similarly observed with FMT from an IBS patient. Notably, an increased abundance of Alistipes in the feces of IBS mice correlated with heightened systemic and localized inflammation in both the gut and skin. These findings collectively indicate that chronic gut inflammation and microbial dysbiosis in IBS are critical factors exacerbating AD, highlighting the integral relationship between gut and skin health.


Assuntos
Dermatite Atópica , Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Humanos , Animais , Camundongos , Disbiose , Microbioma Gastrointestinal/fisiologia , Fezes , Transplante de Microbiota Fecal , Inflamação
5.
World J Gastroenterol ; 30(8): 833-842, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38516241

RESUMO

The population of non-alcoholic fatty liver disease (NAFLD) patients along with relevant advanced liver disease is projected to continue growing, because currently no medications are approved for treatment. Fecal microbiota transplantation (FMT) is believed a novel and promising therapeutic approach based on the concept of the gut-liver axis in liver disease. There has been an increase in the number of pre-clinical and clinical studies evaluating FMT in NAFLD treatment, however, existing findings diverge on its effects. Herein, we briefly summarized the mechanism of FMT for NAFLD treatment, reviewed randomized controlled trials for evaluating its efficacy in NAFLD, and proposed the prospect of future trials on FMT.


Assuntos
Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/terapia , Transplante de Microbiota Fecal/efeitos adversos
6.
Front Immunol ; 15: 1324018, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38449863

RESUMO

The bidirectional communication between the gut and brain or gut-brain axis is regulated by several gut microbes and microbial derived metabolites, such as short-chain fatty acids, trimethylamine N-oxide, and lipopolysaccharides. The Gut microbiota (GM) produce neuroactives, specifically neurotransmitters that modulates local and central neuronal brain functions. An imbalance between intestinal commensals and pathobionts leads to a disruption in the gut microbiota or dysbiosis, which affects intestinal barrier integrity and gut-immune and neuroimmune systems. Currently, fecal microbiota transplantation (FMT) is recommended for the treatment of recurrent Clostridioides difficile infection. FMT elicits its action by ameliorating inflammatory responses through the restoration of microbial composition and functionality. Thus, FMT may be a potential therapeutic option in suppressing neuroinflammation in post-stroke conditions and other neurological disorders involving the neuroimmune axis. Specifically, FMT protects against ischemic injury by decreasing IL-17, IFN-γ, Bax, and increasing Bcl-2 expression. Interestingly, FMT improves cognitive function by lowering amyloid-ß accumulation and upregulating synaptic marker (PSD-95, synapsin-1) expression in Alzheimer's disease. In Parkinson's disease, FMT was shown to inhibit the expression of TLR4 and NF-κB. In this review article, we have summarized the potential sources and methods of administration of FMT and its impact on neuroimmune and cognitive functions. We also provide a comprehensive update on the beneficial effects of FMT in various neurological disorders by undertaking a detailed interrogation of the preclinical and clinical published literature.


Assuntos
AVC Isquêmico , Doenças do Sistema Nervoso , Doença de Parkinson , Acidente Vascular Cerebral , Humanos , Transplante de Microbiota Fecal , Doenças do Sistema Nervoso/terapia , Acidente Vascular Cerebral/terapia
7.
Genome Med ; 16(1): 37, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38419010

RESUMO

BACKGROUND: Multidrug-resistant (MDR) bacteria are a growing global threat, especially in healthcare facilities. Faecal microbiota transplantation (FMT) is an effective prevention strategy for recurrences of Clostridioides difficile infections and can also be useful for other microbiota-related diseases. METHODS: We study the effect of FMT in patients with multiple recurrent C. difficile infections on colonisation with MDR bacteria and antibiotic resistance genes (ARG) on the short (3 weeks) and long term (1-3 years), combining culture methods and faecal metagenomics. RESULTS: Based on MDR culture (n = 87 patients), we notice a decrease of 11.5% in the colonisation rate of MDR bacteria after FMT (20/87 before FMT = 23%, 10/87 3 weeks after FMT). Metagenomic sequencing of patient stool samples (n = 63) shows a reduction in relative abundances of ARGs in faeces, while the number of different resistance genes in patients remained higher compared to stools of their corresponding healthy donors (n = 11). Furthermore, plasmid predictions in metagenomic data indicate that patients harboured increased levels of resistance plasmids, which appear unaffected by FMT. In the long term (n = 22 patients), the recipients' resistomes are still donor-like, suggesting the effect of FMT may last for years. CONCLUSIONS: Taken together, we hypothesise that FMT restores the gut microbiota to a composition that is closer to the composition of healthy donors, and potential pathogens are either lost or decreased to very low abundances. This process, however, does not end in the days following FMT. It may take months for the gut microbiome to re-establish a balanced state. Even though a reservoir of resistance genes remains, a notable part of which on plasmids, FMT decreases the total load of resistance genes.


Assuntos
Clostridioides difficile , Infecções por Clostridium , Microbiota , Humanos , Transplante de Microbiota Fecal/métodos , Clostridioides difficile/genética , Fezes/microbiologia , Infecções por Clostridium/terapia , Infecções por Clostridium/microbiologia , Resultado do Tratamento
9.
J Virol ; 98(2): e0203523, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38299844

RESUMO

Bovine viral diarrhea virus (BVDV) is prevalent worldwide and causes significant economic losses. Gut microbiota is a large microbial community and has a variety of biological functions. However, whether there is a correlation between gut microbiota and BVDV infection and what kind of relation between them have not been reported. Here, we found that gut microbiota composition changed in normal mice after infecting with BVDV, but mainly the low abundance microbe was affected. Interestingly, BVDV infection significantly reduced the diversity of gut microbiota and changed its composition in gut microbiota-dysbiosis mice. Furthermore, compared with normal mice of BVDV infection, there were more viral loads in the duodenum, jejunum, spleen, and liver of the gut microbiota-dysbiosis mice. However, feces microbiota transplantation (FMT) reversed these effects. The data above indicated that the dysbiosis of gut microbiota was a key factor in the high infection rate of BVDV. It is found that the IFN-I signal was involved by investigating the underlying mechanisms. The inhibition of the proliferation and increase in the apoptosis of peripheral blood lymphocytes (PBL) were also observed. However, FMT treatment reversed these changes by regulating PI3K/Akt, ERK, and Caspase-9/Caspase-3 pathways. Furthermore, the involvement of butyrate in the pathogenesis of BVDV was also further confirmed. Our results showed for the first time that gut microbiota acts as a key endogenous defense mechanism against BVDV infection; moreover, targeting regulation of gut microbiota structure and abundance may serve as a new strategy to prevent and control the disease.IMPORTANCEWhether the high infection rate of BVDV is related to gut microbiota has not been reported. In addition, most studies on BVDV focus on in vitro experiments, which limits the study of its prevention and control strategy and its pathogenic mechanism. In this study, we successfully confirmed the causal relationship between gut microbiota and BVDV infection as well as the potential molecular mechanism based on a mouse model of BVDV infection and a mouse model of gut microbiota dysbiosis. Meanwhile, a mouse model which is more susceptible to BVDV provided in this study lays an important foundation for further research on prevention and control strategy of BVDV and its pathogenesis. In addition, the antiviral effect of butyrate, the metabolites of butyrate-producing bacteria, has been further revealed. Overall, our findings provide a promising prevention and control strategy to treat this infectious disease which is distributed worldwide.


Assuntos
Doença das Mucosas por Vírus da Diarreia Viral Bovina , Vírus da Diarreia Viral Bovina , Microbioma Gastrointestinal , Animais , Bovinos , Camundongos , Doença das Mucosas por Vírus da Diarreia Viral Bovina/complicações , Doença das Mucosas por Vírus da Diarreia Viral Bovina/microbiologia , Doença das Mucosas por Vírus da Diarreia Viral Bovina/terapia , Doença das Mucosas por Vírus da Diarreia Viral Bovina/virologia , Butiratos/metabolismo , Caspase 3/metabolismo , Caspase 9/metabolismo , Diarreia , Vírus da Diarreia Viral Bovina/patogenicidade , Vírus da Diarreia Viral Bovina/fisiologia , Disbiose/complicações , Disbiose/microbiologia , Disbiose/virologia , MAP Quinases Reguladas por Sinal Extracelular/imunologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Transplante de Microbiota Fecal , Interferon Tipo I/imunologia , Interferon Tipo I/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Modelos Animais de Doenças
10.
Cell Rep ; 43(2): 113728, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38300802

RESUMO

Cardiometabolic diseases are leading causes of mortality in Western countries. Well-established risk factors include host genetics, lifestyle, diet, and the gut microbiome. Moreover, gut bacterial communities and their activities can be altered by bacteriophages (also known simply as phages), bacteria-infecting viruses, making these biological entities key regulators of human cardiometabolic health. The manipulation of bacterial populations by phages enables the possibility of using phages in the treatment of cardiometabolic diseases through phage therapy and fecal viral transplants. First, however, a deeper understanding of the role of the phageome in cardiometabolic diseases is required. In this review, we first introduce the phageome as a component of the gut microbiome and discuss fecal viral transplants and phage therapy in relation to cardiometabolic diseases. We then summarize the current state of phageome research in cardiometabolic diseases and propose how the phageome might indirectly influence cardiometabolic health through gut bacteria and their metabolites.


Assuntos
Bacteriófagos , Doenças Cardiovasculares , Microbioma Gastrointestinal , Humanos , Bactérias , Transplante de Microbiota Fecal , Doenças Cardiovasculares/terapia
11.
J Hazard Mater ; 467: 133714, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38340564

RESUMO

The debris of plastics with a size < 5 mm, called microplastics, possess long-lived legacies of plastic pollution and a growing threat to human beings. The adverse effects and corresponding molecular mechanisms of microplastics are still largely unknown and must be prioritized. Antibiotics commonly co-existed with microplastics; the current study investigated the syngenetic toxic effect of doxycycline (Dox) and polystyrene microplastics (PS). Specifically, we found that Dox combined with PS exposure perturbed gut microbiota homeostasis in mice, which mediated brain lesions and inflammation with a concomitant decline in learning and memory behaviors through the gut-brain axis. Of note, PS exposure resulted in intestinal damage and structural change, but Dox did not accelerate the disruption of intestinal barrier integrity in PS-treated mice. Interestingly, fecal microbiota transplantation (FMT) can reverse neurological impairment caused by combined PS and Dox exposure via compensating gut microbes; therefore, the learning and memory abilities of mice were also recovered. This work not only provides insights into the syngenetic effect of microplastics and antibiotics and highlights their distal neurotoxicity through the gut-brain axis but also offers a promising strategy against their combined toxicity.


Assuntos
Doxiciclina , Microbioma Gastrointestinal , Humanos , Animais , Camundongos , Doxiciclina/toxicidade , Microplásticos/toxicidade , Plásticos , Poliestirenos/toxicidade , Transplante de Microbiota Fecal , Antibacterianos/toxicidade
12.
Gut Microbes ; 16(1): 2319844, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38404132

RESUMO

Patients with inflammatory bowel disease (IBD), including ulcerative colitis (UC), show an increased incidence of anxiety and depression; however, the association between UC-associated psychiatric disorders and the gut microbiota is unclear. This study aimed to examine whether gut microbiota from patients with UC can alter colonic gene expression, leading to anxiety- and depression-like behavior in mice receiving fecal microbiota transplantation (FMT). RNA sequencing transcriptome analyses revealed a difference in colonic gene expression between mice receiving FMT from patients with UC (UC-FMT mice) and those receiving FMT from healthy controls (HC-FMT mice). Gene ontology analysis revealed the downregulation of neuropeptide signaling pathways, including neuropeptide Y (NPY) expression, in the colons of UC-FMT mice. The protein levels of NPY also decreased in the colon and plasma of UC-FMT mice compared to those in HC-FMT mice. The oral administration of Enterococcus mundtii (EM), a bacterium isolated from the feces of patients with UC, reduced NPY expression in the colons of mice and induced intestinal inflammation, anxiety, and depression-like behavior. Reduced NPY protein levels were also observed in the plasma and hippocampus of EM-treated mice. Intraperitoneal administration of NPY significantly alleviated anxiety- and depressive-like behaviors induced by EM in mice. Capsular polysaccharide in EM was associated with EM-induced NPY downregulation in the colon. Analysis of Gene Expression Omnibus datasets showed markedly reduced NPY expression in the inflamed colons of patients with UC compared with that in the colons of healthy controls. In summary, EM-induced reduction in the colonic expression of NPY may be associated with a decrease in hippocampal NPY and anxiety- and depression-like behavior in mice.


Assuntos
Colite Ulcerativa , Microbioma Gastrointestinal , Humanos , Colite Ulcerativa/microbiologia , Neuropeptídeo Y/genética , Depressão , Transplante de Microbiota Fecal , Fezes/microbiologia , Ansiedade
13.
World J Gastroenterol ; 30(3): 225-237, 2024 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-38314132

RESUMO

This comprehensive review elucidates the complex interplay between gut microbiota and constipation in Parkinson's disease (PD), a prevalent non-motor symptom contributing significantly to patients' morbidity. A marked alteration in the gut microbiota, predominantly an increase in the abundance of Proteobacteria and Bacteroidetes, is observed in PD-related constipation. Conventional treatments, although safe, have failed to effectively alleviate symptoms, thereby necessitating the development of novel therapeutic strategies. Microbiological interventions such as prebiotics, probiotics, and fecal microbiota transplantation (FMT) hold therapeutic potential. While prebiotics improve bowel movements, probiotics are effective in enhancing stool consistency and alleviating abdominal discomfort. FMT shows potential for significantly alleviating constipation symptoms by restoring gut microbiota balance in patients with PD. Despite promising developments, the causal relationship between changes in gut microbiota and PD-related constipation remains elusive, highlighting the need for further research in this expanding field.


Assuntos
Doença de Parkinson , Probióticos , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/terapia , Doença de Parkinson/microbiologia , Constipação Intestinal/etiologia , Constipação Intestinal/terapia , Transplante de Microbiota Fecal/efeitos adversos , Prebióticos , Probióticos/uso terapêutico
14.
BMJ Open ; 14(2): e074625, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38320845

RESUMO

INTRODUCTION: Autism (formally autism spectrum disorder) encompasses a group of complex neurodevelopmental conditions, characterised by differences in communication and social interactions. Co-occurring chronic gastrointestinal symptoms are common among autistic individuals and can adversely affect their quality of life. This study aims to evaluate the efficacy of oral encapsulated faecal microbiome transfer (FMT) in improving gastrointestinal symptoms and well-being among autistic adolescents and adults. METHODS AND ANALYSIS: This double-blind, randomised, placebo-controlled trial will recruit 100 autistic adolescents and adults aged 16-45 years, who have mild to severe gastrointestinal symptoms (Gastrointestinal Symptoms Rating Scale (GSRS) score ≥2.0). We will also recruit eight healthy donors aged 18-32 years, who will undergo extensive clinical screening. Recipients will be randomised 1:1 to receive FMT or placebo, stratified by biological sex. Capsules will be administered over two consecutive days following an overnight bowel cleanse with follow-up assessments at 6, 12 and 26 weeks post-treatment. The primary outcome is GSRS score at 6 weeks. Other assessments include anthropometry, body composition, hair cortisol concentration, gut microbiome profile, urine/plasma gut-derived metabolites, plasma markers of gut inflammation/permeability and questionnaires on general well-being, sleep quality, physical activity, food diversity and treatment tolerability. Adverse events will be recorded and reviewed by an independent data monitoring committee. ETHICS AND DISSEMINATION: Ethics approval for the study was granted by the Central Health and Disability Ethics Committee on 24 August 2021 (reference number: 21/CEN/211). Results will be published in peer-reviewed journals and presented to both scientific and consumer group audiences. TRIAL REGISTRATION NUMBER: ACTRN12622000015741.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Gastroenteropatias , Microbioma Gastrointestinal , Adulto , Humanos , Adolescente , Transtorno Autístico/terapia , Transtorno do Espectro Autista/terapia , Transplante de Microbiota Fecal/métodos , Qualidade de Vida , Gastroenteropatias/terapia , Método Duplo-Cego , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
J Appl Microbiol ; 135(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38305096

RESUMO

AIMS: Gastrointestinal disease is a leading cause of morbidity in bottlenose dolphins (Tursiops truncatus) under managed care. Fecal microbiota transplantation (FMT) holds promise as a therapeutic tool to restore gut microbiota without antibiotic use. This prospective clinical study aimed to develop a screening protocol for FMT donors to ensure safety, determine an effective FMT administration protocol for managed dolphins, and evaluate the efficacy of FMTs in four recipient dolphins. METHODS AND RESULTS: Comprehensive health monitoring was performed on donor and recipient dolphins. Fecal samples were collected before, during, and after FMT therapy. Screening of donor and recipient fecal samples was accomplished by in-house and reference lab diagnostic tests. Shotgun metagenomics was used for sequencing. Following FMT treatment, all four recipient communities experienced engraftment of novel microbial species from donor communities. Engraftment coincided with resolution of clinical signs and a sustained increase in alpha diversity. CONCLUSION: The donor screening protocol proved to be safe in this study and no adverse effects were observed in four recipient dolphins. Treatment coincided with improvement in clinical signs.


Assuntos
Golfinho Nariz-de-Garrafa , Microbioma Gastrointestinal , Animais , Transplante de Microbiota Fecal/métodos , Estudos Prospectivos , Fezes , Resultado do Tratamento
16.
Cell Host Microbe ; 32(3): 349-365.e4, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38367621

RESUMO

Studies on fecal microbiota transplantation (FMT) have reported inconsistent connections between clinical outcomes and donor strain engraftment. Analyses of subspecies-level crosstalk and its influences on lineage transfer in metagenomic FMT datasets have proved challenging, as single-nucleotide polymorphisms (SNPs) are generally not linked and are often absent. Here, we utilized species genome bin (SGB), which employs co-abundance binning, to investigate subspecies-level microbiome dynamics in patients with autism spectrum disorder (ASD) who had gastrointestinal comorbidities and underwent encapsulated FMT (Chinese Clinical Trial: 2100043906). We found that interactions between donor and recipient microbes, which were overwhelmingly phylogenetically divergent, were important for subspecies transfer and positive clinical outcomes. Additionally, a donor-recipient SGB match was indicative of a high likelihood of strain transfer. Importantly, these ecodynamics were shared across FMT datasets encompassing multiple diseases. Collectively, these findings provide detailed insight into specific microbial interactions and dynamics that determine FMT success.


Assuntos
Transtorno do Espectro Autista , Infecções por Clostridium , Microbioma Gastrointestinal , Humanos , Transplante de Microbiota Fecal , Microbioma Gastrointestinal/genética , Trato Gastrointestinal , Fezes , Resultado do Tratamento
17.
Gastroenterology ; 166(3): 409-434, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38395525

RESUMO

BACKGROUND & AIMS: Fecal microbiota-based therapies include conventional fecal microbiota transplant and US Food and Drug Administration-approved therapies, fecal microbiota live-jslm and fecal microbiota spores live-brpk. The American Gastroenterological Association (AGA) developed this guideline to provide recommendations on the use of fecal microbiota-based therapies in adults with recurrent Clostridioides difficile infection; severe to fulminant C difficile infection; inflammatory bowel diseases, including pouchitis; and irritable bowel syndrome. METHODS: The guideline was developed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) framework to prioritize clinical questions, identify patient-centered outcomes, and conduct an evidence synthesis. The guideline panel used the Evidence-to-Decision framework to develop recommendations for the use of fecal microbiota-based therapies in the specified gastrointestinal conditions and provided implementation considerations for clinical practice. RESULTS: The guideline panel made 7 recommendations. In immunocompetent adults with recurrent C difficile infection, the AGA suggests select use of fecal microbiota-based therapies on completion of standard of care antibiotics to prevent recurrence. In mildly or moderately immunocompromised adults with recurrent C difficile infection, the AGA suggests select use of conventional fecal microbiota transplant. In severely immunocompromised adults, the AGA suggests against the use of any fecal microbiota-based therapies to prevent recurrent C difficile. In adults hospitalized with severe or fulminant C difficile not responding to standard of care antibiotics, the AGA suggests select use of conventional fecal microbiota transplant. The AGA suggests against the use of conventional fecal microbiota transplant as treatment for inflammatory bowel diseases or irritable bowel syndrome, except in the context of clinical trials. CONCLUSIONS: Fecal microbiota-based therapies are effective therapy to prevent recurrent C difficile in select patients. Conventional fecal microbiota transplant is an adjuvant treatment for select adults hospitalized with severe or fulminant C difficile infection not responding to standard of care antibiotics. Fecal microbiota transplant cannot yet be recommended in other gastrointestinal conditions.


Assuntos
Clostridioides difficile , Infecções por Clostridium , Gastroenteropatias , Doenças Inflamatórias Intestinais , Síndrome do Intestino Irritável , Microbiota , Adulto , Humanos , Síndrome do Intestino Irritável/tratamento farmacológico , Resultado do Tratamento , Gastroenteropatias/terapia , Gastroenteropatias/tratamento farmacológico , Transplante de Microbiota Fecal/efeitos adversos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infecções por Clostridium/terapia , Infecções por Clostridium/tratamento farmacológico , Antibacterianos/uso terapêutico , Recidiva
18.
Int J Mol Sci ; 25(3)2024 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-38339169

RESUMO

Ulcerative colitis is a chronic immune-mediated disease of unclear etiology, affecting people of different ages and significantly reducing the quality of life. Modern methods of therapy are mainly represented by anti-inflammatory drugs and are not aimed at a specific pathogenetic factor. In this study, we investigated the effect of transplantation of sterile stool filtrate from healthy donors on the induction of anti-inflammatory immune mechanisms. It was shown that performing such a procedure in patients with ulcerative colitis caused the appearance of T helper cells in the blood, which reacted to the content of sterile stool filtrates in an antigen-specific manner and produced IL-10. At the same time, cells of the same patients before therapy in response to the addition of sterile stool filtrates were less reactive and predominantly produced IL-4, indicating its pro-inflammatory skewing. The obtained data demonstrated the effect of an anti-inflammatory shift in the T-helper response after transplantation of sterile stool filtrate, which increased and persisted for at least three months after the procedure.


Assuntos
Colite Ulcerativa , Microbioma Gastrointestinal , Humanos , Transplante de Microbiota Fecal/métodos , Colite Ulcerativa/terapia , Colite Ulcerativa/etiologia , Qualidade de Vida , Fezes , Anti-Inflamatórios , Linfócitos T Auxiliares-Indutores
19.
Microbiol Res ; 282: 127654, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38417203

RESUMO

Abdominal obesity (AO), characterized by the excessive abdominal fat accumulation, has emerged as a significant public health concern due to its metabolic complications and escalating prevalence worldwide, posing a more pronounced threat to human health than general obesity. While certain studies have indicated that intestinal flora contributed to diet-induced general obesity, the precise involvement of gut microbiota in the development of AO, specifically the accumulation of abdominal fat, remains inadequately explored. In this study, the 16 S rDNA sequencing was employed to analyze gut flora alterations, and the intestinal microbiota dysbiosis characterized by a vanishing decline of Akkermansia was found in the AO group. Along with notable gut microbiota changes, the intestinal mucosal barrier damage and metabolic inflammation were detected, which collectively promoted metabolic dysregulation in AO. Furthermore, the metabolic inflammation and AO were ameliorated after the intestinal microbiota depletion with antibiotics (ABX) drinking, underscoring a significant involvement of gut microbiota dysbiosis in the progression of AO. More importantly, our findings demonstrated that the transplantation of healthy intestinal flora successfully reversed the gut microbiota dysbiosis, particularly the decline of Akkermansia in the AO group. The gut flora reshaping has led to the repair of gut barrier damage and mitigation of metabolic inflammation, which ultimately ameliorated abdominal fat deposition. Our study established the role of interactions between gut flora, mucus barrier, and metabolic inflammation in the development of AO, thereby offering a theoretical foundation for the clinical application of fecal microbiota transplantation (FMT) as a treatment for AO.


Assuntos
Transplante de Microbiota Fecal , Microbiota , Camundongos , Humanos , Animais , Obesidade Abdominal , Disbiose/terapia , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Inflamação , Camundongos Endogâmicos C57BL
20.
Ecotoxicol Environ Saf ; 273: 116140, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38417315

RESUMO

Triphenyltin (TPT) is a widely used biocide known for its high toxicity to various organisms, including humans, and its potential contribution to environmental pollution. The aging process leads to progressive deterioration of physiological functions in the elderly, making them more susceptible to the toxic effects of environmental pollutants. This study aimed to investigate the mitigating effect of fecal transplantation in young mice on the toxicological impairment caused by TPT exposure. For the study, 18-month-old mice were divided into four groups with six replicates each. The control group was fed a basal diet, the TPT group was exposed to 3.75 mg/Kg TPT, the feces group received fecal transplantation from 8-week-old young mice, and the combined group was exposed to 3.75 mg/Kg TPT after receiving fecal transplantation. Compared with the elderly control group, TPT induced significant upregulation of mRNA expression of pro-inflammatory factors (IL-1ß, IL-6, TNF-α), while the anti-inflammatory factor gene IL-10 was significantly suppressed. The mRNA expression of intestinal barrier proteins (Claudin, Occludin, Muc2) was also significantly downregulated. However, fecal transplantation in young mice alleviated TPT-induced changes in inflammatory factors, ameliorated oxidative stress, and increased the activities of antioxidant enzymes (including SOD, CAT, GSH-Px). Further analysis using 16 s RNA showed that exposure to TPT led to changes in the composition of the intestinal flora. Untargeted metabolomics observations of feces from older mice revealed that exposure to TPT resulted in altered fecal metabolites. Fecal transplantation in young mice altered the microbiota of TPT-exposed older mice, especially by enhancing the levels of core probiotics. Similar beneficial effects were observed through untargeted metabolomics. Overall, this study highlights the potential benefits of young fecal transplantation in protecting the elderly from the toxicity of TPT, offering a promising approach to improve healthy aging.


Assuntos
Transplante de Microbiota Fecal , Compostos Orgânicos de Estanho , Humanos , Camundongos , Animais , Idoso , Lactente , Compostos Orgânicos de Estanho/toxicidade , Fezes , RNA Mensageiro/metabolismo
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