Role of intestinal microbiota in transplantation outcomes.
Ontology highlight
ABSTRACT:
SUBMITTER: Taur Y
PROVIDER: S-EPMC4656136 | biostudies-literature | 2015 Jun-Sep
REPOSITORIES: biostudies-literature
Publications
Role of intestinal microbiota in transplantation outcomes.
Taur Ying Y Jenq Robert R RR Ubeda Carles C van den Brink Marcel M Pamer Eric G EG
Best practice & research. Clinical haematology 20150601 2-3
While allogeneic hematopoietic stem cell transplantations have a curative potential, infections and graft-versus-host disease remain significant problems. The intestinal microbiota can influence responses to cancer chemotherapy and the role of the microbiota in affecting allogeneic hematopoietic stem cell transplantation outcomes is increasingly appreciated. The following paper discusses the most recent developments in this area. ...[more]
Similar Datasets
Project description:Inflammatory bowel disease (IBD) is a complex set of diseases that lead to chronic inflammation in the gastrointestinal tract. Although the etiology of IBD is not fully understood, it is well-known that the intestinal microbiota is associated with the development and maintenance of IBD. Manipulation of the gut microbiota, therefore, may represent a target for IBD therapy. Fecal microbiota transplantation (FMT), where fecal microbiota from a healthy donor is transplanted into a patient's GI tract, is already a successful therapy for Clostridium difficile infection. FMT is currently being explored as a potential therapy for IBD as well. In this review, the associations between the gut microbiota and IBD and the emerging data on FMT for IBD will be discussed.
| S-EPMC5479396 | biostudies-literature
Project description:Background and aimsUlcerative colitis (UC) is a chronic inflammatory disease that affects many people. One of the possible ways to treat UC is fecal microbiota transplantation (FMT). In this study, changes in the intestinal microbiome and clinical outcomes of 20 patients with UC after FMT were estimated.MethodsFMT enemas were administrated ten times, once a day, and fecal microbiota from three donors was used for each enema. The clinical outcomes were assessed after eight weeks and then via a patient survey. The 16S rRNA profiles of the gut microbiota were compared between three samplings: samples from 20 patients with UC before and after FMT and samples from 18 healthy volunteers.ResultsClinical remission was achieved in 19 (95%) patients at week 8. Adverse events occurred in five patients, including one non-responder. A significant increase in average biodiversity was shown in samples after FMT compared to samples before FMT, as well as a decrease in the proportion of some potentially pathogenic bacteria.ConclusionThe efficacy of FMT for UC treatment was confirmed; however, the duration of remission varied substantially, possibly due to different characteristics of the initial microbiota of patients. Targeted analysis of a patient's microbiome before FMT could increase the treatment efficacy.
| S-EPMC10743744 | biostudies-literature
Project description:Intestinal microbial dysbiosis is associated with various intestinal and extraintestinal disorders. Fecal microbiota transplantation (FMT), a type of fecal bacteriotherapy, is considered an effective therapeutic option for recurrent Clostridium difficile infection (rCDI) and also has important value in other intestinal diseases including irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). The purpose of this review is to discuss promising therapeutic value in extraintestinal diseases associated with gut microbial dysbiosis, including liver, metabolic, chronic kidney, neuropsychiatric, allergic, autoimmune, and hematological diseases as well as tumors.
| S-EPMC6699279 | biostudies-other
Project description:BackgroundIncreasing evidence suggests that the intestinal microbiota plays an important role in liver diseases. However, the dynamics of the intestinal microbiota during liver transplantation (LT) and its potential role in clinical course remain unknown.MethodsWe prospectively analyzed the intestinal microbiota of 38 patients who underwent LT in Kyoto University Hospital. We characterized the microbial compositions of fecal specimens from LT patients using a metagenomics approach by an Illumina MiSeq platform. We analyzed the diversity of microbiota sequentially from pretransplantation until 2 months after LT and also compared the microbiota during an episode of acute cellular rejection (ACR) and bloodstream infections (BSI) to the microbial composition of time-matched fecal specimens obtained from patients who did not experience ACR or BSI, respectively.ResultsThree hundred twenty fecal specimens were analyzed. Dynamic changes were observed in the microbial composition of LT recipients during the perioperative period. Over the course of LT, the mean diversity index decreased during the first 3 weeks after LT and gradually increased during our observation period. The loss of intestinal microbiota diversity was associated with high Child-Pugh scores, high model for end-stage liver disease scores, ACR, and BSI. At the family level, Bacteroides, Enterobacteriaceae, Streptococcaceae, and Bifidobacteriaceae were increased whereas Enterococcaceae, Lactobacillaceae, Clostridiaceae, Ruminococcaceae, and Peptostreptococcaceae were decreased in ACR patients.ConclusionsThe microbiota of LT patients was associated with the severity of liver diseases and the presence of ACR and BSI. These results lay the groundwork for more comprehensive investigations of microbiota characteristics to identify diagnostic markers for transplant health and to guide intervention strategies to improve transplant outcomes.
| S-EPMC5381737 | biostudies-literature
Project description:Under normal conditions our intestines are inhabited by trillions of diverse microorganisms composing the intestinal microbiota, which are mostly non-pathogenic anaerobic commensal bacteria vital for the maintenance of immune homeostasis. The composition and diversity of the intestinal microbiota can be disturbed by various factors including diet, antibiotics, and exposure to intestinal pathogens. Alterations of the intestinal microbiota contributes to many diseases including graft-vs.-host disease (GVHD), a life threatening complication that occurs after allogeneic hematopoietic cell transplantation (allo-HCT) caused by an allogeneic reaction of donor T cells against recipient target tissues. Intestinal GVHD is most difficult to treat and connected to a high mortality. Due to recent advances in high-throughput sequencing technology, composition of the microbiome during allo-HCT has been characterized, and some common patterns have been identified. Metabolites produced by intestinal bacteria were shown to promote intestinal tissue homeostasis and immune tolerance post-allo-HCT. In this review, we discuss the role of the intestinal microbiota and metabolites in the context of acute GVHD. Moreover, novel therapeutic approaches that aim at protecting or regenerating intestinal cell populations will be highlighted.
| S-EPMC6344415 | biostudies-literature
Project description:Despite a growing understanding of the link between intestinal inflammation and resident gut microbes, longitudinal studies of human flora before initial onset of intestinal inflammation have not been reported. Here, we demonstrate in murine and human recipients of allogeneic bone marrow transplantation (BMT) that intestinal inflammation secondary to graft-versus-host disease (GVHD) is associated with major shifts in the composition of the intestinal microbiota. The microbiota, in turn, can modulate the severity of intestinal inflammation. In mouse models of GVHD, we observed loss of overall diversity and expansion of Lactobacillales and loss of Clostridiales. Eliminating Lactobacillales from the flora of mice before BMT aggravated GVHD, whereas reintroducing the predominant species of Lactobacillus mediated significant protection against GVHD. We then characterized gut flora of patients during onset of intestinal inflammation caused by GVHD and found patterns mirroring those in mice. We also identified increased microbial chaos early after allogeneic BMT as a potential risk factor for subsequent GVHD. Together, these data demonstrate regulation of flora by intestinal inflammation and suggest that flora manipulation may reduce intestinal inflammation and improve outcomes for allogeneic BMT recipients.
| S-EPMC3348096 | biostudies-literature
Project description:Previous studies suggest a link between intestinal microbiota and porcine feed efficiency (FE). Therefore, we investigated whether fecal microbiota transplantation (FMT) in sows and/or neonatal offspring, using inocula derived from highly feed-efficient pigs, could improve offspring FE. Pregnant sows were assigned to control or FMT treatments and the subsequent offspring to control treatment, FMT once (at birth), or FMT four times (between birth and weaning). FMT altered sow fecal and colostrum microbiota compositions and resulted in lighter offspring body weight at 70 and 155 days of age when administered to sows and/or offspring. This was accompanied by FMT-associated changes within the offspring's intestinal microbiota, mostly in the ileum. These included transiently higher fecal bacterial diversity and load and numerous compositional differences at the phylum and genus levels (e.g., Spirochaetes and Bacteroidetes at high relative abundances and mostly members of Clostridia, respectively), as well as differences in the abundances of predicted bacterial pathways. In addition, intestinal morphology was negatively impacted, duodenal gene expression altered, and serum protein and cholesterol concentrations reduced due to FMT in sows and/or offspring. Taken together, the results suggest poorer absorptive capacity and intestinal health, most likely explaining the reduced body weight. An additive effect of FMT in sows and offspring also occurred for some parameters. Although these findings have negative implications for the practical use of the FMT regime used here for improving FE in pigs, they nonetheless demonstrate the enormous impact of early-life intestinal microbiota on the host phenotype. IMPORTANCE Here, for the first time, we investigate FMT as a novel strategy to modulate the porcine intestinal microbiota in an attempt to improve FE in pigs. However, reprogramming the maternal and/or offspring microbiome by using fecal transplants derived from highly feed-efficient pigs did not recapitulate the highly efficient phenotype in the offspring and, in fact, had detrimental effects on lifetime growth. Although these findings may not be wholly attributable to microbiota transplantation, as antibiotic and purgative were also part of the regime in sows, similar effects were also seen in offspring, in which these interventions were not used. Nonetheless, additional work is needed to unravel the effects of each component of the FMT regime and to provide additional mechanistic insights. This may lead to the development of an FMT procedure with practical applications for the improvement of FE in pigs, which could in turn improve the profitability of pig production.
| S-EPMC5864416 | biostudies-literature
Project description:Different gastrointestinal disorders, including inflammatory bowel diseases (IBD), have been linked to alterations of the gut microbiota composition, namely dysbiosis. Fecal microbiota transplantation (FMT) is considered an encouraging therapeutic approach for ulcerative colitis patients, mostly as a consequence of normobiosis restoration. We recently showed that therapeutic effects of FMT during acute experimental colitis are linked to functional modulation of the mucosal immune system and of the gut microbiota composition. Here we analysed the effects of therapeutic FMT administration during chronic experimental colitis, a condition more similar to that of IBD patients, on immune-mediated mucosal inflammatory pathways. Mucus and feces from normobiotic donors were orally administered to mice with established chronic Dextran Sodium Sulphate (DSS)-induced colitis. Immunophenotypes and functions of infiltrating colonic immune cells were evaluated by cytofluorimetric analysis. Compositional differences in the intestinal microbiome were analyzed by 16S rRNA sequencing. Therapeutic FMT in mice undergoing chronic intestinal inflammation was capable to decrease colonic inflammation by modulating the expression of pro-inflammatory genes, antimicrobial peptides, and mucins. Innate and adaptive mucosal immune cells manifested a reduced pro-inflammatory profile in FMT-treated mice. Finally, restoration of a normobiotic core ecology contributed to the resolution of inflammation. Thus, FMT is capable of controlling chronic intestinal experimental colitis by inducing a concerted activation of anti-inflammatory immune pathways, mechanistically supporting the positive results of FMT treatment reported in ulcerative colitis patients.
| S-EPMC6628315 | biostudies-literature
Project description:Nonalcoholic steatohepatitis (NASH) is a serious disease threatening public health, and its pathogenesis remains largely unclear. Recent scientific research has shown that intestinal microbiota and its metabolites have an important impact on the development of NASH. A balanced intestinal microbiota contributes to the maintenance of liver homeostasis, but when the intestinal microbiota is disequilibrated, it serves as a source of pathogens and molecules that lead to NASH. In this review, we mainly emphasize the key mechanisms by which the intestinal microbiota and its metabolites affect NASH. In addition, recent clinical trials and animal studies on the treatment of NASH by regulating the intestinal microbiota through prebiotics, probiotics, synbiotics and FMT have also been briefly elaborated. With the increasing understanding of interactions between the intestinal microbiota and liver, accurate and personalized detection and treatment methods for NASH are expected to be established.
| S-EPMC8861316 | biostudies-literature
Project description:Alteration of the gut microbiota has been associated with different gastrointestinal disorders. Normobiosis restoration by faecal microbiota transplantation (FMT) is considered a promising therapeutic approach, even if the mechanisms underlying its efficacy are at present largely unknown. Here we sought to elucidate the functional effects of therapeutic FMT administration during experimental colitis on innate and adaptive immune responses in the intestinal mucosa. We show that therapeutic FMT reduces colonic inflammation and initiates the restoration of intestinal homeostasis through the simultaneous activation of different immune-mediated pathways, ultimately leading to IL-10 production by innate and adaptive immune cells, including CD4+ T cells, iNKT cells and Antigen Presenting Cells (APC), and reduces the ability of dendritic cells, monocytes and macrophages to present MHCII-dependent bacterial antigens to colonic T cells. These results demonstrate the capability of FMT to therapeutically control intestinal experimental colitis and poses FMT as a valuable therapeutic option in immune-related pathologies.
| S-EPMC6281577 | biostudies-literature