High stearic acid diet modulates gut microbiota and aggravates acute graft-versus-host disease.
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ABSTRACT:
SUBMITTER: Yang B
PROVIDER: S-EPMC8298483 | biostudies-literature | 2021 Jul
REPOSITORIES: biostudies-literature
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High stearic acid diet modulates gut microbiota and aggravates acute graft-versus-host disease.
Yang Bingyu B Zhang Xianfeng X Gong Huanle H Huang Yuhui Y Wang Chang C Liu Haiyan H Dong Chen C Ma Shoubao S Wu Xiaojin X Wu Depei D
Signal transduction and targeted therapy 20210723 1
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Project description:AimThe gut microbiota has been reported to be associated with acute graft-versus-host disease (aGvHD) in hematopoietic stem cell transplantation (HSCT). Dynamic surveillance of the microbiota is required to understand the detailed pathogenesis involved in the process of aGvHD.MethodsFecal samples were collected prospectively at four timepoints, including pre-HSCT (T1), graft infusion (T2), neutrophil engraftment (T3), and 30 days after transplantation (T4). Fecal samples were profiled by 16S ribosomal RNA gene sequencing to assess the microbiota composition.ResultsFrom the T1 to T4 timepoint, the diversity of the gut microbiota decreased, and the dominant species also changed, with a decrease in the obligate anaerobic bacteria and a shift toward a "pathogenic community". Compared with non-aGvHD patients, aGvHD patients had a lower abundance of Roseburia at T1 and a higher abundance of Acinetobacter johnsonii at T2. Furthermore, Acinetobacter johnsonii was negatively correlated with the secretion of IL-4 and TNF-α. At T3, Rothia mucilaginos was demonstrated to be linked with a decreased risk of aGvHD, which was accompanied by decreased secretion of IL-8. At T4, higher abundances of Lactobacillus paracasei and Acinetobacter johnsonii were identified to be related with aGvHD. Lactobacillus paracasei was associated with the downregulation of IL-10, and Acinetobacter johnsonii was associated with the downregulation of IL-2 and TNF-α.ConclusionsDynamic changes in gut microbiota composition and related cytokines were found to be related to aGvHD, including pathogenic or protective changes. These findings suggested that manipulation of gut microbiota at different timepoints might be a promising avenue for preventing or treating this common complication.
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Project description:We previously reported a protective association between single nucleotide polymorphisms (SNPs; rs4415345G and rs4610776A alleles) of Paneth cell α-defensin-5 against acute graft-versus-host disease (aGVHD). Because dysbiosis has been associated with aGVHD, we hypothesized that these SNPs may have a gut microbiota signature. In Lasso regression analysis of 248 healthy individuals, rs4415345G was associated with a higher abundance of Odoribacter splanchnicus, an anaerobic butyrogenic commensal. In multivariable analysis of data from 613 allogeneic haematopoietic cell transplant recipients, peri-engraftment presence of O. splanchnicus was associated with ~50% lower risk for grade II-IV aGVHD (hazard ratio 0·53, 95% confidence interval 0·28-1·00, P = 0·05). O. splanchnicus may protect rs4415345G individuals against aGVHD.
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Project description:BackgroundThe gut microbiota and derived metabolites play a key role in regulating host physiology. Diet is identified as a key regulatory factor of the microbiota composition and, potentially, of subsequent functionalities. Demonstrating the role of diet may be complex as most human studies are cross-sectional and dietary intervention is often accompanied by hygienic changes. The objective of the present study was to investigate the impact of an industrial diet on the modulation of the microbiota and targeted functionalities using a canine "natural" model.ResultsWe carried out a controlled dietary trial in a cohort of Tunisian semi-stray dogs. We made a transition from a natural diet to an industrial kibble diet and monitored the composition of the fecal microbiota, the concentration of short-chain fatty acids (SCFA) and bile acids (BAs), and protease activities. We demonstrated that dietary change significantly decreased fecal primary bile acids levels and protease activities. Interestingly, correlation analyses demonstrated that variation of specific microbial genera were associated with modulated physiological parameters.ConclusionsOur study reveals that an industrial diet induces beneficial changes in microbial composition and functions characterised by increased diversity, synthesis of SCFA and secondary bile acids production, stressing the key role of the diet-microbiota-dog crosstalk.
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Project description:Haematopoietic stem cell transplantation (HSCT) is central to the management of many haematological disorders. A frequent complication of HSCT is acute graft-versus-host disease (GVHD), a condition in which immune cells from the donor attack healthy recipient tissues. The gastrointestinal system is among the most common sites affected by acute GVHD, and severe manifestations of acute GVHD of the gut portends a poor prognosis in patients after HSCT. Acute GVHD of the gastrointestinal tract presents both diagnostic and therapeutic challenges. Although the clinical manifestations are nonspecific and overlap with those of infection and drug toxicity, diagnosis is ultimately based on clinical criteria. As reliable serum biomarkers have not yet been validated outside of clinical trials, endoscopic and histopathological evaluation continue to be utilized in diagnosis. Once a diagnosis of gastrointestinal acute GVHD is established, therapy with systemic corticosteroids is typically initiated, and non-responders can be treated with a wide range of second-line therapies. In addition to treating the underlying disease, the management of complications including profuse diarrhoea, severe malnutrition and gastrointestinal bleeding is paramount. In this Review, we discuss strategies for the diagnosis and management of acute GVHD of the gastrointestinal tract as they pertain to the practising gastroenterologist.
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