Butyrate-producing bacteria supplemented in vitro to Crohn’s disease patient microbiota increased butyrate production and enhanced intestinal epithelial barrier integrity (original) (raw)
Related papers
International Journal of Pharmaceutics
Poorly formulated probiotic supplements intended for oral administration often fail to protect bacteria from the challenges of human digestion, meaning bacteria do not reach the small intestine in a viable state. As a result, the ability of probiotics to influence the human gut microbiota has not been proven. Here we show how (i) considered formulation of an aqueous probiotic suspension can facilitate delivery of viable probiotic bacteria to the gut and (ii) quantitate the effect of colonisation and proliferation of specific probiotic species on the human gut microbiota, using an in-vitro gut model. Our data revealed immediate colonisation and growth of three probiotic species in the luminal and mucosal compartments of the proximal and distal colon, and growth of a fourth species in the luminal proximal colon, leading to higher proximal and distal colonic lactate concentrations. The lactate stimulated growth of lactate-consuming bacteria, altering the bacterial diversity of the microbiota and resulting in increased short-chain fatty acid production, especially butyrate. Additionally, an immunomodulatory effect of the probiotics was seen; production of anti-inflammatory cytokines (IL-6 and IL-10) was increased and production of inflammatory chemokines (MCP-1, CXCL 10 and IL-8.) was reduced. The results indicate that the probiotic species alone do not result in a clinical effect; rather, they facilitate modulation of the gut microbiota composition and metabolic activity thereby influencing the immune response.
Journal of Crohn's & colitis, 2018
Alterations in short chain fatty acid metabolism, particularly butyrate, have been reported in inflammatory bowel disease, but results have been conflicting because of small study numbers and failure to distinguish disease type, activity or other variables such as diet. We performed a comparative assessment of the capacity of the microbiota for butyrate synthesis, by quantifying butyryl-CoA:acetate CoA-transferase [BCoAT] gene content in stool from patients with Crohn's disease [CD; n = 71], ulcerative colitis [UC; n = 58] and controls [n = 75], and determined whether it was related to active vs inactive inflammation, microbial diversity, and composition and/or dietary habits. BCoAT gene content was quantified by quantitative polymerase chain reaction [qPCR]. Disease activity was assessed clinically and faecal calprotectin concentration measured. Microbial composition was determined by sequencing 16S rRNA gene. Dietary data were collected using an established food frequency ques...
Neurogastroenterology & Motility, 2020
BackgroundButyrate has shown anti‐inflammatory and regenerative properties, providing symptomatic relief when orally supplemented in patients suffering from various colonic diseases. We investigated the effect of a colonic‐delivery formulation of butyrate on the fecal microbiota of patients with inflammatory bowel diseases (IBDs).MethodsIn this double‐blind, placebo‐controlled, pilot study, 49 IBD patients (n = 19 Crohn's disease, CD and n = 30 ulcerative colitis, UC) were randomized to oral administration of microencapsulated‐sodium‐butyrate (BLM) or placebo for 2 months, in addition to conventional therapy. Eighteen healthy volunteers (HVs) were recruited to provide a healthy microbiota model of the local people. Fecal microbiota from stool samples was assessed by 16S sequencing. Clinical disease activity and quality of life (QoL) were evaluated before and after treatment.Key ResultsAt baseline, HVs showed a different microbiota composition compared with IBD patients. Sodium‐b...
World Journal of Gastroenterology, 2014
Although it is now known that the human body is colonized by a wide variety of microbial populations in different parts (such as the mouth, pharynx and respiratory system, the skin, the gastro-and urogenital tracts), many effects of the complex interactions between the human host and microbial symbionts are still not completely understood. The dysbiosis of the gastrointestinal tract microbiota is considered to be one of the most important contributing factors in the development of many gastrointestinal diseases such as inflammatory bowel disease, irritable bowel syndrome and colorectal cancer, as well as systemic diseases like obesity, diabetes, atherosclerosis and non-alcoholic fatty liver disease. Fecal microbial transplantations appear to be promising therapies for dysbiosis-associated diseases; however, probiotic microorganisms have been growing in popularity due to increasing numbers of studies proving that certain strains present health promoting properties, among them the beneficial balance of the intestinal microbiota. Inflammatory bowel diseases and
Gut Microbes
Host-microbial cross-talk plays a crucial role in maintenance of gut homeostasis. However, how microbiota-derived metabolites, e.g., butyrate, regulate functions of neutrophils in the pathogenesis of inflammatory bowel disease (IBD) remains elusive. We sought to investigate the effects of butyrate on IBD neutrophils and elucidate the therapeutic potential in regulating mucosal inflammation. Peripheral neutrophils were isolated from IBD patients and healthy donors, and profiles of proinflammatory cytokines and chemokines were determined by qRT-PCR and ELISA, respectively. The migration and release of neutrophil extracellular traps (NETs) were studied by a Transwell model and immunofluorescence, respectively. The in vivo role of butyrate in regulating IBD neutrophils was evaluated in a DSS-induced colitis model in mice. We found that butyrate significantly inhibited IBD neutrophils to produce proinflammatory cytokines, chemokines, and calprotectins. Blockade of GPCR signaling with pertussis toxin (PTX) did not interfere the effects whereas pan-histone deacetylase (HDAC) inhibitor, trichostatin A (TSA) effectively mimicked the role of butyrate. Furthermore, in vitro studies confirmed that butyrate suppressed neutrophil migration and formation of NETs from both CD and UC patients. RNA sequencing analysis revealed that the immunomodulatory effects of butyrate on IBD neutrophils were involved in leukocyte activation, regulation of innate immune response and response to oxidative stress. Consistently, oral administration of butyrate markedly ameliorated mucosal inflammation in DSS-induced murine colitis through inhibition of neutrophil-associated immune responses such as proinflammatory mediators and NET formation. Our data thus reveal that butyrate constrains neutrophil functions and may serve as a novel therapeutic potential in the treatment of IBD.
Probiotics and Their Use in Inflammatory Bowel Disease
Alternative Therapies in Health & Medicine, 2018
Context • Crohn's disease and ulcerative colitis result in similar gastrointestinal (GI) symptoms, including pain, diarrhea, stools with mucus or blood, and ulceration or tissue damage within the alimentary canal. Gut microbiota play a crucial role in triggering, maintaining, and exacerbating inflammatory bowel disease (IBD). Probiotics might help to rebalance the gut flora in a positive way, shifting from pro-to anti-inflammatory. Objectives • The study intended to investigate the safety and use of probiotics and the biological effects of probiotic bacteria on IBD. Design • The research team performed a literature review. The team conducted a database search in April 2015 using Google Scholar and PubMed to find studies relevant to probiotics and their use in IBD. Only papers that were published in English were considered, and all available years in each database were searched. The initial search identified 38 published articles, for which the research team obtained full texts and independently read them in full to identify those papers suitable for inclusion in the review. Setting • The study took place in the main library of the University of Lahore (Islamabad, Pakistan). Results • Many strains of probiotics exist, but the most common strains available today are (1) the Bifidobacterium species, (2) Enterococcus faecium, (4) the Lactobacillus strains, (4) Saccharomyces boulardii, (5) the Bacillus species, and (6) Pediococcus, all used to produce beneficial health effects. These species showed their beneficial effects on the host using different mechanisms involving (1) production of proteins, quorum sensing signaling inhibitors, butyrate, immunoglobulin A, and short-chain fatty acids; (2) decreased production of tumor necrosis factor alpha and interleukin 8; (3) increased expression of mucin 2; and (4) increased upregulation of defensin. Conclusions • Studies on probiotics in animal models of IBD are promising, and clinical results in IBD patients are encouraging; however, the data are limited, and few studies are placebo controlled. Additional placebo-controlled, double-blind studies in IBD are required before recommendations can be offered for routine use of probiotics in IBD. Additional organisms may eventually be developed through genetic engineering. The current evidence also indicates that probiotic effects are strain specific; they do not act through the same mechanisms nor are all probiotics indicated for the same health conditions. More research is needed to determine what strains and at what dose probiotics become more useful as part of a clinical intervention. (Altern Ther Health Med. 2018;24(3):16-23.)
Gut, 2013
Objective Bacteria play an important role in the onset and perpetuation of intestinal inflammation in inflammatory bowel disease (IBD). Unlike in Crohn's disease (CD), in which dysbiosis has been better characterised, in ulcerative colitis (UC), only small cohorts have been studied and showed conflicting data. Therefore, we evaluated in a large cohort if the microbial signature described in CD is also present in UC, and if we could characterise predominant dysbiosis in UC. To assess the functional impact of dysbiosis, we quantified the bacterial metabolites. Design The predominant microbiota from 127 UC patients and 87 age and sex-matched controls was analysed using denaturing gradient gel electrophoresis (DGGE) analysis. Differences were quantitatively validated using real-time PCR. Metabolites were quantified using gas chromatography-mass spectrometry. Results Based on DGGE analysis, the microbial signature previously described in CD was not present in UC. Real-time PCR analysis revealed a lower abundance of Roseburia hominis (p<0.0001) and Faecalibacterium prausnitzii (p<0.0001) in UC patients compared to controls. Both species showed an inverse correlation with disease activity. Short-chain fatty acids (SCFA) were reduced in UC patients (p=0.014), but no direct correlation between SCFA and the identified bacteria was found. Conclusions The composition of the fecal microbiota of UC patients differs from that of healthy individuals: we found a reduction in R hominis and F prausnitzii, both well-known butyrate-producing bacteria of the Firmicutes phylum. These results underscore the importance of dysbiosis in IBD but suggest that different bacterial species contribute to the pathogenesis of UC and CD.