P882 Dietary interventions may modify intestinal inflammation via altering microbial composition—a cross-over trial

AbstractPatients with ulcerative colitis (UC) have an altered gut microbiota composition, but the microbial relationship to disease activity needs to be further elucidated. Therefore, temporal dynamics of the fecal microbial community during remission and flare was determined. Fecal samples were collected at 2–6 time-points from UC patients during established disease (cohort EST) and at diagnosis (cohort NEW). Sampling range for cohort EST was 3–10 months and for cohort NEW 36 months. Relapses were monitored for an additional three years for cohort EST. Microbial composition was assessed by Genetic Analysis GA-map Dysbiosis Test, targeting ≥ 300 bacteria. Eighteen patients in cohort EST (8 with maintained remission and 10 experiencing a flare), provided 71 fecal samples. In cohort NEW, 13 patients provided 49 fecal samples. The microbial composition showed no clustering related to disease activity in any cohort. Microbial dissimilarity was higher between than within patients for both cohorts, irrespective of presence of a flare. Microbial stability within patients was constant over time with no major shift in overall composition nor modification in the abundance of any specific species. Microbial composition was not affected by intensified medical treatment or linked to future disease course. Thus in UC, the gut microbiota is highly stable irrespective of disease stage, disease activity or treatment escalation. This suggests that prolonged dietary interventions or repeated fecal transplantations are needed to be able to induce permanent alterations of the gut microbiota.

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The Microbiome as a Therapy in Pouchitis and Ulcerative Colitis

Nutrients ◽

10.3390/nu13061780 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1780

Author(s):

Jean-Frédéric LeBlanc ◽

Jonathan P. Segal ◽

Lucia Maria de Campos Braz ◽

Ailsa L. Hart

Keyword(s):

Ulcerative Colitis ◽

Gut Microbiome ◽

Intestinal Inflammation ◽

Omega 3 Fatty Acids ◽

Omega 3 ◽

Faecal Microbiota ◽

Dietary Interventions ◽

Therapeutic Landscape ◽

Microbiome Diversity ◽

Inflammatory Bowel

The gut microbiome has been implicated in a range of diseases and there is a rapidly growing understanding of this ecosystem’s importance in inflammatory bowel disease. We are yet to identify a single microbe that causes either ulcerative colitis (UC) or pouchitis, however, reduced microbiome diversity is increasingly recognised in active UC. Manipulating the gut microbiome through dietary interventions, prebiotic and probiotic compounds and faecal microbiota transplantation may expand the therapeutic landscape in UC. Specific diets, such as the Mediterranean diet or diet rich in omega-3 fatty acids, may reduce intestinal inflammation or potentially reduce the risk of incident UC. This review summarises our knowledge of gut microbiome therapies in UC and pouchitis.

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Overexpression of human alpha-Synuclein leads to dysregulated microbiome/metabolites with ageing in a rat model of Parkinson disease

10.1101/2020.12.23.424226 ◽

2020 ◽

Author(s):

Yogesh Singh ◽

Christoph Trautwein ◽

Joan Romani ◽

Madhuri S Salker ◽

Peter H Neckel ◽

...

Keyword(s):

Nervous System ◽

Rat Model ◽

Intestinal Inflammation ◽

Short Chain Fatty Acids ◽

Alpha Synuclein ◽

Transgenic Rat ◽

Microbial Composition ◽

Specific Alteration ◽

Metabolites Production ◽

Transgenic Rat Model

AbstractSince Braak’s hypothesis stating that sporadic Parkinson’s disease follows a specific progression of the pathology from the peripheral to the central nervous system and can be monitored by detecting accumulation of the alpha-Synuclein protein. There is growing interest in understanding how the gut (commensal) microbiome can regulate alpha-Synuclein accumulation which can lead to PD. We studied a transgenic rat model overexpressing the human alpha-Synuclein and found that the protein overexpression resulted in gut alpha-Synuclein expression and aggregation in the gut neurons with advancing age. A progressive gut microbial composition alteration characterized by the reduction of Firmicutes to Bacteroidetes ratio could be detected in the young transgenic rat model and interestingly this ratio was then increased with aging. This observation was accompanied in older animals by intestinal inflammation, increase gut permeability and a robust alteration in metabolites production characterized by the increase of succinate level in the feces and serum. Manipulation of the gut bacteria by short-term antibiotics treatment revealed a complete loss of short-chain fatty acids (SCFAs) and reduction in succinate levels. Although antibiotics treatment did not change alpha-synuclein expression in the enteric nervous system of the colon, it can reduce alpha-synuclein expression in the olfactory bulb of the transgenic rats. In summary, synchronous with ageing, our data emphasize that the gut microbiome dysbiosis leads to a specific alteration of gut metabolites which are reflected in the serum and can be modulated by the environment.

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Fruit Consumption is Associated with Alterations in Microbial Composition and Lower Rates of Pouchitis

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz053 ◽

2019 ◽

Vol 13 (10) ◽

pp. 1265-1272 ◽

Cited By ~ 7

Author(s):

L Godny ◽

N Maharshak ◽

L Reshef ◽

I Goren ◽

L Yahav ◽

...

Keyword(s):

Microbial Diversity ◽

Intestinal Inflammation ◽

Disease Recurrence ◽

Rrna Gene ◽

Microbial Composition ◽

Fruit Consumption ◽

Entire Cohort ◽

Faecal Samples ◽

16S Rrna Gene Pyrosequencing ◽

Microbial Analysis

Abstract Background Patients with ulcerative colitis [UC] who undergo proctocolectomy with an ileal pouch–anal anastomosis commonly develop pouch inflammation [pouchitis]. Pouchitis develops in a previously normal small intestine and may involve environmental factors. We explored whether diet and microbiota alterations contributed to the pathogenesis of pouchitis. Methods Patients were recruited and prospectively followed at a comprehensive pouch clinic. Pouch behaviour was clinically defined as a normal pouch [NP] or pouchitis. Patients completed Food Frequency Questionnaires [FFQs]. Faecal samples were analysed for microbial composition [16S rRNA gene pyrosequencing]. Results Nutritional evaluation was performed in 172 patients [59% females], and of these, faecal microbial analysis was performed in 75 patients (microbiota cohort: NP [n = 22], pouchitis [n = 53]). Of the entire cohort, a subgroup of 39 [22.6%] patients had NP at recruitment [NP cohort]. Of these, 5 [12.8%] developed pouchitis within a year. Patients at the lowest tertile of fruit consumption [<1.45 servings/day] had higher rates of pouchitis compared with those with higher consumption [30.8% vs 3.8%, log rank, p = 0.03]. Fruit consumption was correlated with microbial diversity [r = 0.35, p = 0.002] and with the abundance of several microbial genera, including Faecalibacterium [r = 0.29, p = 0.01], Lachnospira [r = 0.38, p = 0.001], and a previously uncharacterized genus from the Ruminococcaceae family [r = 0.25, p = 0.05]. Reduction in fruit consumption over time was associated with disease recurrence and with reduced microbial diversity [Δ = –0.8 ± 0.3, p = 0.008]. Conclusions Fruit consumption is associated with modification of microbial composition, and lower consumption was correlated with the development of pouchitis. Thus, fruit consumption may protect against intestinal inflammation via alteration of microbial composition.

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Apple peel polyphenols: a key player in the prevention and treatment of experimental inflammatory bowel disease

Clinical Science ◽

10.1042/cs20160524 ◽

2016 ◽

Vol 130 (23) ◽

pp. 2217-2237 ◽

Cited By ~ 26

Author(s):

Marie-Claude Denis ◽

Denis Roy ◽

Pantea Rahmani Yeganeh ◽

Yves Desjardins ◽

Thibault Varin ◽

...

Keyword(s):

Fruits And Vegetables ◽

Intestinal Inflammation ◽

Therapeutic Effects ◽

Microbial Composition ◽

Beneficial Effects ◽

Apple Peel ◽

Bowel Diseases ◽

Clinical Benefits ◽

Inflammatory Bowel ◽

Underlying Mechanisms

Diets rich in fruits and vegetables may reduce oxidative stress (OxS) and inflammation via several mechanisms. These beneficial effects may be due to their high polyphenol content. The aims of the present study are to evaluate the preventive and therapeutic aspects of polyphenols in dried apple peel powder (DAPP) on intestinal inflammation while elucidating the underlying mechanisms and clinical benefits. Induction of intestinal inflammation in mice was performed by oral administration of the inflammatory agent dextran sulfate sodium (DSS) at 2.5% for 10 days. Physiological and supraphysiological doses of DAPP (200 and 400 mg/kg/day respectively) were administered by gavage for 10 days pre- and post-DSS treatment. DSS-mediated inflammation caused weight loss, shortening of the colon, dystrophic detachment of the epithelium, and infiltration of mono- and poly-morphonuclear cells in the colon. DSS induced an increase in lipid peroxidation, a down-regulation of antioxidant enzymes, an augmented expression of myeloperoxidase (MPO) and cyclooxygenase-2 (COX-2), an elevated production of prostaglandin E2 (PGE2) and a shift in mucosa-associated microbial composition. However, DAPP normalized most of these abnormalities in preventive or therapeutic situations in addition to lowering inflammatory cytokines while stimulating antioxidant transcription factors and modulating other potential healing pathways. The supraphysiological dose of DAPP in therapeutic situations also improved mitochondrial dysfunction. Relative abundance of Peptostreptococcaceae and Enterobacteriaceae bacteria was slightly decreased in DAPP-treated mice. In conclusion, DAPP exhibits powerful antioxidant and anti-inflammatory action in the intestine and is associated with the regulation of cellular signalling pathways and changes in microbiota composition. Evaluation of preventive and therapeutic effects of DAPP may be clinically feasible in individuals with intestinal inflammatory bowel diseases.

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Intestinal microbiota and inflammatory bowel diseases

Journal of Korean Medical Association ◽

10.5124/jkma.2021.64.9.588 ◽

2021 ◽

Vol 64 (9) ◽

pp. 588-595

Author(s):

Chang Soo Eun

Keyword(s):

Intestinal Microbiota ◽

Inflammatory Bowel Diseases ◽

Intestinal Inflammation ◽

Microbial Composition ◽

Mucosal Permeability ◽

Next Generation Sequencing Technology ◽

Early Results ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

And Function

Background: The prevalence of inflammatory bowel diseases (IBD) has been rapidly increasing over the past several decades in Korea. IBD appears to be resulted from inappropriate and chronic activation of the mucosal immune system driven by stimuli such as intestinal microbiota and various environmental factors in genetically susceptible individuals.Current Concepts: Recent advances in next-generation sequencing technology have identified alterations in the composition and function of the intestinal microbiota in individuals with IBD. Dysbiosis in patients with IBD is characterized by decreased bacterial diversity combined with an expansion of putative aggressive species and a reduction in protective species. Altered microbial composition and function in IBD correlates with increased immune stimulation, epithelial dysfunction, or enhanced mucosal permeability. Thus, dysbiosis may play an essential role in the pathogenesis of IBD.Discussion and Conclusion: Although it is currently unclear whether dysbiosis is a cause or consequence of intestinal inflammation in IBD, several microbial-based and microbial-targeted therapies have yielded promising early results.

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79 Fruit Consumption May Protect Against the Development of Intestinal Inflammation via Modification of Microbial Composition

Gastroenterology ◽

10.1016/s0016-5085(16)30196-2 ◽

2016 ◽

Vol 150 (4) ◽

pp. S21

Author(s):

Lihi Godny ◽

Nitsan Maharshak ◽

Lior Yahav ◽

Naomi Fliss Isakov ◽

Uri Gophna ◽

...

Keyword(s):

Intestinal Inflammation ◽

Microbial Composition ◽

Fruit Consumption

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The Impact of CKD on Uremic Toxins and Gut Microbiota

Toxins ◽

10.3390/toxins13040252 ◽

2021 ◽

Vol 13 (4) ◽

pp. 252

Author(s):

Jacek Rysz ◽

Beata Franczyk ◽

Janusz Ławiński ◽

Robert Olszewski ◽

Aleksanda Ciałkowska-Rysz ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Microbial Community ◽

Kidney Disease ◽

Gut Microbiota ◽

Intestinal Inflammation ◽

Adverse Outcomes ◽

Uremic Toxins ◽

Dietary Interventions ◽

Stress Injury ◽

The Impact

Numerous studies have indicated that the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD) is strictly associated with the accumulation of toxic metabolites in blood and other metabolic compartments. This accumulation was suggested to be related to enhanced generation of toxins from the dysbiotic microbiome accompanied by their reduced elimination by impaired kidneys. Intestinal microbiota play a key role in the accumulation of uremic toxins due to the fact that numerous uremic solutes are generated in the process of protein fermentation by colonic microbiota. Some disease states, including CKD, are associated with the presence of dysbiosis, which can be defined as an “imbalanced intestinal microbial community with quantitative and qualitative changes in the composition and metabolic activities of the gut microbiota”. The results of studies have confirmed the altered composition and functions of gut microbial community in chronic kidney disease. In the course of CKD protein-bound uremic toxins, including indoxyl sulfate, p-cresyl glucuronide, p-cresyl sulfate and indole-3-acetic acid are progressively accumulated. The presence of chronic kidney disease may be accompanied by the development of intestinal inflammation and epithelial barrier impairment leading to hastened systemic translocation of bacterial-derived uremic toxins and consequent oxidative stress injury to the kidney, cardiovascular and endocrine systems. These findings offer new therapeutic possibilities for the management of uremia, inflammation and kidney disease progression and the prevention of adverse outcomes in CKD patients. It seems that dietary interventions comprising prebiotics, probiotics, and synbiotics could pose a promising strategy in the management of uremic toxins in CKD.

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2 EFFECTS OF AN IBD-ASSOCIATED MICROBIAL COMMUNITY STATE ON INTESTINAL INFLAMMATION IN HUMANIZED GNOTOBIOTIC MICE

Inflammatory Bowel Diseases ◽

10.1093/ibd/zaa010.103 ◽

2020 ◽

Vol 26 (Supplement_1) ◽

pp. S40-S40

Author(s):

Venu Lagishetty ◽

Nerea Arias ◽

Tien Dong ◽

Meg Hauer ◽

William Katzka ◽

...

Keyword(s):

Microbial Community ◽

Intestinal Inflammation ◽

Fecal Microbiota ◽

Wild Type ◽

Microbial Composition ◽

Germ Free ◽

First Degree Relatives ◽

Gnotobiotic Mice

Abstract Background and Aims We previously reported that 20% of unaffected first-degree relatives of pediatric IBD patients share the same microbial community structure (OTU-type) as IBD patients. This suggests that a preexisting dysbiosis can predispose to the development of IBD. The aims of this study were to establish that microbial community types identified in the family cohort could be reconstituted in gnotobiotic mice for further translational studies and to assess for any direct effects of this microbiota on intestinal inflammation. Methods Over 100 germ-free wild-type C57/BL6 mice were colonized for 4 weeks in the UCLA gnotobiotic facility with fecal microbiota from 30 human donors belonging to each of four groups from the pediatric family cohort: unaffected first-degree relatives with OTU-type 1, unaffected first-degree relatives with the IBD-associated OTU-type 2, Crohn’s disease (CD) with OTU-type 1, CD with OTU-type 2. Each group was represented by 8 human donors (n=3–4 mice/donor) with the exception of CD OTU-type 1 (only 5 donors available in the cohort). In addition, 35 eight week old germ-free IL-10-/- C57/BL6 mice were colonized for 12 weeks with fecal microbiota from 4 CD OTU-type 2 donors and 4 unaffected OTU-type 1 donors (n=4–5/donor). Luminal and mucosal microbial composition in the colon and small intestine was evaluated by 16S rRNA sequencing. Intestinal inflammation was assessed in the small intestine and colon by semiquantitative scoring of H&E stained sections. Results Donor-specific microbial composition was observed in the humanized gnotobiotic mice with clear separation between recipients of donor OTU-type 1 vs. OTU-type 2 stool. Parallel differences in differentially abundant microbes and microbial diversity were seen in these gnotobiotic mice as in the original human donors. No histologic evidence was found for colitis, enteritis, or fibrosis in wild-type colonized mice. However, fecal lipocalin was increased two-fold increase in recipients of OTU-type 2 microbiota from CD patients relative to the other three groups. CD humanized IL-10-/- mice exhibited lower microbial diversity and distinct microbial composition compared to non-IBD humanized IL-10-/- mice, mirroring differences in the human donors. Mice colonized with CD microbiota had increased histological disease severity in the colon and cecum (p=0.05) compared to mice colonized with non-IBD microbiota. Conclusion Our results demonstrate that human microbial community states identified in the pediatric IBD cohort could be reconstituted in gnotobiotic mice for translational studies. Moreover, CD-associated dysbiosis exacerbated colitis severity. These data support the concept that dysbiosis plays a direct role in promoting intestinal inflammation and provide an experimental framework for further mechanistic studies of IBD-associated microbial communities.

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