Stool Short-chain Fatty Acids Research Articles

The impact of 5-hydroxytryptophan supplementation on sleep quality and gut microbiota composition in older adults: A randomized controlled trial

Background and AimsSleep quality is a pivotal part of health and there is growing evidence on the association between gut microbiota composition and sleep quality. 5-Hydroxytryptophan (5-HTP) is known as a precursor of the sleep regulating neurotransmitter and hormone however, efficacy of 5-HTP supplementation for improving sleep quality in older adults is unclear. Hence, the aim of this study is to assess the impact of 5-HTP supplementation on sleep quality and gut microbiota composition in older adults. MethodsThis is a single-blinded, 12-week parallel randomized controlled. Thirty older adults (66 ± 3 years) in Singapore were randomly assigned to either consume or not consume 100 mg 5-HTP daily. Every 4 weeks, sleep quality was assessed via both subjective (Pittsburg Sleep Quality Index) and objective (actigraphy watch) measures. A global sleep score (GSS) was obtained from the PSQI, where a GSS>5 defines as poor sleeper while a GSS≤5 defines as good sleeper. Blood serotonin level, urine melatonin concentration, gut microbiota composition and stool short chain fatty acids (SCFA) content was assessed at week 0 and 12. This study was registered in clinicaltrials.gov as NCT04078724 (https://clinicaltrials.gov/ct2/show/NCT04078724) Results5-HTP supplementation showed an overall favorable effect on certain sleep quality components and an increase in serum serotonin concentration. In particular, at week 12, not good sleepers but poor sleepers with 5-HTP supplementation were able to significantly improve subjective GSS (ΔSL5-HTP: -2.80 ± 1.10 mins, p-value=0.005). In addition, they showed an increase in microbiota diversity (Simpson5-HTP vs. SimpsonControl: 0.037 ± 0.032 a.u. vs. -0.007 ± 0.022 a.u.; pinteraction: 0.013) and relative abundance of SCFA producing bacteria in the gut. Conclusions5-HTP supplementation can improve certain sleep quality components in older adults and this benefit was more prominently observed in poor sleepers. 5-HTP was also able to improve the gut microbiota composition in poor sleepers.

Effects of a low FODMAP diet on the symptom management of patients with irritable bowel syndrome: a systematic umbrella review with the meta-analysis of clinical trials.

A low FODMAP diet (LFD) is a common restrictive diet to manage the symptoms of irritable bowel syndrome (IBS). However, there is no consensus on the alleviating effects of this diet. Herein, a systematic umbrella review with meta-analysis was conducted to investigate the effect of an LFD on IBS symptoms and its secondary outcomes in patients, which were not reported in previous meta-analyses. We performed a systematic literature search in PubMed, Scopus, and ISI Web of Science up to December 2023. The methodological quality of systematic reviews and their included trials was evaluated using AMSTAR 2 and the Cochrane risk of bias, respectively. The certainty of the evidence tool was evaluated using the GRADE approach. The data related to IBS symptoms, quality of life (QoL), microbiome diversity, and stool short-chain fatty acids were extracted. A random-effect (if RCTs ≥ 6) or fixed-effect model (if RCTs < 5) was used to recalculate effect sizes and 95% CIs and report them in both qualitative and quantitative terms (pooled risk ratio, Hedges' g, and weighted mean difference). A total of 658 articles were initially identified, with 11 meta-analyses and 24 RCTs reporting 28 outcomes with 1646 participants included. An LFD significantly affected the clinical improvement of total symptoms according to the IBS-SSS questionnaire (RR: 1.42; 95% CI: 1.02, 1.97; P = 0.04) in all the subtypes of IBS and also had favorable effects on stool consistency (WMD: -0.48; 95% CI: -0.902, -0.07) and frequency (WMD: -0.36; 95% CI: -0.61, -0.10) and some other GI symptoms in both less and more than 4 weeks of diet intervention except for stool consistency, which needed more than 4 weeks of LFD implementation. A significant QoL improvement was observed but not in the anxiety and depression state. Furthermore, some studies showed that an LFD may increase fecal pH and dysbiosis and reduce SCFA and the abundance of Bifidobacterium. In conclusion, an LFD can alleviate symptoms and QoL in IBS patients, although dysbiosis may occur. Considering the low certainty of evidence, strong RCTs with more appropriate designs are needed.

Genetic and gut microbiome determinants of SCFA circulating and fecal levels, postprandial responses and links to chronic and acute inflammation

ABSTRACT Short-chain fatty acids (SCFA) are involved in immune system and inflammatory responses. We comprehensively assessed the host genetic and gut microbial contribution to a panel of eight serum and stool SCFAs in two cohorts (TwinsUK, n = 2507; ZOE PREDICT-1, n = 328), examined their postprandial changes and explored their links with chronic and acute inflammatory responses in healthy individuals and trauma patients. We report low concordance between circulating and fecal SCFAs, significant postprandial changes in most circulating SCFAs, and a heritable genetic component (average h2 : serum = 14%(SD = 14%); stool = 12%(SD = 6%)). Furthermore, we find that gut microbiome can accurately predict their fecal levels (AUC>0.71) while presenting weaker associations with serum. Finally, we report different correlation patterns with inflammatory markers depending on the type of inflammatory response (chronic or acute trauma). Our results illustrate the breadth of the physiological relevance of SCFAs on human inflammatory and metabolic responses highlighting the need for a deeper understanding of this important class of molecules.

1131-P: Gut Microbial Differences in Youth with Obesity and Type 1 Diabetes (T1D)

Gut microbial differences are associated with and thought to contribute separately to obesity and to type 1 diabetes development. Obesity is increasingly prevalent in type 1 diabetes, creating management problems and higher rate of diabetes complications. To test how obesity may influence the gut microbiome, we analyzed stool samples for gut microbial and metabolite differences in lean (n=27, BMI: 5-85%) and obese (n=21, BMI: ≥95%) youth with type 1 diabetes. Participants were aged 15.3±2.2 y (42% female, 94% White), with A1c 7.8±1.3% and diabetes duration 5.1±4.4 y. Bacterial community analysis using metagenomic shotgun sequencing showed that within each BMI group, there were no differences in within sample species (α) diversity. There were significant dissimilarities in species (β) diversity between BMI groups (Fig 1A). Linear Discriminant Analysis Effect Size (LEfSe) showed a differential distribution of significantly abundant taxa in either the lean or obese groups (Fig. 1B). Functional profiling showed specific pathways are differentially enriched in the groups (Fig. 1C-D). Interestingly, stool short chain fatty acids (beneficial microbial metabolites) were higher in the obese compared to the lean group (p&amp;lt;0.05). This is a paradoxical finding that warrants further investigation. In summary, our findings show links between the microbiome and metabolite composition, and obesity in type 1 diabetes and could lead to therapeutic targets in the gut. Disclosure H.M. Ismail: Consultant; Rise Therapeutics. D. Perera: None. R.K. Mandal: None. S. Javornik Cregeen: None. L. DiMeglio: Consultant; Abata Therapeutics, Vertex Pharmaceuticals Incorporated. Advisory Panel; Merck &amp; Co., Inc. T.S. Hannon: Advisory Panel; Eli Lilly and Company. C. Evans-Molina: Advisory Panel; Provention Bio, Inc., DiogenX, Avotres Inc., Neurodon, MaiCell Therapeutics. Other Relationship; Isla Technology, Bristol-Myers Squibb Company, Nimbus Therapeutics. Research Support; Lilly, Astellas Pharma Inc. N. Schmidt: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (1K23DK129799-01A1)

Plasma, urine, and stool metabolites in response to dietary rice bran and navy bean supplementation in adults at high-risk for colorectal cancer.

Dietary intake of whole grains and legumes and adequate physical activity (PA) have been associated with reduced colorectal cancer (CRC) risk. A single-blinded, two-arm, randomized, placebo-controlled pilot trial was implemented to evaluate the impact of a 12-week dietary intervention of rice bran + navy bean supplementation and PA education on metabolite profiles and the gut microbiome among individuals at high risk of CRC. Adults (n=20) were randomized 1:1 to dietary intervention or control. All participants received PA education at baseline. Sixteen study foods were prepared with either heat-stabilized rice bran + navy bean powder or Fibersol®-2 as a placebo. Intervention participants consumed 30 g rice bran + 30 g navy bean powder daily; those in the control group consumed 10 g placebo daily. Non-targeted metabolite profiling was performed by UPLC-MS/MS to evaluate plasma, urine, and stool at 0, 6, and 12 weeks. Stool was also analyzed for primary and secondary bile acids (BAs) and short chain fatty acids (SCFAs) by UPLC-MS/MS and microbial community structure via 16S amplicon sequencing. Two-way ANOVA was used to compare differences between groups for metabolites, and mixed models were used to compare differences between groups for BAs, SCFAs, and alpha and beta diversity measures of microbial community structure. Across biological matrices, the intervention resulted in changes to several amino acid and lipid metabolites, compared to control. There was a 2.33-fold difference in plasma (p<0.001) and a 3.33-fold difference in urine (p=0.008) for the amino acid S-methylcysteine at 12 weeks. Fold-differences to 4-methoxyphenol sulfate in plasma and urine after 6 and 12 weeks (p<0.001) was a novel result from this combined rice bran and navy bean intervention in people. A 2.98-fold difference in plasma (p=0.002) and a 17.74-fold difference in stool (p=0.026) was observed for the lipid octadecenedioylcarnitine at 12 weeks. For stool BAs, 3-oxocholic acid was increased at 12 weeks compared to control within a subset of individuals (mean difference 16.2 ug/uL, p=0.022). No significant differences were observed between groups for stool SCFAs or microbial community structure. Dietary intake of rice bran + navy beans demonstrates beneficial modulation of host and gut microbial metabolism and represents a practical and affordable means of increasing adherence to national guidelines for CRC control and prevention in a high-risk population.

Analysis of correlations between gut microbiota, stool short chain fatty acids, calprotectin and cardiometabolic risk factors in postmenopausal women with obesity: a cross-sectional study

BackgroundMicrobiota and its metabolites are known to regulate host metabolism. In cross-sectional study conducted in postmenopausal women we aimed to assess whether the microbiota, its metabolites and gut barrier integrity marker are correlated with cardiometabolic risk factors and if microbiota is different between obese and non-obese subjects.MethodsWe analysed the faecal microbiota of 56 obese, postmenopausal women by means of 16S rRNA analysis. Stool short chain fatty acids, calprotectin and anthropometric, physiological and biochemical parameters were correlates to microbiome analyses.ResultsAlpha-diversity was inversely correlated with lipopolysaccharide (Rho = − 0.43, FDR P (Q) = 0.004). Bray–Curtis distance based RDA revealed that visceral fat and waist circumference had a significant impact on metabolic potential (P = 0.003). Plasma glucose was positively correlated with the Coriobacteriaceae (Rho = 0.48, Q = 0.004) and its higher taxonomic ranks, up to phylum (Actinobacteria, Rho = 0.46, Q = 0.004). At the metabolic level, the strongest correlation was observed for the visceral fat (Q < 0.15), especially with the DENOVOPURINE2-PWY, PWY-841 and PWY0-162 pathways. Bacterial abundance was correlated with SCFAs, thus some microbiota-glucose relationships may be mediated by propionate, as indicated by the significant average causal mediation effect (ACME): Lachnospiraceae (ACME 1.25, 95%CI (0.10, 2.97), Firmicutes (ACME 1.28, 95%CI (0.23, 3.83)) and Tenericutes (ACME − 0.39, 95%CI (− 0.87, − 0.03)). There were significant differences in the distribution of phyla between this study and Qiita database (P < 0.0001).ConclusionsMicrobiota composition and metabolic potential are associated with some CMRF and fecal SCFAs concentration in obese postmenopausal women. There is no unequivocal relationship between fecal SCFAs and the marker of intestinal barrier integrity and CMRF. Further studies with appropriately matched control groups are warranted to look for causality between SCFAs and CMRF.

LBSUN309 The Effect Of Prebiotics In Newly Diagnosed Youth With Type 1 Diabetes (T1D)

Abstract Acetylated and butyrylated high amylose starch (HAMS-AB) is a prebiotic that is effective in T1D prevention in mouse models. It alters the gut microbiome profile towards bacterial fermenters with increases short chain fatty acids (SCFA) production which improves glycemia, insulin sensitivity and secretion. The objective of this pilot study is to assess the effect of oral HAMS-AB for 4 weeks on glycemia, microbial metabolite and SCFA production in newly diagnosed (&amp;lt;2 years of diagnosis) youth with T1D. Thus far, we have enrolled 7 subjects with 1 early drop out due to nausea secondary to the prebiotic. The mean±SD age in the remaining 6 was 14.4±1.8 yrs, diabetes duration 18.6±6.3 months, 4/6 were female and White, all with BMI of &amp;lt;85th%. The prebiotic was safe and well-tolerated in all 6 who remained in the study. We assessed glycemia changes pre and post-intervention and the percent time in range (TIR) from continuous glucose monitoring data over a 4 week period increased significantly: 61. 0% vs. 71.8%, X2 18.2, p=0. 001. Stool SCFA levels were measured in 4 subjects, and butyrate levels increased post-prebiotic (8.1±9.8 vs 22.6± 6.4mmol SCFA/kg fecal material, p=0. 047). Serum and plasma Hippurate levels (a microbial metabolite associated with increased gut bacterial diversity and improved glycemia) increased significantly after 4 weeks of prebiotic consumption compared to before in all 6 individuals (p=0. 028 for serum and p=0. 033 for plasma, respectively). In summary, the prebiotic HAMS-AB was safe in adolescents with T1D. It significantly increased the percent TIR, serum and plasma Hippurate levels and stool butyrate levels. Enrollment continues as collection of samples from more participants should allow for a more conclusive analysis. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Evaluation of Stool Short Chain Fatty Acids Profiles in the First Year of Life With Childhood Atopy-Related Outcomes.

IntroductionShort chain fatty acids (SCFAs) are the main intestinal intermediate and end products of metabolism of dietary fibers/polyphenols by the gut microbiota. The aim of this study was to evaluate the biological implication of stool SCFA profiles determined in the first year of life on the clinical presentation of allergic outcomes in childhood.MethodsFrom the Growing Up in Singapore Toward healthy Outcomes (GUSTO) cohort, a sub-cohort of 75 participants was recruited. Scheduled questionnaire data was collected for cumulative prevalence of physician-diagnosed eczema, wheezing with the use of nebuliser, and allergen sensitization till the age of 8 years. Stool samples collected at week 3 and months 3, 6 and 12 were quantitated for 9 SCFAs using LC/MS/MS. SCFA data were grouped into lower (below the 25th) and higher (above the 75th percentiles) categories. Generalized Linear Mixed Models was employed to analyse longitudinal association between SCFAs and atopy-related outcomes.ResultsChildren with lower stool butyric acid levels (≤25th percentile) over the first 3 time points had higher odds ratio (OR) for wheezing (adjOR = 14.6), eczema (adjOR = 13.2), food sensitization (adjOR = 12.3) and combined outcomes of both wheezing and eczema (adjOR = 22.6) till age 8 years, compared to those with higher levels (≥75 percentile). Additionally, lower longitudinal levels of propionic acid (≤25th percentile) over 4 time points in first year of life was associated with recurrent wheezing (≥2 episodes) till 8 years (adjOR = 7.4) (adj p < 0.05).ConclusionOur results suggest that relatively low levels of gut SCFAs in early life are associated with increased susceptibility to atopic-related outcomes in childhood.

A Fructo-Oligosaccharide Prebiotic Is Well Tolerated in Adults Undergoing Allogeneic Hematopoietic Stem Cell Transplantation: A Phase I Dose-Escalation Trial

Alterations of the gut microbiota after allogeneic hematopoietic cell transplantation (allo-HCT) are a key factor in the development of transplant-related complications such as graft-versus-host disease (GVHD). Interventions that preserve the gut microbiome hold promise to improve HCT-associated morbidity and mortality. Murine models demonstrate that prebiotics such as fructo-oligosaccharides (FOSs) may increase gut levels of short-chain fatty acids (SCFAs) such as butyrate and consequently induce proliferation of immunomodulatory FOXP3+CD4+ regulatory T cells (Tregs), which impact GVHD risk. We conducted a pilot phase I trial to investigate the maximum tolerated dose of FOS in patients undergoing reduced-intensity allo-HCT (n = 15) compared with concurrent controls (n = 16). We administered the FOS starting at pretransplant conditioning and continuing for a total of 21 days. We characterized the gut microbiome using shotgun metagenomic sequencing, measured stool short-chain fatty acids (SCFAs) using liquid chromatography–mass spectrometry, and determined peripheral T cell concentrations using cytometry by time-of-flight. We found that FOS was safe and well-tolerated at 10 g/d without significant adverse effects in patients undergoing allo-HCT. Community-level gut microbiota composition differed significantly on the day of transplant (day 0) between patients receiving FOS and concurrent controls; however, FOS-associated alterations of the gut microbiota were not sustained after transplant. Although the impact of FOS was fleeting, transplantation itself impacted a substantial number of taxa over time. In our small pilot trial, no significant differences were observed in gut microbial metabolic pathways, stool SCFAs, or peripheral Tregs, although Tregs trended higher in those patients who received FOS. A marker of CD4+ T cell activation (namely, CTLA4+) was significantly higher in patients receiving FOS, whereas a non-significant trend existed for FOP3+CD4+ Treg cells, which were higher in those receiving FOS compared with controls. FOS is well tolerated at 10 g/d in patients undergoing reduced-intensity allo-HCT. Although the alterations in gut microbiota and peripheral immune cell composition in those receiving FOS are intriguing, additional studies are required to investigate the use of prebiotics in HCT recipients.

Alterations in fecal short chain fatty acids (SCFAs) and branched short-chain fatty acids (BCFAs) in men with benign prostatic hyperplasia (BPH) and metabolic syndrome (MetS).

Gut microbiome-derived short-chain fatty acids (SCFAs) emerge in the process of fermentation of polysaccharides that resist digestion (dietary fiber, resistant starch). SCFAs have a very high immunomodulatory potential and ensure local homeostasis of the intestinal epithelium, which helps maintain the intestinal barrier. We analyzed the association between stool SCFAs levels acetic acid (C 2:0), propionic acid (C 3:0), isobutyric acid (C 4:0i), butyric acid (C 4:0n), isovaleric acid (C 5:0i) valeric acid (C 5:0n), isocaproic acid (C 6:0i), and caproic acid (C 6:0n)) in aging man with benign prostatic hyperplasia (BPH) and healthy controls. The study involved 183 men (with BPH, n = 103; healthy controls, n = 80). We assessed the content of SCFAs in the stool samples of the study participants using gas chromatography. The levels of branched SCFAs (branched-chain fatty acids, BCFAs): isobutyric acid (C4:0i) (p = 0.008) and isovaleric acid (C5:0i) (p < 0.001) were significantly higher in patients with BPH than in the control group. In healthy participants isocaproic acid (C6:0i) predominated (p = 0.038). We also analyzed the relationship between stool SCFA levels and serum diagnostic parameters for MetS. We noticed a relationship between C3:0 and serum lipid parameters (mainly triglycerides) in both healthy individuals and patients with BPH with regard to MetS. Moreover we noticed relationship between C4:0i, C5:0i and C6:0i and MetS in both groups. Our research results suggest that metabolites of the intestinal microflora (SCFAs) may indicate the proper function of the intestines in aging men, and increased BCFAs levels are associated with the presence of BPH.

Impact of 2'-Fucosyllactose on Gut Microbiota Composition in Adults with Chronic Gastrointestinal Conditions: Batch Culture Fermentation Model and Pilot Clinical Trial Findings.

Intestinal dysbiosis has been described in patients with certain gastrointestinal conditions including irritable bowel syndrome (IBS) and ulcerative colitis. 2′-fucosyllactose (2′-FL), a prebiotic human milk oligosaccharide, is considered bifidogenic and butyrogenic. To assess prebiotic effects of 2′-FL, alone or in combination with probiotic strains (potential synbiotics), in vitro experiments were conducted on stool from healthy, IBS, and ulcerative colitis adult donors. In anaerobic batch culture fermenters, Bifidobacterium and Eubacterium rectale-Clostridium coccoides counts, and short-chain fatty acids (SCFAs) including butyrate increased during fermentation with 2′-FL and some of the 2′-FL/probiotic combinations. In a subsequent open-label pilot trial, the effect of a 2′-FL-containing nutritional formula was evaluated in twelve adults with IBS or ulcerative colitis. Gastrointestinal Quality of Life Index (GIQLI) total and gastrointestinal symptoms domain scores, stool counts of Bifidobacterium and Faecalibacterium prausnitzii, and stool SCFAs including butyrate, increased after six weeks of intervention. Consistent with documented effects of 2′-FL, the batch culture fermentation experiments demonstrated bifidogenic and butyrogenic effects of 2′-FL during fermentation with human stool samples. Consumption of the 2′-FL-containing nutritional formula by adults with IBS or ulcerative colitis was associated with improvements in intra- and extra-intestinal symptoms, and bifidogenic and butyrogenic effects.

Relationships of gut microbiota, short-chain fatty acids, inflammation, and the gut barrier in Parkinson\u2019s disease

BackgroundPrevious studies have reported that gut microbiota, permeability, short-chain fatty acids (SCFAs), and inflammation are altered in Parkinson’s disease (PD), but how these factors are linked and how they contribute to disease processes and symptoms remains uncertain. This study sought to compare and identify associations among these factors in PD patients and controls to elucidate their interrelations and links to clinical manifestations of PD.MethodsStool and plasma samples and clinical data were collected from 55 PD patients and 56 controls. Levels of stool SCFAs and stool and plasma inflammatory and permeability markers were compared between patients and controls and related to one another and to the gut microbiota.ResultsCalprotectin was increased and SCFAs decreased in stool in PD in a sex-dependent manner. Inflammatory markers in plasma and stool were neither intercorrelated nor strongly associated with SCFA levels. Age at PD onset was positively correlated with SCFAs and negatively correlated with CXCL8 and IL-1β in stool. Fecal zonulin correlated positively with fecal NGAL and negatively with PD motor and non-motor symptoms. Microbiota diversity and composition were linked to levels of SCFAs, inflammatory factors, and zonulin in stool. Certain relationships differed between patients and controls and by sex.ConclusionsIntestinal inflammatory responses and reductions in fecal SCFAs occur in PD, are related to the microbiota and to disease onset, and are not reflected in plasma inflammatory profiles. Some of these relationships are distinct in PD and are sex-dependent. This study revealed potential alterations in microbiota-host interactions and links between earlier PD onset and intestinal inflammatory responses and reduced SCFA levels, highlighting candidate molecules and pathways which may contribute to PD pathogenesis and clinical presentation and which warrant further investigation.

Профилактика дисбиотических нарушений и антибиотик- ассоциированной диареи у детей с острыми респираторными заболеваниями на фоне антибиотикотерапии

Aim: to develop a method of dysbiotic abnormality prevention after antibiotic therapy (ABT) in early childhood. Patients and Methods: the study enrolled 90 children aged 12–60 months who were admitted to the hospital with complicated acute respiratory infections (ARIs) and received ABT. The children were randomized into three groups (each comprised of 30 children). The children received either a probiotic with Lactobacillus rhamnosus GG and Bifidobacterium BB-12 (group 1) or a cytomucoprotector, gelatin tannate (group 2) to prevent antibiotic-associated diarrhea (AAD). Group 3 children received ABT only. To assess microbiocenosis, short-chain fatty acids (SCFAs) in stool were measured by gas-liquid chromatography. Results: AAD was reported in 23.3% of group 1 children, 17% of group 2 children, and 46.7% of group 3 children (p=0.03). In group 2, the duration of diarrhea was significantly lower. Baseline stool concentration of SCFAs was 2.5-times lower compared to normal ranges. Further reduction in the total absolute level of SCFAs was reported in group 3 after treatment. An increase in total SCFA level, a significant increase in the relative amounts of acetic acid, and a reduction in propionic acid and (to a lesser degree) butyric acid were reported in groups 1 and 2 compared to group 3. Conclusions: an improvement in stool SCFA levels was reported in group 1 and 2 children who received probiotics or cytomucoprotector. Incorporation of these medications and ABT in the complex treatment for ARIs in children stabilized metabolic activity of microbiota through preserving the pool of indigenous microorganisms producing butyrate. KEYWORDS: antibiotic, antibiotic-associated diarrhea, acute respiratory viral infections, microbiota, short-chain fatty acids, probiotic, gelatin tannate. FOR CITATION: Mazankova L.N., Perlovskaya S.G., Ardatskaya M.D. et al. Prevention of dysbiosis and antibiotic-associated diarrhea in children with acute respiratory infections after antibiotic therapy. Russian Medical Inquiry. 2021;5(11):712–720 (in Russ.). DOI: 10.32364/2587-6821-2021-5-11-712-720.

Nopal fiber (Opuntia ficus-indica) improves symptoms in irritable bowel syndrome in the short term: a randomized controlled trial.

Clinical guidelines provide limited and conflicting recommendations regarding dietary fiber supplementation in irritable bowel syndrome (IBS). Nopal (Opuntia ficus-indica) is a cactus plant fiber containing both insoluble and soluble fibers that may have therapeutic potential in IBS. Our aim was to evaluate the dose-response effect of extracted nopal fiber powder on symptoms in IBS. We performed a 4-arm, double-blind, parallel, randomized controlled trial in 60 patients fulfilling Rome IV criteria for IBS. Patients were randomized and blindly allocated to receive either nopal fiber (10, 20, or 30g/day) or placebo (30g/day dextrose) for one week and to keep their usual diet. Symptom severity (Global Symptom Question, IBS-SSS, Gastrointestinal Symptom Rating Scale), stool frequency and consistency (Bristol Stool Form Scale), breath hydrogen response, and stool short-chain fatty acids (SCFA) were measured at baseline and follow-up. Significantly more patients reported adequate relief of symptoms after 20g/day (87%, p=0.008) and 30g/day (80%, p=0.025) of nopal fiber compared to placebo (33%). More patients receiving 20g/day nopal fiber (67%) had a>50% reduction in IBS-SSS compared to placebo (20%, p=0.027), whereas the 30g/day dose induced more loose stools (p=0.027). Response rates were similar among IBS subtypes. There were no differences in breath hydrogen or stool SCFA between groups. Nopal fiber supplementation at doses of 20 and 30g/day was associated with short-term improvement in IBS symptoms, warranting a fully powered clinical trial of longer duration with symptomatic, physiological, and microbiological endpoints.

4033 Evaluating the Effect of Prebiotics on the Gut Microbiome Profile and Beta-cell Function in Newly-Diagnosed Type 1 Diabetes

OBJECTIVES/GOALS: Type 1 diabetes (T1D) results from the autoimmune destruction of insulin-producing β-cells. Emerging data suggest that differences in intestinal microbiota might be critically involved both in autoimmunity and in glucose homeostasis. The prebiotic high amylose maize starch (HAMS) alters the gut microbiome profile and metabolites positively by increasing production of beneficial short chain fatty acids (SCFAs) that have significant anti-inflammatory effects. HAMS also improves glycemia, insulin sensitivity and secretion in healthy non-diabetic adults. Further, an acetylated and butyrylated form of HAMS (HAMS-AB) that increases beneficial SCFA production, namely acetate and butyrate, has been safe and effective in disease prevention in mouse T1D models. The objective of the proposed study is to assess the effect of administering a prebiotic, such as HAMS-AB, on the gut microbiome profile, SCFA production, glycemia and β-cell function in humans with T1D. METHODS/STUDY POPULATION: We hypothesize that administration of HAMS-AB will (i) improve the gut microbiome profile in humans with T1D, (ii) increase SCFA production, and (iii) improve β-cell health, β-cell function and overall glycemia. We propose a pilot randomized controlled cross-over trial of HAMS-AB in 12 youth with newly-diagnosed T1D. We will use state-of-the-art markers to profile the gut microbiome (using 16S rRNA sequencing), measure stool SCFA levels (using gas chromatography), asses β-cell stress/death (by measuring proinsulin to C-peptide ratios) and glycemia (assessed by continuous glucose monitoring and HbA1c measurements). RESULTS/ANTICIPATED RESULTS: We expect that the use of HAMS-AB in newly diagnosed youth with type 1 diabetes will alter the gut microbiome profile (thus increasing the number of fermenters and SCFA levels), β-cell function and glycemia in humans with T1D. DISCUSSION/SIGNIFICANCE OF IMPACT: Given the unknown long-term effects of immune-modulatory therapy on those at risk for or those diagnosed with T1D, the use of a prebiotic such as HAMS-AB offers a simple, safe, yet inexpensive and tolerated dietary alternative approach to mitigating disease.

Gut microbiota in neonates with congenital gastrointestinal surgical conditions: a prospective study.

BackgroundThere is limited information on gut microbiota of neonates with congenital gastrointestinal surgical conditions (CGISCs) available.MethodsThis study compared stool microbiota and short-chain fatty acids (SCFAs) of 37 term infants with CGISCs with 36 term healthy infants (HIs). Two stool samples were collected from each infant: as soon as possible after birth (week 1) and 10–14 days of life (week 2).ResultsBacterial richness and alpha diversity were comparable between CGISCs and HIs at week 1 and week 2 (all p > 0.05). Beta diversity analysis revealed that at week 1, CGISCs had similar community structures to HIs (p = 0.415). However, by week 2, community structures of CGISCs were significantly different from HIs (p = 0.003). At week 1, there were no significant differences in the relative abundances of genera Bifidobacterium and Bacteroides between CGISCs and HIs. At week 2, the relative abundance of Bifidobacterium was significantly lower in CGISCs (mean percentage 7.21 ± 13.49 vs. 28.96 ± 19.6; p = 0.002). Bacteroides were also less abundant in the CGISC group (mean percentage 0.12 ± 0.49 vs. 6.59 ± 8.62; p = 0.039). Relative abundance of genera Pseudomonas and Escherichia–Shigella were higher in CGISCs. At week 2, stool concentrations of all SCFAs were lower in CGISCs (all p < 0.001).ConclusionsDuring hospitalization, neonates with CGISCs develop gut dysbiosis and deficiency of SCFAs.Impact During hospitalisation, neonates with congenital gastrointestinal surgical conditions develop gut dysbiosis with deficiency of Bifidobacteria and Bacteroides and increased abundance of Escherichia-Shigella and Pseudomonas. They also have low levels of short chain fatty acids in their stools compared to healthy infants.This is the first study evaluating the gut microbiota using 16S ribosomal RNA sequencing methods and stool short chain fatty acids in neonates with congenital gastrointestinal surgical conditions and comparing them to healthy infants.The findings of this study will pave the way for randomised trials of bifidobacterial supplementation in neonates with congenital gastrointestinal surgical conditions.

Stool Short-Chain Fatty Acids in Critically Ill Patients with Sepsis

Objective: To determine the concentration of stool short-chain fatty acids (SCFAs) in critically ill patients with sepsis and to compare the results between the critically ill patient and the control group.Methods: This descriptive, multicenter, observational study was conducted in five health institutions. Over a 6-month study period, critically ill patients with sepsis who were admitted to the intensive care unit (ICU) and met the inclusion criteria were enrolled, and a control, paired by age and sex, was recruited for each patient. A spontaneous stool sample was collected from each participant and a gas chromatograph coupled to a mass spectrometer (Agilent 7890/MSD 5975 C) was used to measure the concentrations SCFAs.Results: The final sample included 44 patients and 45 controls. There were no differences in the age and sex distributions between the groups (p > 0.05). According to body mass index (BMI), undernutrition was more prevalent among critically ill patients, and BMI in control subjects was most frequently classified as overweight (p = 0.024). Propionic acid, acetic acid, butyric acid, and isobutyric acid concentrations were significantly lower in the critically ill patient group than in the control group (p = 0.000). No association with outcome variables (complications, ICU stay, and discharge condition) was found in the patients, and patients diagnosed with infection on ICU admission showed significant decreases in butyric and isobutyric acid concentrations with respect to other diagnostic criteria (p < 0.05).Conclusions: The results confirm significantly lower concentrations of stool SCFAs in critically ill patients with sepsis than in control subjects. Due to its role in intestinal integrity, barrier function, and anti-inflammatory effect, maintaining the concentration of SCFAs may be important in the ICU care protocols of the critical patient.

Gut microbiota, short chain fatty acids, and obesity across the epidemiologic transition: the METS-Microbiome study protocol

BackgroundWhile some of the variance observed in adiposity and weight change within populations can be accounted for by traditional risk factors, a new factor, the gut microbiota, has recently been associated with obesity. However, the causal mechanisms through which the gut microbiota and its metabolites, short chain fatty acids (SCFAs) influence obesity are unknown, as are the individual obesogenic effects of the individual SCFAs (butyrate, acetate and propionate). This study, METS-Microbiome, proposes to examine the influence of novel risk factors, the gut microbiota and SCFAs, on obesity, adiposity and weight change in an international established cohort spanning the epidemiologic transition.MethodsThe parent study; Modeling the Epidemiologic Transition Study (METS) is a well-established and ongoing prospective cohort study designed to assess the association between body composition, physical activity, and relative weight, weight gain and cardiometabolic disease risk in five diverse population-based samples in 2500 people of African descent. The cohort has been prospectively followed since 2009. Annual measures of obesity risk factors, including body composition, objectively measured physical activity and dietary intake, components which vary across the spectrum of social and economic development. In our new study; METS-Microbiome, in addition to continuing yearly measures of obesity risk, we will also measure gut microbiota and stool SCFAs in all contactable participants, and follow participants for a further 3 years, thus providing one of the largest gut microbiota population-based studies to date.DiscussionThis new study capitalizes upon an existing, extensively well described cohort of adults of African-origin, with significant variability as a result of the widespread geographic distributions, and therefore variation in the environmental covariate exposures. The METS-Microbiome study will substantially advance the understanding of the role gut microbiota and SCFAs play in the development of obesity and provide novel obesity therapeutic targets targeting SCFAs producing features of the gut microbiota.Trial registrationRegistered NCT03378765 Date first posted: December 20, 2017.

Relating Stool Microbial Metabolite Levels, Inflammatory Markers and Dietary Behaviors to Screening Colonoscopy Findings in a Racially/Ethnically Diverse Patient Population.

Colorectal cancer (CRC) is the third leading cause of cancer death for both men and women in the United States, yet it is treatable and preventable. African Americans have higher incidence of CRC than other racial/ethnic groups, however, it is unclear whether this disparity is primarily due to environmental or biological factors. Short chain fatty acids (SCFAs) are metabolites produced by bacteria in the colon and are known to be inversely related to CRC progression. The aim of this study is to investigate how stool SCFA levels, markers of inflammation in stool and dietary intake relate to colonoscopy findings in a diverse patient population. Stool samples from forty-eight participants were analyzed for SCFA levels and inflammatory markers (lysozyme, secretory IgA, lactoferrin). Additionally, participants completed the National Cancer Institute’s Diet History Questionnaire II (DHQ II) to report dietary intake over the past year. Subsequently, the majority of participants underwent screening colonoscopy. Our results showed that African Americans had higher total levels of SCFAs in stool than other racial/ethnic groups, significantly lower intake of non-starchy vegetables and similar inflammatory marker expression and colonoscopy outcomes, compared to others. This work is an initial exploration into the biological and clinical factors that may ultimately inform personalized screening approaches and clinical decision-making to improve colorectal cancer disparities for African Americans.

Alcohol Feeding in Mice Promotes Colonic Hyperpermeability and Changes in Colonic Organoid Stem Cell Fate

Alcohol increases intestinal permeability to proinflammatory microbial products that promote liver disease, even after a period of sobriety. We sought to test the hypothesis that alcohol affects intestinal stem cells using an invivo model and exvivo organoids generated from jejunum and colon from mice fed chronic alcohol. Mice were fed a control or an alcohol diet. Intestinal permeability, liver steatosis-inflammation, and stool short-chain fatty acids (SCFAs) were measured. Jejunum and colonic organoids and tissue were stained for stem cell, cell lineage, and apical junction markers with assessment of mRNA by PCR and RNA-seq. ChIP-PCR analysis was carried out for Notch1 using an antibody specific for acetylated histone 3. Alcohol-fed mice exhibited colonic (but not small intestinal) hyperpermeability, steatohepatitis, and decreased butyrate/total SCFA ratio in stool. Stem cell, cell lineage, and apical junction marker staining in tissue or organoids from jejunum tissue were not impacted by alcohol. Only chromogranin A (Chga) was increased in jejunum organoids by qPCR. However, colonic tissue and organoid staining exhibited an alcohol-induced significant decrease in cytokeratin 20+ (Krt20+) absorptive lineage enterocytes, a decrease in occludin and E-cadherin apical junction proteins, an increase in Chga, and an increase in the Lgr5 stem cell marker. qPCR revealed an alcohol-induced decrease in colonic organoid and tissue Notch1, Hes1, and Krt20 and increased Chga, supporting an alteration in stem cell fate due to decreased Notch1 expression. Colonic tissue ChIP-PCR revealed alcohol feeding suppressed Notch1 mRNA expression (via deacetylation of histone H3) and decreased Notch1 tissue staining. Data support a model for alcohol-induced colonic hyperpermeability via epigenetic effects on Notch1, and thus Hes1, suppression through a mechanism involving histone H3 deacetylation at the Notch1 locus. This decreased enterocyte and increased enteroendocrine cell colonic stem cell fate and decreased apical junctional proteins leading to hyperpermeability.