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.

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Short Chain Fatty Acid Production from Mycoprotein and Mycoprotein Fibre in an In Vitro Fermentation Model

Nutrients ◽

10.3390/nu11040800 ◽

2019 ◽

Vol 11 (4) ◽

pp. 800 ◽

Cited By ~ 5

Author(s):

Hannah Harris ◽

Christine Edwards ◽

Douglas Morrison

Keyword(s):

Energy Intake ◽

Short Chain Fatty Acid ◽

Short Chain Fatty Acids ◽

Chain Fatty Acid ◽

Fibre Content ◽

Short Chain ◽

Fatty Acid Production ◽

In Vitro Fermentation ◽

Fermentation Model

Dietary mycoprotein (marketed as QuornTM) has many health benefits, including reductions in energy intake. The majority of studies evaluating mycoprotein focus on the protein content and very few consider the fibre content. Fibre consumption is also associated with decreased energy intake, which is partly attributed to short chain fatty acids (SCFAs) from fibre fermentation by colonic bacteria. To study the SCFA-producing capability of mycoprotein, in vitro batch fermentations were conducted, and SCFA production compared with that from extracted mycoprotein fibre, oligofructose (OF), rhamnose, and laminarin. Mycoprotein and mycoprotein fibre were both fermentable, resulting in a total SCFA production of 24.9 (1.7) and 61.2 (15.7) mmol/L, respectively. OF led to a significantly higher proportion of acetate compared to all other substrates tested (92.6 (2.8)%, p < 0.01). Rhamnose generated the highest proportion of propionate (45.3 (2.0)%, p < 0.01), although mycoprotein and mycoprotein fibre yielded a higher proportion of propionate compared with OF and laminarin. Butyrate proportion was the highest with laminarin (28.0 (10.0)although mycoprotein fibre led to a significantly higher proportion than OF (p < 0.01). Mycoprotein is a valuable source of dietary protein, but its fibre content is also of interest. Further evaluation of the potential roles of the fibre content of mycoprotein is required.

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Effect of β-Glucan and Black Tea in a Functional Bread on Short Chain Fatty Acid Production by the Gut Microbiota in a Gut Digestion/Fermentation Model

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph16020227 ◽

2019 ◽

Vol 16 (2) ◽

pp. 227 ◽

Cited By ~ 1

Author(s):

Abbe Mhd Jalil ◽

Emilie Combet ◽

Christine Edwards ◽

Ada Garcia

Keyword(s):

Black Tea ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Colonic Fermentation ◽

Fatty Acid Production ◽

Total Polyphenol ◽

In Vitro System ◽

Functional Bread ◽

Fermentation Model

β-Glucan and black tea are fermented by the colonic microbiota producing short chain fatty acids (SCFA) and phenolic acids (PA). We hypothesized that the addition of β-glucan, a dietary fiber, and tea polyphenols to a food matrix like bread will also affect starch digestion in the upper gut and thus further influence colonic fermentation and SCFA production. This study investigated SCFA and PA production from locally developed breads: white bread (WB), black tea bread (BT), β-glucan bread (βG), β-glucan plus black tea bread (βGBT). Each bread was incubated in an in vitro system mimicking human digestion and colonic fermentation. Digestion with α-amylase significantly (p = 0.0001) increased total polyphenol and polyphenolic metabolites from BT bread compared with WB, βG, and βGBT. Total polyphenols in βGBT remained higher (p = 0.016; 1.3-fold) after digestion with pepsin and pancreatin compared with WB. Fermentations containing βG and βGBT produced similar propionate concentrations ranging from 17.5 to 18.6 mmol/L and total SCFA from 46.0 to 48.9 mmol/L compared with control WB (14.0 and 37.4 mmol/L, respectively). This study suggests that combination of black tea with β-glucan in this functional bread did not impact on SCFA production. A higher dose of black tea and β-glucan or in combination with other fibers may be needed to increase SCFA production.

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Cross-Talk Between Butyric Acid and Gut Microbiota in Ulcerative Colitis Following Fecal Microbiota Transplantation

Frontiers in Microbiology ◽

10.3389/fmicb.2021.658292 ◽

2021 ◽

Vol 12 ◽

Author(s):

Hao-Ming Xu ◽

Hong-Li Huang ◽

Jing Xu ◽

Jie He ◽

Chong Zhao ◽

...

Keyword(s):

Ulcerative Colitis ◽

Gut Microbiota ◽

Butyric Acid ◽

Fecal Microbiota Transplantation ◽

Short Chain Fatty Acids ◽

Fecal Microbiota ◽

16S Sequencing ◽

Α Diversity ◽

The Impact

Fecal microbiota transplantation (FMT) can inhibit the progression of ulcerative colitis (UC). However, how FMT modulates the gut microbiota and which biomarker is valuable for evaluating the efficacy of FMT have not been clarified. This study aimed to determine the changes in the gut microbiota and their relationship with butyric acid following FMT for UC. Fecal microbiota (FM) was isolated from healthy individuals or mice and transplanted into 12 UC patients or colitis mice induced by dextran sulfate sodium (DSS). Their clinical colitis severities were monitored. Their gut microbiota were analyzed by 16S sequencing and bioinformatics. The levels of fecal short-chain fatty acids (SCFAs) from five UC patients with recurrent symptoms after FMT and individual mice were quantified by liquid chromatography–mass spectrometry (LC–MS). The impact of butyric acid on the abundance and diversity of the gut microbiota was tested in vitro. The effect of the combination of butyric acid-producing bacterium and FMT on the clinical responses of 45 UC patients was retrospectively analyzed. Compared with that in the controls, the FMT significantly increased the abundance of butyric acid-producing bacteria and fecal butyric acid levels in UC patients. The FMT significantly increased the α-diversity, changed gut microbial structure, and elevated fecal butyric acid levels in colitis mice. Anaerobic culture with butyrate significantly increased the α-diversity of the gut microbiota from colitis mice and changed their structure. FMT combination with Clostridium butyricum-containing probiotics significantly prolonged the UC remission in the clinic. Therefore, fecal butyric acid level may be a biomarker for evaluating the efficacy of FMT for UC, and addition of butyrate-producing bacteria may prolong the therapeutic effect of FMT on UC by changing the gut microbiota.

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P871 Successful detection of dysbiosis and altered short-chain-fatty acids levels in in vitro colonic microbiota culture system using faecal samples of ulcerative colitis

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjx180.998 ◽

2018 ◽

Vol 12 (supplement_1) ◽

pp. S557-S558

Author(s):

J Inoue ◽

K Sasaki ◽

N Hoshi ◽

D Sasaki ◽

A Kondo ◽

...

Keyword(s):

Ulcerative Colitis ◽

Fatty Acids ◽

Culture System ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Colonic Microbiota ◽

Faecal Samples ◽

Chain Fatty Acids

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P492 The UC Diet and Antibiotics for Treatment of Mild to Moderate Pediatric Ulcerative Colitis: A prospective open label pilot study

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab076.615 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S476-S477

Author(s):

C Sarbagili Shabat ◽

L Albenberg ◽

J Van Limbergen ◽

A Otley ◽

M Yaakov ◽

...

Keyword(s):

Ulcerative Colitis ◽

Pilot Study ◽

Clinical Remission ◽

Activity Index ◽

Pilot Trial ◽

Open Label ◽

Intention To Treat ◽

Alternative Therapeutic Approach ◽

Stable Maintenance ◽

Steroid Sparing

Abstract Background Strategies that target the microbiome may offer an alternative therapeutic approach for Ulcerative Colitis (UC). The goal of the pilot trial was to evaluate the efficacy of a novel microbe-directed UC diet (UCD) for clinical remission, as well as use of antibiotics for dietary refractory patients as an alternative strategy for remission. Methods This was a prospective, single arm, open label, pilot study in patients aged 8–19, with a pediatric UC activity index (PUCAI) scores >10 on stable maintenance therapy. Patients failing to enter remission (PUCAI<10) on diet could receive a 14-day course of Amoxycillin, Metronidazole and Doxycycline (AMD), and were re-assessed on day 21. The primary endpoint was intention to treat (ITT) remission at week 6 with UCD. Results Twenty-four UCD treatment courses were given to 23 eligible children (mean age 15.3±2.9 years). Median PUCAI decreased from baseline 35 (30–40) to 12.5 (5–27.5) week 6 (P=0.001). Clinical remission with UCD alone was achieved in 9/24 (37.5%). Median calprotectin declined from baseline 818 (630.0–1880.0) to 592.0 (140.7–902.4) week 6. Eight patients received treatment with antibiotics after failing diet, 4/8 (50.0%) subsequently entered remission 3 weeks later. Conclusion The UC Diet appears to be effective for induction of remission in children with mild to moderate UC suggesting that diet could play a role in the disease. Sequential use of UCD followed by antibiotic therapy needs to be evaluated as a microbiome targeted steroid sparing strategy.

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Dietary Fibres Differentially Impact on the Production of Phenolic Acids from Rutin in an In Vitro Fermentation Model of the Human Gut Microbiota

Nutrients ◽

10.3390/nu12061577 ◽

2020 ◽

Vol 12 (6) ◽

pp. 1577 ◽

Cited By ~ 3

Author(s):

Jaroslav Havlik ◽

Vittoria Marinello ◽

Andrew Gardyne ◽

Min Hou ◽

William Mullen ◽

...

Keyword(s):

Propionic Acid ◽

Phenolic Acids ◽

Wheat Bran ◽

Short Chain Fatty Acids ◽

Phenolic Metabolites ◽

Dietary Fibres ◽

Fermentation Model ◽

Hydroxyphenylacetic Acid ◽

The Impact

Polyphenols are often ingested alongside dietary fibres. They are both catabolised by, and may influence, the intestinal microbiota; yet, interactions between them and the impact on their resultant microbial products are poorly understood. Dietary fibres (inulin, pectin, psyllium, pyrodextrin, wheat bran, cellulose—three doses) were fermented in vitro with human faeces (n = 10) with and without rutin (20 µg/mL), a common dietary flavonol glycoside. Twenty-eight phenolic metabolites and short chain fatty acids (SCFA) were measured over 24 h. Several phenolic metabolites were produced during fibre fermentation, without rutin. With rutin, 3,4-dihydroxyphenylacetic acid (3,4diOHPAA), 3-hydroxyphenylacetic acid (3OHPAA), 3-(3 hydroxyphenyl)propionic acid (3OHPPA) and 3-(3,4-dihydroxyphenyl)propionic acid (3,4diOHPPA; DOPAC) were produced, with 3,4diOHPAA the most abundant, confirmed by fermentation of 13C labelled quercetin. The addition of inulin, wheat bran or pyrodextrin increased 3,4diOHPAA 2 2.5-fold over 24 h (p < 0.05). Rutin affected SCFA production, but this depended on fibre, fibre concentration and timepoint. With inulin, rutin increased pH at 6 h from 4.9 to 5.6 (p = 0.01) but increased propionic, butyric and isovaleric acid (1.9, 1.6 and 5-fold, p < 0.05 at 24 h). Interactions between fibre and phenolics modify production of phenolic acids and SCFA and may be key in enhancing health benefits.

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A Novel UC Exclusion Diet and Antibiotics for Treatment of Mild to Moderate Pediatric Ulcerative Colitis: A Prospective Open-Label Pilot Study

Nutrients ◽

10.3390/nu13113736 ◽

2021 ◽

Vol 13 (11) ◽

pp. 3736

Author(s):

Chen Sarbagili-Shabat ◽

Lindsey Albenberg ◽

Johan Van Limbergen ◽

Naomi Pressman ◽

Anthony Otley ◽

...

Keyword(s):

Ulcerative Colitis ◽

Pilot Study ◽

Clinical Remission ◽

Activity Index ◽

Pilot Trial ◽

Fecal Calprotectin ◽

Open Label ◽

Intention To Treat ◽

Exclusion Diet ◽

Stable Maintenance

Background: As the microbiome plays an important role in instigating inflammation in ulcerative colitis (UC), strategies targeting the microbiome may offer an alternative therapeutic approach. The goal of the pilot trial was to evaluate the potential efficacy and feasibility of a novel UC exclusion diet (UCED) for clinical remission, as well as the potential of sequential antibiotics for diet-refractory patients to achieve remission without steroids. Methods: This was a prospective, single-arm, multicenter, open-label pilot study in patients aged 8–19, with pediatric UC activity index (PUCAI) scores >10 on stable maintenance therapy. Patients failing to enter remission (PUCAI < 10) on the diet could receive a 14-day course of amoxycillin, metronidazole and doxycycline (AMD), and were re-assessed on day 21. The primary endpoint was intention-to-treat (ITT) remission at week 6, with UCED as the only intervention. Results: Twenty-four UCED treatment courses were given to 23 eligible children (mean age: 15.3 ± 2.9 years). The median PUCAI decreased from 35 (30–40) at baseline to 12.5 (5–30) at week 6 (p = 0.001). Clinical remission with UCED alone was achieved in 9/24 (37.5%). The median fecal calprotectin declined from 818 (630.0–1880.0) μg/g at baseline to 592.0 (140.7–1555.0) μg/g at week 6 (p > 0.05). Eight patients received treatment with antibiotics after failing on the diet; 4/8 (50.0%) subsequently entered remission 3 weeks later. Conclusion: The UCED appears to be effective and feasible for the induction of remission in children with mild to moderate UC. The sequential use of UCED followed by antibiotic therapy needs to be evaluated as a microbiome-targeted, steroid-sparing strategy.

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Capsular Polysaccharide From Bacteroides fragilis Protects Against Ulcerative Colitis in an Undegraded Form

Frontiers in Pharmacology ◽

10.3389/fphar.2020.570476 ◽

2020 ◽

Vol 11 ◽

Author(s):

Lijun Zheng ◽

Meihua Luo ◽

Gaobo Kuang ◽

Yangyang Liu ◽

Debao Liang ◽

...

Keyword(s):

Ulcerative Colitis ◽

Capsular Polysaccharide ◽

Intestinal Flora ◽

Bacteroides Fragilis ◽

Fluorescein Isothiocyanate ◽

Optimal Dose ◽

Short Chain Fatty Acids ◽

Underlying Mechanism ◽

Fecal Microbiota

The prominent human symbiont Bacteroides fragilis protects animals from intestinal diseases, such as ulcerative colitis, and its capsular polysaccharide plays a key role in reducing inflammation. B. fragilis strain ZY-312 was isolated from the feces of a healthy breast-fed infant, and the zwitterionic capsular polysaccharide zwitterionic polysaccharide, TP2, was extracted. In rats with 2,4-dinitrobenzenesulfonic acid (DNBS)-induced enteritis, TP2 at an optimal dose of 2.5 mg/kg could significantly alleviate enteritis and reduced the degree of intestinal adhesions, the intestinal ulcer area, and the incidence of ulcers in rats. To understand the underlying mechanism, TP2 was labeled with Fluorescein isothiocyanate and orally administered at a dose of 2.5 mg/kg in rats. TP2 was mainly distributed in the cecum and colorectum, but it was not detected in the blood and other organs except that a compound with a molecular weight greater than that of TP2-FITC was found in liver tissue. During the absorption, distribution, metabolism, and excretion, TP2 was indigestible. These results were further confirmed by investigation in the simulated gastric, intestinal fluid, and colonic fluid with fecal microbiota in vitro, where TP2 remained unaltered at different time points. Furthermore, flora composition was analyzed in simulated colonic fluid with TP2 added and it was found that TP2 increased the abundance of Faecalibacterium, Enterococcus romboutsia, and Ruminococcaceae, whereas the abundance of the phylum Proteobacteria represented by Sutterella, Desulfovibrio, and Enterobacteriaceae was decreased. However, the amount of short-chain fatty acids in the simulated colonic fluid was not changed by intestinal flora post-TP2 addition. In conclusion, these findings confirmed that TP2, a capsular polysaccharide of B. fragilis, protects against ulcerative colitis in an undegraded form.

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Effect of xylitol on gut microbiota in an in vitro colonic simulation

Turkish Journal of Biochemistry ◽

10.1515/tjb-2018-0328 ◽

2019 ◽

Vol 44 (5) ◽

pp. 646-653

Author(s):

Yuanyuan Xu ◽

Yi Chen ◽

Shasha Xiang ◽

Kun Ye ◽

Xuan Bao ◽

...

Keyword(s):

Gut Microbiota ◽

Continuous Fermentation ◽

Daily Intake ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Protective Agent ◽

Fermentation Model ◽

Population Sizes ◽

Gut Microbiota Composition

Abstract Objective Xylitol has been commonly used as a sweetener and dental caries protective agent. However, how xylitol influences the composition and metabolism of gut microbiota is not known yet. This study aimed to dissect the changes of microbiota and their metabolites under xylitol supplementation in an in vitro colonic simulation. Materials and methods A single-phase continuous fermentation model was used to culture human fecal flora and the 16s rDNA and short chain fatty acid were analyzed. Results and discussion It was found that gut microbiota composition differentiated after xylitol supplementation only for the beginning 3 days. Xylitol significantly enhanced the relative amount of butyrate synthesizing bacteria such as Clostridium and Phascolarctobacterium. Meanwhile, xylitol increased the production of propionic acid and butyrate. An increase of Escherichia population sizes after xylitol supplementation was beyond expectation. By Spearman analysis, a positive relationship between Escherichia and Bifidobacterium was found. Conclusion xylitol can rapidly enhance the total amount of short chain fatty acids, but its influence will disappear after 3 days of fermentation. Results of this investigation can be a guideline for the further investigations on xylitol in relation to gut microbiota and the daily intake determinations.

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