Fermentable Fiber Research Articles

A47 MICROBIAL FUNCTIONS AS BIOMARKERS OF PRO-INFLAMMATORY RESPONSE TO SELECT DIETARY FIBERS IN IBD

BackgroundDietary fibers are not digested in the bowel; they are fermented by microbes, typically promoting gut health. However, IBD patients experience sensitivity to consumption of fibers. Our previous findings offered the first mechanistic evidence demonstrating that unfermented dietary β-fructans (inulin and FOS) can induce pro-inflammatory cytokines in a subset of pediatric IBD colonic biopsies cultured ex vivo, and in the SYNERGY-1 (β-fructan) clinical study of adult remission UC patients. Incubating FOS with whole-microbiota intestinal washes from non-IBD or remission IBD patients improved fermentation and reduced pro-inflammatory responses, but not from patients with active disease. Fibre-induced immune responses correlated with microbe functions, luminal metabolites, and fibre avoidance.AimsHere we aimed to expand on our findings and define the role of microbial functions in mediating host response to β-fructans.MethodsColonic biopsies cultured ex vivo and cell lines in vitro were incubated with FOS (5g/L), or fermentation supernatants (24hr anaerobic fermentation). Immune responses (cytokine secretion [ELISA/MSD] and expression [qPCR]) were assessed. Taxonomic classification of microbial fermentation cultures was conducted with Kraken2 and metabolic profiling by HUMAnN2. HPLC and gas chromatography volatile fatty acid (CG-VFA) analysis were used to identify concentrations of remaining fibre and SCFAs following anaerobic fermentation.Results7 microbial enzymes were identified to be predictive of cytokine (IL-1β, IL23, IL-5, IL-8, MIP-1α) secretion in ex vivo colonic biopsies from pediatric Crohn disease (CD; n=38), ulcerative colitis (UC; n=20), and non-IBD (n=21) patients, in response to β-fructans; their use as biomarkers of response was determined in patient stool from the SYNERGY-1 clinical study cohort. Fermentation of FOS by whole-microbe intestinal washes from only non-IBD or remission IBD patients reduced cytokine secretion, and our findings demonstrate that this was due to a combination of reduction of β-fructan present and production of a precise combination of anti-inflammatory SCFAs.ConclusionsOur findings suggest that intolerance and avoidance of fibers in select IBD patients is associated with the inability to ferment these fibers, mediated by altered microbial functions (enzymes), leading to worsened inflammation. Data indicate that gut microbial function, not composition, predicts patient pro-inflammatory response to β-fructans, supporting our hypothesis that overall community function impacts fibre fermentation and affects associated pro-inflammatory effects. Our work highlights select disease state scenarios in which administration of fermentable fibers should be avoided and tailored dietary interventions considered.Funding AgenciesCIHRWeston Foundation, Mitacs

A228 A FERMENTABLE FIBRE FREE DIET ACCELERATES SPONTANEOUS COLITIS DEVELOPMENT AND ALTERS THE GUT MICROBIOME IN MUC2-/- MICE

Abstract Background A key feature of ulcerative colitis (UC) is a defective colonic mucus layer. As Muc2-/- mice lack intestinal mucus, they’re often used to model UC. In these mice, luminal bacteria translocate from the gut lumen, triggering spontaneous colitis by 12–16 weeks of age. Notably, mucus defects are also seen in wildtype mice fed a fermentable fibre free (FF-free) diet. Aside from thinner mucus, FF-free fed mice show increased susceptibility to bacterial infections and a microbiome shift from fibre-utilizing to mucus-degrading bacteria. Indeed, a recent clinical study found that a microbiome shift towards proteolytic bacteria preceded clinical diagnosis of UC Aims To determine whether feeding newly weaned Muc2-/- mice a FF-free versus chow or inulin-enriched diet leads to - more rapid development of spontaneous colitis - shifts in the gut microbiota towards protein fermentation Methods Newly weaned Muc2-/- mice (3–4 weeks old) were fed 1 of 3 diets: 1) usual chow (Chow; 14.7% fibre mix), 2) FF-free (10% cellulose – poorly fermented) and 3) inulin-enriched (IN; same nutritional content as FF-free, with 10% inulin instead of cellulose). Body weight, diet intake and disease activity were monitored daily. By day 10, mice in the FF-free group developed severe colitis requiring euthanization. At this time, cecal contents (short-chain fatty acid [SCFA] analysis) and colonic tissue from all mice were collected for alcian blue/PAS staining and histopathological scoring. Stool was collected for 16S rRNA sequencing Results FF-free fed mice consumed fewer calories (p=0.0073), experienced less body weight gain (p=0.002), had colonic shortening (p<0.0001) and higher disease activity scores (p<0.0001) than mice fed the IN diet. Histopathological scores were higher in FF-free versus Chow (p<0.0001) and IN (p<0.0001) fed mice. Goblet cell mucin staining was reduced in FF-free compared to Chow and IN fed mice. Beta-diversity analysis showed clear differences in microbiome composition between groups. Acetate, product of fibre fermentation, was higher in the Chow (p<0.0001) and IN (p=0.0195) groups whereas branched-chain fatty acids (BCFA), product of protein fermentation, was higher in the FF-free group (p<0.0001) Conclusions Spontaneous colitis development in FF-free fed Muc2-/- mice was observed within 10 days (5–6 weeks old) of weaning whereas Chow or IN fed mice showed minimal to no signs of colitis, respectively. A diet devoid of fibre also led to less mucin staining and a gut microbiome shift that favoured BCFA over SCFA production, suggesting the microbiota of FF-free fed Muc2-/- mice are targeting mucosal proteins concurrent with disease exacerbation. These findings support future studies examining whether consumption of low fibre diets in UC patients worsen disease outcomes whereas diets rich in fibre and/or inulin prove beneficial Funding Agencies CCC, CIHRMSFHR Trainee Award, CH.I.L.D foundation

In Vitro Assessment of Hydrolysed Collagen Fermentation Using Domestic Cat (Felis catus) Faecal Inocula.

Simple SummaryThe gastrointestinal microbiome of domestic cats can utilise dietary fibre to produce beneficial fermentation end products such as butyrate, an energy source for intestinal cells. However, domestic cats are obligate carnivores and therefore may not require plant derived dietary fibre. It has been hypothesised that in the wild, consumption of animal-derived substrates such as hair and cartilage may be fermented by the cat’s gastrointestinal microbiome, producing butyrate and other beneficial end products. Therefore, the aim of this study was to use a laboratory digestion and fermentation model (simulating the digestion process) to determine the concentrations of butyrate produced by various animal-derived substrates, including hydrolysed collagen, hair, and cartilage. Faecal samples were used in batch cultures to represent the microbes in the cat’s colon. Faecal samples came from cats fed either high protein or high carbohydrate diets. The type of faeces used was found to affect the fermentation profile produced, likely due to differing microbial community compositions, at the start of the batch cultures. Microbes present in high protein faeces fermented the hydrolysed collagen substrate, producing increased concentrations of butyrate. This finding has wider implications for use of animal-derived substrates in species-appropriate diet formulations.The gastrointestinal microbiome has a range of roles in the host, including the production of beneficial fermentation end products such as butyrate, which are typically associated with fermentation of plant fibres. However, domestic cats are obligate carnivores and do not require carbohydrates. It has been hypothesised that in the wild, collagenous parts of prey—the so-called animal-derived fermentable substrates (ADFS) such as tendons and cartilage—may be fermented by the cat’s gastrointestinal microbiome. However, little research has been conducted on ADFS in the domestic cat. Faecal inoculum was obtained from domestic cats either consuming a high carbohydrate (protein:fat:carbohydrate ratio of 35:20:28 (% dry matter basis)) or high protein (protein:fat:carbohydrate ratio of 75:19:1 (% dry matter basis)) diet. ADFS (hydrolysed collagen, cat hair, and cartilage) were used in a series of static in vitro digestions and fermentations. Concentrations of organic acids and ammonia were measured after 24 h of fermentation, and the culture community of microbes was characterised. The type of inoculum used affected the fermentation profile produced by the ADFS. Butyrate concentrations were highest when hydrolysed collagen was fermented with high protein inoculum (p < 0.05). In contrast, butyrate was not detectable when hydrolysed collagen was fermented in high carbohydrate inoculum (p < 0.05). The microbiome of the domestic cat may be able to ferment ADFS to provide beneficial concentrations of butyrate.

Butyric Acid Precursor Tributyrin Modulates Hippocampal Synaptic Plasticity and Prevents Spatial Memory Deficits: Role of PPARγ and AMPK.

BackgroundShort chain fatty acids (SCFA), such as butyric acid (BA), derived from the intestinal fermentation of dietary fiber and contained in dairy products, are gaining interest in relation to their possible beneficial effects on neuropsychological disordersMethodsC57BL/6J male mice were used to investigate the effect of tributyrin (TB), a prodrug of BA, on hippocampus (HIP)-dependent spatial memory, HIP synaptic transmission and plasticity mechanisms, and the expression of genes and proteins relevant to HIP glutamatergic transmission.ResultsEx vivo studies, carried out in HIP slices, revealed that TB can transform early-LTP into late-LTP (l-LTP) and to rescue LTP-inhibition induced by scopolamine. The facilitation of l-LTP induced by TB was blocked both by GW9662 (a PPARγ antagonist) and C-Compound (an AMPK inhibitor), suggesting the involvement of both PPARγ and AMPK on TB effects. Moreover, 48-hour intake of a diet containing 1% TB prevented, in adolescent but not in adult mice, scopolamine-induced impairment of HIP-dependent spatial memory. In the adolescent HIP, TB upregulated gene expression levels of Pparg, leptin, and adiponectin receptors, and that of the glutamate receptor subunits AMPA-2, NMDA-1, NMDA-2A, and NMDA-2B.ConclusionsOur study shows that TB has a positive influence on LTP and HIP-dependent spatial memory, which suggests that BA may have beneficial effects on memory.

POS-448 ACETATE ATTENUATES RENAL FIBROSIS IN AN OXIDATIVE STRESS MANNER

Short-chain fatty acids (SCFAs) are end products from the fermentation of dietary fibers by the intestinal microbiota. SCFAs have been shown to positive effects on host physiology. The most abundant SCFA is acetate. The protective roles of SCFAs including acetate have been expected due to energy source, due to histone acetylation, by working as histone deacetylase (HDAC) inhibitors, and by binding G-protein membrane receptors (GPR41 and GPR43). Regarding kidney disease, it was reported that SCFAs improved AKI in IRI mice model.

Gut microbiota-derived short-chain fatty acids and colorectal cancer: Ready for clinical translation?

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death worldwide. It involves the complex interactions between genetic factors, environmental exposure, and gut microbiota. Specific changes in the gut microbiome and metabolome have been described in CRC, supporting the critical role of gut microbiota dysbiosis and microbiota-related metabolites in the tumorigenesis process. Short-chain fatty acids (SCFAs), the principal metabolites generated from the gut microbial fermentation of insoluble dietary fiber, can directly activate G-protein-coupled receptors (GPCRs), inhibit histone deacetylases (HDACs), and serve as energy substrates to connect dietary patterns and gut microbiota, thereby improving the intestinal health. A significantly lower abundance of SCFAs and SCFA-producing bacteria has been demonstrated in CRC, and the supplementation of SCFA-producing probiotics can inhibit intestinal tumor development. SCFAs-guided modulation in both mouse and human CRC models augmented their responses to chemotherapy and immunotherapy. This review briefly summarizes the complex crosstalk between SCFAs and CRC, which might inspire new approaches for the diagnosis, treatment and prevention of CRC on the basis of gut microbiota-derived metabolites SCFAs.

Fecal and soil microbiota composition of gardening and non-gardening families

Historically, humans have interacted with soils, which contain a rich source of microorganisms. Fruit and vegetable gardening is the primary interaction humans have with soil today. Animal research reveals that soil microorganisms can be transferred to the rodent intestine. However, studies on fecal and soil microbial changes associated with gardening in humans are lacking. The current case-controlled cohort study aimed to characterize the fecal and soil microbiota of gardening families (n = 10) and non-gardening (control) families (n = 9). Families included two adults and one child (5–18 years) for a total of 56 participants. All participants provided a fecal sample, soil sample, and diet history questionnaires before the gardening season (April) and during the peak of the gardening season (August). Healthy Eating Index (HEI-2015) scores and nutrient analysis were performed. Fecal and soil DNA were extracted and amplified. Sequence data were then processed and analyzed. Peak season gardening families tended to have greater fecal operational features, a greater Faith's Phylogenetic Diversity score, greater fiber intake, and higher abundances of fiber fermenting bacteria than peak control families. Soil endemic microbes were also shared with gardening participant’s fecal samples. This study revealed that the fecal microbiota of gardening families differs from non-gardening families, and that there are detectable changes in the fecal microbial community of gardeners and their family members over the course of the gardening season. Additional research is necessary to determine if changes induced by gardening on the gut microbiota contribute to human health.

P705 The effects of commonly consumed dietary fibres on the gut microbiome and its fibre fermentative capacity in adults with inflammatory bowel disease in remission

Abstract Background It has been suggested that the gut microbiome of patients with inflammatory bowel disease (IBD) is unable to ferment dietary fibre. This project explored the in vitro effect of fibre fermentation on production of short chain fatty acids (SCFA) and on microbiome composition. Methods Faecal samples were collected from 40 adults (&amp;gt;16 y) with IBD (n=20 with Crohn’s disease and n=20 with Ulcerative colitis) in clinical remission and 20 healthy controls (HC). In vitro batch culture fermentations were carried out using as substrates maize starch, apple pectin, raftilose, wheat bran, α cellulose and a mixture of these 5 fibres. SCFA concentration (umol/g) was quantified with gas chromatography and microbiome was profiled with 16S rRNA sequencing. Results Fibre fermentation did not correct the baseline microbial dysbiosis or lower diversity seen in either CD or UC. For all fibres, up to 51% of baseline ASVs or genera changed in abundance in HC. In patients with IBD, fermentation of fibre substrates had no effect on species or genera abundance. Production of SCFA varied among the different fibre substrates but this was not different between the two IBD groups and compared to HC after either 5 or 24 hour fermentation. Conclusion Despite extensive microbial dysbiosis, patients with IBD have a similar capacity to ferment fibre and release SCFA as HC. Fibre supplementation alone may be unlikely to restore to a healthy status the compositional shifts characteristic of the IBD microbiome.

Gut Microbiota and Short Chain Fatty Acids: Implications in Glucose Homeostasis.

Gut microbiota encompasses a wide variety of commensal microorganisms consisting of trillions of bacteria, fungi, and viruses. This microbial population coexists in symbiosis with the host, and related metabolites have profound effects on human health. In this respect, gut microbiota plays a pivotal role in the regulation of metabolic, endocrine, and immune functions. Bacterial metabolites include the short chain fatty acids (SCFAs) acetate (C2), propionate (C3), and butyrate (C4), which are the most abundant SCFAs in the human body and the most abundant anions in the colon. SCFAs are made from fermentation of dietary fiber and resistant starch in the gut. They modulate several metabolic pathways and are involved in obesity, insulin resistance, and type 2 diabetes. Thus, diet might influence gut microbiota composition and activity, SCFAs production, and metabolic effects. In this narrative review, we discuss the relevant research focusing on the relationship between gut microbiota, SCFAs, and glucose metabolism.

Investigation of fiber utilization in the rumen of dairy cows based on metagenome-assembled genomes and single-cell RNA sequencing

BackgroundDairy cows utilize human-inedible, low-value plant biomass to produce milk, a low-cost product with rich nutrients and high proteins. This process largely relies on rumen microbes that ferment lignocellulose and cellulose to produce volatile fatty acids (VFAs). The VFAs are absorbed and partly metabolized by the stratified squamous rumen epithelium, which is mediated by diverse cell types. Here, we applied a metagenomic binning approach to explore the individual microbes involved in fiber digestion and performed single-cell RNA sequencing on rumen epithelial cells to investigate the cell subtypes contributing to VFA absorption and metabolism.ResultsThe 52 mid-lactating dairy cows in our study (parity = 2.62 ± 0.91) had milk yield of 33.10 ± 6.72 kg. We determined the fiber digestion and fermentation capacities of 186 bacterial genomes using metagenomic binning and identified specific bacterial genomes with strong cellulose/xylan/pectin degradation capabilities that were highly associated with the biosynthesis of VFAs. Furthermore, we constructed a rumen epithelial single-cell map consisting of 18 rumen epithelial cell subtypes based on the transcriptome of 20,728 individual epithelial cells. A systematic survey of the expression profiles of genes encoding candidates for VFA transporters revealed that IGFBP5+ cg-like spinous cells uniquely highly expressed SLC16A1 and SLC4A9, suggesting that this cell type may play important roles in VFA absorption. Potential cross-talk between the microbiome and host cells and their roles in modulating the expression of key genes in the key rumen epithelial cell subtypes were also identified.ConclusionsWe discovered the key individual microbial genomes and epithelial cell subtypes involved in fiber digestion, VFA uptake and metabolism, respectively, in the rumen. The integration of these data enables us to link microbial genomes and epithelial single cells to the trophic system.1dVKuikNrJ1xsEB1JvqD2DVideo abstract

Does a high dietary intake of resistant starch affect glycaemic control and alter the gut microbiome in women with gestational diabetes? A randomised control trial protocol

BackgroundGestational Diabetes Mellitus (GDM) is prevalent with lasting health implications for the mother and offspring. Medical nutrition therapy is the foundation of GDM management yet achieving optimal glycaemic control often requires treatment with medications, like insulin. New dietary strategies to improve GDM management and outcomes are required.Gut dysbiosis is a feature of GDM pregnancies, therefore, dietary manipulation of the gut microbiota may offer a new avenue for management. Resistant starch is a fermentable dietary fibre known to alter the gut microbiota and enhance production of short-chain fatty acids. Evidence suggests that short-chain fatty acids improve glycaemia via multiple mechanisms, however, this has not been evaluated in GDM.MethodsAn open-label, parallel-group design study will investigate whether a high dietary resistant starch intake or resistant starch supplement improves glycaemic control and changes the gut microbiome compared with standard dietary advice in women with newly diagnosed GDM. Ninety women will be randomised to one of three groups - standard dietary treatment for GDM (Control), a high resistant starch diet or a high resistant starch diet plus a 16 g resistant starch supplement. Measurements taken at Baseline (24 to 30-weeks’ gestation), Day 10 and Day 56 (approximately 36 weeks’ gestation) will include fasting plasma glucose levels, microbial composition and short-chain fatty acid concentrations in stool, 3-day dietary intake records and bowel symptoms questionnaires. One-week post-natal data collection will include microbial composition and short-chain fatty acid concentrations of maternal and neonatal stools, microbial composition of breastmilk, birthweight, maternal and neonatal outcomes. Mixed model analysis of variance will assess change in glycaemia and permutation-based multivariate analysis of variance will assess changes in microbial composition within and between intervention groups. Distance-based linear modelling will identify correlation between change in stool microbiota, short-chain fatty acids and measures of glycaemia.DiscussionTo improve outcomes for GDM dyads, evaluation of a high dietary intake of resistant starch to improve glycaemia through the gut microbiome needs to be established. This will expand the dietary interventions available to manage GDM without medication.Trial registrationAustralian New Zealand Clinical Trial Registry, ACTRN12620000968976p. Registered 28 September 2020

Short-Chain Fatty Acid Butyrate Induces Cilia Formation and Potentiates the Effects of HDAC6 Inhibitors in Cholangiocarcinoma Cells.

Cholangiocarcinoma (CCA) is a deadly form of liver cancer with limited therapeutic approaches. The pathogenesis of CCA involves the loss of primary cilia in cholangiocytes, an important organelle that regulates several key cellular functions including the regulation of cell polarity, growth, and differentiation, by a mechanism involving increased expression of deacetylases like HDAC6 and SIRT1. Therefore, cilia restoration may represent an alternative and novel therapeutic approach against CCA. Butyrate is produced by bacterial fermentation of fibers in the intestine and has been shown to inhibit SIRT1, showing antitumor effects on various cancers. Herein, we investigated the role of butyrate on CCA cell proliferation, migration, and EMT and evaluated the synergistic effects with specific HDAC6 inhibition. When CCA cells, including HuCCT1 and KMCH, were treated with butyrate, the cilia formation and acetylated-tubulin levels were increased, while no significant effects were observed in normal human cholangiocytes. Butyrate treatment also depicted reduced cell proliferation in HuCCT1 and KMCH cells, but on the other hand, it affected cell growth of the normal cholangiocytes only at high concentrations. In HuCCT1 cells, spheroid formation and cell migration were also halted by butyrate treatment. Furthermore, we found that butyrate augmented the previously described effects of HDAC6 inhibitors on CCA cell proliferation and migration by reducing the expression of CD44, cyclin D1, PCNA, Zeb1, and Vimentin. In summary, butyrate targets cancer cell growth and migration and enhances the anti-cancer effects of HDAC6 inhibitors in CCA cells, suggesting that butyrate may have therapeutic effects in CCA and other ciliopathies.

Colonic expression of calcium transporter TRPV6 is regulated by dietary sodium butyrate.

Dietary fibers have been shown to increase the intestinal absorption of calcium (Ca2+) and magnesium (Mg2+). However, the mechanisms that explain the enhanced electrolyte absorption remain unknown. Therefore, this study aims to investigate the short-term and long-term effects of 5% (w/w) sodium butyrate (Na-butyrate), an important end-metabolite of bacterial fermentation of dietary fibers, on Ca2+ and Mg2+ homeostasis in mice. Serum Ca2+ levels were only significantly increased in mice treated with Na-butyrate for 1day. This was associated with a twofold increase in the mRNA expression levels of Trpv6 in the proximal and distal colon. Contrary, Na-butyrate did not affect serum Mg2+ concentrations at either of the intervention periods. However, we observed a reduction in urinary Mg2+ excretion, although not significantly, after 1day of treatment. A significant reduction of 2.5-fold in urinary Mg2+ excretion was observed after 14days of treatment. Indeed, 14-day Na-butyrate supplementation increased colonic Trpm7 expression by 1.2-fold compared to control mice. In conclusion, short-term Na-butyrate supplementation increases serum Ca2+ levels in mice. This was associated with increased mRNA expression levels of Trpv6 in the colon, suggesting that Na-butyrate regulates the expression of genes involved in active intestinal Ca2+ absorption.

Inulin Supplementation Mitigates Gut Dysbiosis and Brain Impairment Induced by Mild Traumatic Brain Injury during Chronic Phase.

Mild traumatic brain injury (mTBI) has been shown to acutely alter the gut microbiome diversity and composition, known as dysbiosis, which can further exacerbate metabolic and vascular changes in the brain in both humans and rodents. However, it remains unknown how mTBI affects the gut microbiome in the chronic phase recovery (past one week post injury). It is also unknown if injury recovery can be improved by mitigating dysbiosis. The goal of the study is to fill the knowledge gap. First, we aim to understand how mTBI alters the gut microbiome through the chronic period of recovery (3 months post injury). In addition, as the gut microbiome can be modulated by diet, we also investigated if prebiotic inulin, a fermentable fiber that promotes growth of beneficial bacteria and metabolites, would mitigate dysbiosis, improve systemic metabolism, and protect brain structural and vascular integrity when administered after 3 months post closed head injury (CHI). We found that CHI given to male mice at 4 months of age induced gut dysbiosis which peaked at 1.5 months post injury, reduced cerebral blood flow (CBF) and altered brain white matter integrity. Interestingly, we also found that Sham mice had transient dysbiosis, which peaked 24 hours after injury and then normalized. After 8 weeks of inulin feeding, CHI mice had increased abundance of beneficial/anti-inflammatory bacteria, reduced abundance of pathogenic bacteria, enriched levels of short-chain fatty acids, and restored CBF in both hippocampi and left thalamus, compared to the CHI-control fed and Sham groups. Using machine learning, we further identified top bacterial species that separate Sham and CHI mice with and without the diet. Our results indicate that there is an injury- and time-dependent dysbiosis between CHI and Sham mice; inulin is effective to mitigate dysbiosis and improve brain injury recovery in the CHI mice. As there are currently no effective treatments for mTBI, the study may have profound implications for developing therapeutics or preventive interventions in the future.

Commensal microbe-derived SCFA alleviates atrial fibrillation via GPR43/NLRP3 signaling.

Rationale: Dysbiotic gut microbiota (GM) and NLRP3 inflammasome are proarrhythmic factors in atrial fibrillation (AF). Herein, whether short-chain fatty acid (SCFA) produced from GM fermentation of dietary fiber serving as invisible mediators is yet unclear. Thus, the current study aimed to determine whether SCFA alleviated from NLRP3 signaling-mediated atrial remodeling protects AF development.Methods: First, a cross-sectional study based on the GC-MS metabolomics was performed to explore the association between fecal SCFA levels and AF traits in a cohort consisted of 48 individuals. Then, a well-established mice model fed diet deficient or enriched in dietary fiber was established to elucidate the pathophysiological role of SCFA involved in AF susceptibility, atrial remodeling, and G-protein-coupled receptor 43 (GPR43)/NLRP3 signaling. Finally, the effects of SCFA were verified on HL-1 cells.Results: Fecal SCFA levels were remarkably reduced in AF patients with a declining trend from paroxysmal to persistent AF. Prolonged P wave duration based on surface ECG and increased left atrial diameter gained from echocardiography was identified in low-fiber diet mice but lost in SCFA-supplemented group. Lack of dietary fiber enhanced susceptibility to AF under burst pacing, whereas SCFA might exert a protective effect. The supplementation of SCFA prevented dietary fiber deficiency-upregulated phosphorylation of calmodulin-dependent protein kinase II and ryanodine receptor 2, the disarray fibrosis, collagen expression, and NLRP3 inflammasome activation in atrial tissue. Finally, the AF protective roles of SCFA were identified through GPR43 mediated deactivation of NLRP3 by GPR43 knockdown in HL-1 cells.Conclusions: SCFA derived from dietary fiber fermentation by gut commensals alleviates AF development via GPR43/NLRP3 signaling.

Mechanisms of Short-Chain Fatty Acids Derived from Gut Microbiota in Alzheimer's Disease.

Short-chain fatty acids (SCFAs) are important metabolites derived from the gut microbiota through fermentation of dietary fiber. SCFAs participate a number of physiological and pathological processes in the human body, such as host metabolism, immune regulation, appetite regulation. Recent studies on gut-brain interaction have shown that SCFAs are important mediators of gut-brain interactions and are involved in the occurrence and development of many neurodegenerative diseases, including Alzheimer's disease. This review summarizes the current research on the potential roles and mechanisms of SCFAs in AD. First, we introduce the metabolic distribution, specific receptors and signaling pathways of SCFAs in human body. The concentration levels of SCFAs in AD patient/animal models are then summarized. In addition, we illustrate the effects and mechanisms of SCFAs on the cognitive level, pathological features (Aβ and tau) and neuroinflammation in AD. Finally, we analyze the translational value of SCFAs as potential therapeutic targets for the treatment of AD.

Research Progress in Regulation of Allergic Diseases by Short-Chain Fatty Acids

Gut microbiota-derived metabolites play vital roles in the regulation of host-gut microbiota mutualism, gut homeostasis and the pathogenesis of multiple human diseases. Fermentation of indigestible dietary fibers by gut microbiota produces a variety of short-chain fatty acids (SCFAs) consisting mainly of acetate, propionate and butyrate. Despite high concentrations of SCFAs in the gut, it has been reported in a large number of studies that SCFAs are involved in the onset and development of multiple diseases, including colitis, diabetes mellitus, hepatic steatosis, and obesity. Recent studies including our work found that SCFAs regulates allergic immune reactions and the pathogenesis of allergic diseases via their action on allergic effector immune cells, including T helper 2 (Th2) cells, type 2 innate lymphoid cells (ILC2), eosinophils, mast cells and basophils. Herein, we reviewed the association of SCFAs with human allergic diseases, their role in regulating the animal model of allergic diseases and the effects of different SCFAs in regulating the functions of allergic effectors cells and the underlying mechanisms, aiming to provide research clues for in-depth investigation in the role played by SCFAs in regulating various allergic diseases.

Production of high-quality silage from invasive plants plus agro-industrial by-products with or without bacterial inoculation

The aim of the current study was to formulate novel blends from two invasive plants ( Hedychium gardnerianum ; HG and Pittosporum undulatum ; PU) with or without agro-industrial by-products (chemical additives; CA) and lactic acid bacteria (LAB) to produce high-quality silage. PU was incorporated with HG at two levels 20% or 40% (w/w). Ensiling experiments were conducted for 60 days at room temperature. Chemical composition, microbial populations and in vitro digestibility of forages were determined before and after ensiling. The fermentation products and aerobic stability of feeds were only measured post-ensiling. The results revealed that all the produced silages were successfully conserved. Using of LAB inoculants produced silages less stable in air. Treatments consisting of PU (40%), CA and LAB resulted in high-quality and highly nutritive silages according to the feed quality parameters (fermentation end products, crude protein, fiber fractions and digestibility). Therefore, these silages are proposed as an alternative feed for ruminants. • Azores are rich with Hedychium gardnerianum (HG) and Pittosporum undulatum (PU). • The combination of two levels of PU with HG led to better fermentation features. • Silages received PU (40%), chemical additives and inoculants were highly nutritive. • The used inoculants revealed similar results, except for fiber degradation. • Bacterial inoculation impaired the aerobic stability of silages.

Evaluating tolerability of resistant starch 2, alone and in combination with minimally fermented fibre for patients with irritable bowel syndrome: a pilot randomised controlled cross-over trial.

Resistant starch 2 (RS2) may offer therapeutic value to irritable bowel syndrome (IBS) patients particularly in combination with minimally fermented fibre, but tolerability data are lacking. The present study evaluated the tolerability of RS2, sugarcane bagasse and their combination in IBS patients and healthy controls. Following baseline, participants consumed the fibres in escalating doses lasting 3 d each: RS2 (10, 15 and 20 g/d); sugarcane bagasse (5, 10 and 15 g/d); and their combination (20, 25 and 30 g/d). Gastrointestinal symptoms were assessed daily. Six IBS patients and five controls were recruited. No differences in overall symptoms from baseline were found across the fibre doses (IBS, P = 0⋅586; controls, P = 0⋅687). For IBS patients, all RS2 doses led to increased bloating. One IBS patient did not tolerate the low combination dose and another the high sugarcane bagasse dose. Supplementation of RS2 ≤ 20 g/d caused mild symptoms and was generally tolerated in IBS patients even when combined with minimally fermented fibre.

Fiber mixture-specific effect on distal colonic fermentation and metabolic health in lean but not in prediabetic men

ABSTRACT Infusions of the short-chain fatty acid (SCFA) acetate in the distal colon improved metabolic parameters in men. Here, we hypothesized that combining rapidly and slowly fermentable fibers will enhance distal colonic acetate production and improve metabolic health. In vitro cultivation studies in a validated model of the colon were used to identify fiber mixtures that yielded high distal colonic acetate production. Subsequently, in two randomized crossover studies, lean and prediabetic overweight/obese men were included. In one study, participants received supplements of either long-chain inulin+resistant starch (INU+RS), INU or maltodextrin (PLA) the day prior to a clinical investigation day (CID). The second trial studied beta glucan+RS (BG+RS) versus BG and PLA. During each CID, breath hydrogen, indirect calorimetry, plasma metabolites/hormones were assessed during fasting and postprandial conditions. Additionally, fecal microbiota composition and SCFA were determined. In prediabetic men, INU+RS increased plasma acetate compared to INU or PLA (P < .05), but did not affect metabolic parameters. In lean men, INU+RS increased breath hydrogen and fasting plasma butyrate, which was accompanied by increased energy expenditure, carbohydrate oxidation and PYY and decreased postprandial glucose concentrations (all P < .05) compared to PLA. BG+RS increased plasma butyrate compared to PLA (P < .05) in prediabetic individuals, but did not affect other fermentation/metabolic markers in both phenotypes. Fiber-induced shifts in fecal microbiota were individual-specific and more pronounced with INU+RS versus BG+RS. Administration of INU+RS (not BG+RS) the day prior to investigation improved metabolic parameters in lean but not in prediabetic individuals, demonstrating that effects were phenotype- and fiber-specific. Further research should study whether longer-term supplementation periods are required to elicit beneficial metabolic health in prediabetic individuals. Trial registration numbers: Clinical trial No. NCT03711383 (Inulin study) and Clinical trial No. NCT03714646 (Beta glucan study).