Fermentable Fiber Research Articles

Optimization of laccase production by Pleurotus pulmonarius through solid substrate fermentation of tender coconut fiber: enhanced laccase production and biomass delignification

Optimization of laccase production by Pleurotus pulmonarius through solid substrate fermentation of tender coconut fiber: enhanced laccase production and biomass delignification

Propionate Decreases Microglial Activation but Impairs Phagocytic Capacity in Response to Aggregated Fibrillar Amyloid Beta Protein.

Microglia, the innate immune cell of the brain, are a principal player in Alzheimer's disease (AD) pathogenesis. Their surveillance of the brain leads to interaction with the protein aggregates that drive AD pathogenesis, most notably Amyloid Beta (Aβ). Microglia attempt to clear and degrade Aβ using phagocytic machinery, spurring damaging neuroinflammation in the process. Thus, modulation of the microglial response to Aβ is crucial in mitigating AD pathophysiology. SCFAs, microbial byproducts of dietary fiber fermentation, are blood-brain barrier permeable molecules that have recently been shown to modulate microglial function. It is unclear whether propionate, one representative SCFA, has beneficial or detrimental effects on microglia in AD. Thus, we investigated its impact on microglial Aβ response in vitro. Using a multiomics approach, we characterized the transcriptomic, metabolomic, and lipidomic responses of immortalized murine microglia following 1 h of Aβ stimulation, as well as characterizing Aβ phagocytosis and secretion of reactive nitrogen species. Propionate blunted the early inflammatory response driven by Aβ, downregulating the expression of many Aβ-stimulated immune genes, including those regulating inflammation, the immune complement system, and chemotaxis. Further, it reduced the expression of Apoe and inflammation-promoting Aβ-binding scavenger receptors such as Cd36 and Msr1 in favor of inflammation-dampening Lpl, although this led to impaired phagocytosis. Finally, propionate shifted microglial metabolism, altering phospholipid composition and diverting arginine metabolism, resulting in decreased nitric oxide production. Altogether, our data demonstrate a modulatory role of propionate on microglia that may dampen immune activation in response to Aβ, although at the expense of phagocytic capacity.

Microbiota-derived short chain fatty acids in pediatric health and diseases: from gut development to neuroprotection.

The infant gut microbiota undergoes significant changes during early life, which are essential for immune system maturation, nutrient absorption, and metabolic programming. Among the various microbial metabolites, short-chain fatty acids (SCFAs), primarily acetate, propionate, and butyrate, produced through the fermentation of dietary fibers by gut bacteria, have emerged as critical modulators of host-microbiota interactions. SCFAs serve as energy sources for colonic cells and play pivotal roles in regulating immune responses, maintaining gut barrier integrity, and influencing systemic metabolic pathways. Recent research highlights the potential neuroprotective effects of SCFAs in pediatric populations. Disruptions in gut microbiota composition and SCFA production are increasingly associated with a range of pediatric health issues, including obesity, allergic disorders, inflammatory bowel disease (IBD), and neurodevelopmental disorders. This review synthesizes current knowledge on the role of microbiota-derived SCFAs in pediatric health, emphasizing their contributions from gut development to neuroprotection. It also underscores the need for further research to unravel the precise mechanisms by which SCFAs influence pediatric health and to develop targeted interventions that leverage SCFAs for therapeutic benefits.

B-172 Correlation of Microbiome Sequencing Data and Quantified Short-Chain Fatty Acids by LC-MS/MS in IBD and Non-IBD Stool Samples

Abstract Background SCFAs are the primary metabolites produced by bacterial fermentation of dietary fiber and undigested proteins. They play a crucial role in various metabolic pathways, such as regulating the host’s energy balance and anti-inflammatory processes. The most studied SCFAs are acetic acid, propionic acid and butyric acid, with an approximate molecular ratio of 60:20:20 in healthy adults. A significantly different distribution may indicate a bacterial dysbiosis. While most SCFAs have a positive impact on the host’s health, the impact of branched short-chain fatty acids (bSCFAs), such as isobutyric acid and isovaleric acid, are less well-known. In order to evaluate whether the determination of a broader SCFA panel holds additional diagnostic value, we have developed a sensitive and robust LC-MS/MS method to determine 11 C2 - C7 SCFAs in human fecal samples. Methods The LC-MS/MS method includes acetic acid (AA), propionic acid (PA), butyric acid (BA), valeric acid (VA), caproic acid (CA) and heptanoic acid (HA), as well as the isomers isobutyric acid (iBA), 2-methylbutyric acid (2-MBA), isovaleric acid (iVA), isocaproic acid (iCA) and 2-methylhexanoic acid (2-MHA). After suspending the stool samples in a stabilizing buffer, the tubes were centrifuged and 25 µl of the supernatant was mixed with an internal standard solution (10 isotopically labeled internal standards) and subsequently derivatized. After one hour, the reaction was quenched and samples were injected into an ACQUITY UPLC H-Class (Waters) with an injection cycle of 9.5 min. Analytes were measured in positive mode by ESI-MS/MS on a Xevo TQ-MS (Waters). For quantification, six calibrators and three controls covering the anticipated physiological ranges were used. Results Microbiome sequencing data identified a total of 193 species, most of which belong to the Firmicutes phylum. Next, Actinobacteria and Proteobacteria are in descending order of abundance. In our IBD samples, we see a significant dysbiosis of these ratios and orders in comparison to the screening patients. E.g. in one sample, no Bacteroidetes were found, but a high amount of Actinobacteria (40 %) were sequenced. Corresponding SCFA data detected an AA:PA:BA ratio of 76:11:10, as well as no VA, iCA, CA, 2-MHA and HA, whereas SCFA data from most screening patients showed an AA:PA:BA ratio of 60:20:20 (± 10:10:10). Conclusions After a fast and simple sample preparation and derivatization, the LC MS/MS method allows robust and sensitive measurement of all presented SCFAs from human feces samples. The preliminary analysis of the combined microbiome and SCFA data showed that the detected AA:PA:BA ratio difference could be a valid indicator for a dysbiosis or an altered microbiome, corroborating data from previous studies. While we could detect differences on bSCFAs and longer SCFAs between IBD and non-IBD patient samples in this pilot study, larger patient and control cohorts are needed in order to substantiate our initial promising findings and finally allow a robust evaluation of these parameters as diagnostic tool to monitor and determine the state of the patient microbiome.

Dietary fibre and metabolic health: A clinical primer.

Dietary fibres consist of a heterogeneous group of carbohydrate polymers which resist digestion by human gastrointestinal enzymes. Consumption of dietary fibre has been linked with innumerable health benefits encompassing the foundational pillars of metabolic health from obesity to hypertension, dyslipidaemia, and type 2 diabetes mellitus (T2DM), with many of these benefits linked with metabolites produced by the fermentation of fibre by gut microbes [1]. The potential of dietary fibre to provide a safe and effective nonpharmacologic complementary tool with which to combat the evolving consequences of the obesity epidemic has recently garnered tremendous attention in both medical literature and lay media alike. HIGHLIGHTS: Consumption of dietary fibre has been linked with innumerable health benefits encompassing the foundational pillars of metabolic health with many of these benefits linked with metabolites produced by the fermentation of fibre by gut microbes At the present time clinicians are faced with an impossible task in which there is rapidly mounting evidence for dietary fibres advancing metabolic health, but little practical options for healthcare providers other than to simply recommend patients consume more fibre. Benefits of fibre intake may perhaps be maximised in an individual by matching specific fibre consumption with existing microbial functional characteristics If dietary fibres could be demonstrated to act as successful adjuncts to sustain or improve standard of care therapies or even alleviate common gastrointestinal side effects associated with current treatments, they would be an invaluable tool in our metabolic health armamentarium. Neither Dr. Madsen or I have any financial conflicts of interest pertinent to the contents of this manuscript.

A core microbiome signature as an indicator of health

The gut microbiota is crucial for human health, functioning as a complex adaptive system akin to a vital organ. To identify core health-relevant gut microbes, we followed the systems biology tenet that stable relationships signify core components. By analyzing metagenomic datasets from a high-fiber dietary intervention in type 2 diabetes and 26 case-control studies across 15 diseases, we identified a set of stably correlated genome pairs within co-abundance networks perturbed by dietary interventions and diseases. These genomes formed a "two competing guilds" (TCGs) model, with one guild specialized in fiber fermentation and butyrate production and the other characterized by virulence and antibiotic resistance. Our random forest models successfully distinguished cases from controls across multiple diseases and predicted immunotherapy outcomes through the use of these genomes. Our guild-based approach, which is genome specific, database independent, and interaction focused, identifies a core microbiome signature that serves as a holistic health indicator and a potential common target for health enhancement.

Impact of Fermentable and Viscous Dietary Fiber on Gut-Derived Uremic Toxins in Rats with Progressive CKD

Impact of Fermentable and Viscous Dietary Fiber on Gut-Derived Uremic Toxins in Rats with Progressive CKD

Effects Of Fermentable Fiber And Polyphenol Supplementation On Mood And Cognition During Hypobaric Hypoxia Exposure

Effects Of Fermentable Fiber And Polyphenol Supplementation On Mood And Cognition During Hypobaric Hypoxia Exposure

A review of gut microbial metabolites and therapeutic approaches in hypertension

Abstract Background Hypertension is a prevalent and complex disease that is increasingly recognized to be influenced by the gut microbiome and its metabolites. Understanding the relationship between gut microbial metabolites and blood pressure regulation could provide new therapeutic avenues. Main body This review examines the role of key microbial metabolites—short-chain fatty acids, trimethylamine N-oxide, tryptophan derivatives, polyamines, bile acids, and phenylacetylglutamine—in blood pressure regulation. Short-chain fatty acids, produced through dietary fiber fermentation, can lower blood pressure by modulating immune responses and reducing inflammation. Elevated trimethylamine N-oxide levels are associated with increased cardiovascular risk and hypertension, influencing cholesterol metabolism and promoting atherosclerosis. Tryptophan derivatives interact with vascular and renal functions to modulate blood pressure. Polyamines affect blood pressure regulation through their impact on nitric oxide synthesis and vascular tone. Bile acids influence blood pressure via gut microbiota modulation and activation of metabolic receptors. Phenylacetylglutamine has been linked to hypertension through its effects on platelet hyperactivity and thrombosis. Therapeutic approaches targeting these metabolites, including probiotics, prebiotics, fecal microbiota transplantation, dietary interventions, and polyphenols, have shown varying degrees of success. Probiotics and prebiotics promote the growth of beneficial gut bacteria and may lower blood pressure. Dietary interventions, such as the Mediterranean diet, positively affect blood pressure and cardiovascular health by modulating the gut microbiota. Polyphenols, known for their antioxidant properties, are associated with blood pressure reductions and improved vascular function. Fecal microbiota transplantation shows promise in restoring gut microbial balance and improving metabolic health, potentially influencing blood pressure regulation. Conclusion The review highlights the significant role of gut microbial metabolites in regulating blood pressure, offering new avenues for hypertension management. Key metabolites, including short-chain fatty acids, trimethylamine N-oxide, and bile acids, play critical roles in blood pressure modulation. Therapeutic strategies targeting these metabolites, such as probiotics, prebiotics, and dietary interventions, hold promise, though further research is needed to fully understand their mechanisms and optimize their use. Advancing microbiota-based interventions through large-scale studies and exploring personalized therapies will be essential for developing effective treatments in hypertension management.

Multi-View Integrative Approach For Imputing Short-Chain Fatty Acids and Identifying Key factors predicting Blood SCFA.

Short-chain fatty acids (SCFAs) are the main metabolites produced by bacterial fermentation of dietary fiber within gastrointestinal tract. SCFAs produced by gut microbiotas (GMs) are absorbed by host, reach bloodstream, and are distributed to different organs, thus influencing host physiology. However, due to the limited budget or the poor sensitivity of instruments, most studies on GMs have incomplete blood SCFA data, limiting our understanding of the metabolic processes within the host. To address this gap, we developed an innovative multi-task multi-view integrative approach (M2AE, Multi-task Multi-View Attentive Encoders), to impute blood SCFA levels using gut metagenomic sequencing (MGS) data, while taking into account the intricate interplay among the gut microbiome, dietary features, and host characteristics, as well as the nuanced nature of SCFA dynamics within the body. Here, each view represents a distinct type of data input (i.e., gut microbiome compositions, dietary features, or host characteristics). Our method jointly explores both view-specific representations and cross-view correlations for effective predictions of SCFAs. We applied M2AE to two in-house datasets, which both include MGS and blood SCFAs profiles, host characteristics, and dietary features from 964 subjects and 171 subjects, respectively. Results from both of two datasets demonstrated that M2AE outperforms traditional regression-based and neural-network based approaches in imputing blood SCFAs. Furthermore, a series of gut bacterial species (e.g., Bacteroides thetaiotaomicron and Clostridium asparagiforme), host characteristics (e.g., race, gender), as well as dietary features (e.g., intake of fruits, pickles) were shown to contribute greatly to imputation of blood SCFAs. These findings demonstrated that GMs, dietary features and host characteristics might contribute to the complex biological processes involved in blood SCFA productions. These might pave the way for a deeper and more nuanced comprehension of how these factors impact human health.

The Protective Potential of Butyrate against Colon Cancer Cell Migration and Invasion Is Critically Dependent on Cell Type.

Short-chain fatty acids such as butyrate are produced through the fermentation of dietary fiber by colonic bacteria. Preclinical studies indicate an anticancer potential of butyrate, but clinical evidence shows greater variability. The study hypothesizes the effectiveness of butyrate on reducing colon cancer cell migration and invasion may vary due to the cell-type. The study determines the efficacy of butyrate (0-4mM) to inhibit cancer cell migration, invasion, and related signaling proteins in three distinct human colorectal cancer (CRC) cell lines: HCT116, HT-29, and Caco-2.Butyrate exhibits a dose-dependent inhibitory effect on cancer cell migration and invasion. This inhibitory potential on oncogenic focal adhesion kinase (FAK) and sarcoma (Src) proteins is greater in HCT116 cells (1.1 and 0.8-fold) and HT-29 cells (0.9 and 0.4-fold) compared to Caco-2 cells, respectively. Conversely, E-cadherin protein, a classical epithelial cell marker and potential tumor suppressor, is 2.3-fold greater in HCT116 cells than in HT-29 cells and Caco-2 cells. Moreover, survival analysis from a public cancer database demonstrates that CRC patients with high E-cadherin expression have a 13% greater 5-year survival rate than those with low expression. Collectively, butyrate's anti-cancer efficacy on CRC cells varies depending on cell-type and is linked to the FAK/Src/E-cadherin pathway.

Prebiotic activity of enzymatically modified pea peel dietary fiber: An in vitro study

The study examined the prebiotic index of enzymatically modified insoluble dietary fiber from pea peel by using three probiotic bacterias; Lactobacillus rhamnosus ATCC 7469, Lactobacillus sakei ATCC 15521, Lactobacillus plantarum ATCC 8014 and one pathogenic bacteria; Escherichia coli ATCC 4157. A positive value for prebiotic potential was determined which was greater than inulin, unmodified dietary fiber, and standard glucose. The 30 h of cultivation, the cell density obtained from Lactobacillus rhamnosus ATCC 7469 culture conducted in MRS was 7.45 ± 0.08 log CFU/mL in glucose medium and 7.37 ± 0.07 log CFU/mL in dietary fiber medium. Growth kinetics analysis showed a positive effect for Lactobacillus spp. in DF medium. DF could boost cell biomass and relative growth rate of probiotic bacteria. Thus, the microbiome of the colon facilitates dietary fiber fermentation by bacteria shown in in vitro simulated gastrointestinal model.

The Link between Salivary Amylase Activity, Overweight, and Glucose Homeostasis.

Butyrate, a short-chain fatty acid (SCFA) produced by the fermentation of dietary fibers in the colon, plays a pivotal role in regulating metabolic health, particularly by enhancing insulin sensitivity. Given the rising incidence of metabolic disorders, understanding the factors that influence butyrate production is of significant interest. This study explores the link between salivary amylase activity and butyrate levels in overweight women of reproductive age. Participants were categorized into low (LSA) and high (HSA) salivary amylase activity groups and further divided into two subgroups: one followed a low-starch diet (LS), and the other underwent caloric restriction (CR). We assessed salivary amylase activity and measured serum butyrate concentrations to examine their associations. Our findings showed a significant, though weak, positive correlation (ρ = 0.0486, p < 0.05), suggesting a link between salivary amylase activity and butyrate levels. The statistical significance, despite the weak correlation, implies that this relationship is not random. Moreover, higher baseline butyrate levels were observed in women with elevated salivary amylase activity. Also, women with low salivary amylase activity on a low-starch diet experienced a more pronounced increase in butyrate levels compared to those on caloric restriction. These results suggest that salivary amylase activity and dietary intake interact to influence butyrate production, with potential implications for improving insulin sensitivity and metabolic health. The study underscores the potential of butyrate in enhancing insulin sensitivity and promoting overall metabolic well-being. Further research is necessary to clarify the mechanisms involved and to understand the long-term effects of butyrate on metabolic health across different populations.

48 Dietary functional fiber properties for improved health and disease outcomes in pigs

Abstract In swine production, using feed antibiotics as antimicrobial growth promotants has been reduced; thus, feed alternatives to manage gut health are required. Dietary fiber and similar carbohydrate structures such as resistant starch, oligosaccharides, and exopolysaccharides are nutritional tools that may enhance gut health in pigs. Dietary fiber may have a role to alleviate diarrheal diseases including in pigs post-weaning but can also reduce constipation in sows, but specific functionality depends on fiber properties. Antibiotics are hypothesized to influence gut health via modulation of intestinal microbial profiles; fermentation and intestinal inflammation are considered important mechanisms. Dietary fiber sources differ in a key functional property: fermentability. Rapid fermentation of fiber and oligosaccharides is associated with changes in microbial profiles and increased metabolite production. Recently, microbial composition was hypothesized to be less important and combined output of metabolites should be the focus. Fiber properties may also manipulate retention time and physico-chemical properties of the undigested residue; hence, non-fermentable fiber may prevent constipation in sows. The fiber-like structure resistant starch is not digested and acts as fermentable fiber but has unique properties, because it specifically increases intestinal abundance of bifidobacteria, which are associated with improved gut health. Using crop breeding, feed processing, and feed additives, the structure of fiber and starch can be altered thereby changing its degradation kinetics and affecting its prebiotic activity. Finally, fiber-like structures such as exopolysaccharides from Limosilactobacillus reuteri and unique oligosaccharides may serve as receptor analogues for pathogenic bacteria, e.g., enterotoxigenic Escherichia coli (ETEC). These receptor analogues block lectin domains of bacterial adhesins and thus prevent adherence of pathogens to the gut wall, thereby avoiding initiation of post-weaning diarrhea. In conclusion, dietary fiber and similar structures possess important functional properties that may also provide important solutions to maintain gut health in pigs.

401 Effect of protein and starch supplementation level on intake and digestibility by steers consuming low-quality forage: I. Bos taurus

Abstract A deficiency of ruminally available N (RAN) caused by a basal diet of low-quality forage depresses forage utilization. Supplemental protein improves forage utilization by increasing RAN, resulting in increased intake and potentially improving digestion. Addition of starch to a supplement can increase total digestible organic matter (OM) intake (TDOMI); however, too much starch decreases RAN and pH potentially decreasing forage utilization. Our objective was to determine the effect of starch supplementation on intake and digestion in Bos taurus indicus steers. Accordingly, five ruminally cannulated Brahman steers [body weight (BW) = 420 ± 55 kg) were used in a 4 × 4 Latin square to evaluate the effect of decreasing supplemental starch when consuming King Ranch Bluestem hay (3.5% CP, 73% NDF). Steers received four isonitrogenous (130 mg N/ kg BW) supplements providing increasing levels of starch (2% starch = 100% soybean meal; 20% starch = 26.3% corn, 73% soybean meal, 0.7% urea; 38% starch = 51.6% corn, 47% soybean meal, 1.4% urea; 56% starch = 78.6% corn, 19% soybean meal, 2.4% urea). Five 14-d periods were conducted, consisting of 9 d adaptation and 4 d to measure intake and digestion, and 1 d for ruminal fermentation. As designed, supplement OM intake (SOMI) increased linearly (P &amp;lt; 0.01) as starch level increased. Other measures of intake, including forage OM intake (FOMI), total OM intake (TOMI), and total neutral detergent fiber intake (TNDFI) decreased in a cubic manner in response to increasing starch (P ≤ 0.04). Forage OMI also responded with a cubic decrease (72.2, 68.9, and 69.5 g/kg BW0.75) when the protein supplement contained 2, 20, and 38% starch, respectively, but decreased to 61.2 g/kg BW0.75 when the 56% starch supplement was provided. Similarly, TOMI decreased 5.3% when starch inclusion increased from 38 to 56%. Total tract OM digestion and NDF digestion were not significantly affected (P ≥ 0.86) by starch level in the supplement; therefore, despite TOMI and TNDFI decreasing, there was no effect on total digestible OM intake and (TDOMI) and total digestible NDF intake (TDNDFI). In conclusion, providing supplemental starch over 38% decreased forage utilization. Decreases in FOMI with starch inclusion may be attributed to competition for RAN between fiber fermenting and starch fermenting bacteria.

The role of gut-derived short-chain fatty acids in Parkinson's disease.

The emerging function of short-chain fatty acids (SCFAs) in Parkinson's disease (PD) has been investigated in this article. SCFAs, which are generated via the fermentation of dietary fiber by gut microbiota, have been associated with dysfunction of the gut-brain axis and, neuroinflammation. These processes are integral to the development of PD. This article examines the potential therapeutic implications of SCFAs in the management of PD, encompassing their capacity to modulate gastrointestinal permeability, neuroinflammation, and neuronal survival, by conducting an extensive literature review. As a whole, this article emphasizes the potential therapeutic utility of SCFAs as targets for the management and treatment of PD.

505 Utilizing porcine hepatocyte cultures to test the effect of short chain fatty acids on androstenone metabolism

Abstract Boar taint is an off-putting odor found in the meat of entire male pigs due to the accumulation of androstenone and skatole in the fat. Development of boar taint is dependent on the balance between the rate of synthesis and metabolism of these compounds. Prior studies have shown that feed ingredients high in fermentable carbohydrates, including chicory root, sugar beet pulp, and Jerusalem artichoke decreased the synthesis of skatole in the hindgut and altered the metabolism in the liver, resulting in a skatole concentrations comparable with castrated males. However, the mechanism of how these dietary fermentable carbohydrates affect liver metabolism is not well understood. Metabolism of boar taint compounds takes place in a two-phase process, regulated by various enzymes and cytochrome families. Short-chain fatty acids (SCFAs) are produced from the microbial fermentation of fiber and have been shown to have regulatory effects on histone deacetylases and gene expression in humans, providing a potential mechanism in which feed high in dietary fiber reduces boar taint. The purpose of this study was to assess if SCFA directly affect the metabolism of androstenone in liver hepatocytes. Primary hepatocytes were isolated from the liver of 6 [(Yorkshire x Landrace) x Duroc] boars weighing around 90 kg. Cells were treated in triplicate with acetate, butyrate, propionate, and various combinations for 24 h to alter gene expression. Two sets of wells acted as a control, not being treated with SCFAs. The cells were then incubated with androstenone for 3 h, and media was extracted, and metabolite production was analyzed using high-performance liquid chromatography. The effects of treatments were using a one-way ANOVA with a Dunnet’s adjustment for multiple comparisons to a control. Results showed the combined acetate, butyrate, and propionate treatment had the greatest effect on androstenone glucuronide production when compared with the control, resulting in significant increases (P &amp;lt; 0.05) ranging from 82 ± 1.6% to 1 ± 2.4% in individual boars. Other treatments had a similar effect, significantly increasing the production of androstenone glucuronide but to a lesser degree. Butyrate increased production ranging from 40 ± 2.2% to 5±1.5% (P &amp;lt; 0.05), propionate from 38 ± 3.6% to 3 ± 2.6% (P &amp;lt; 0.05), acetate and butyrate from 61±3.9% to 1 ± 2.8% (P &amp;lt; 0.05), acetate and propionate from 70±3.5% to 5±1.7% (P &amp;lt; 0.05), and butyrate and propionate from 82 ± 2.5% to 4 ± 1.1% (P &amp;lt; 0.05) when compared with the control. In conclusion, this trial provided evidence that SCFAs produced by the microbial fermentation of fiber can significantly increase hepatic androstenone metabolism in some animals, with a wide range in these effects among individual boars. Future research will involve assessing the effects of SCFAs on hepatic skatole metabolism.

Unlocking the power of short-chain fatty acids in ameliorating intestinal mucosal immunity: a new porcine nutritional approach.

Short-chain fatty acids (SCFAs), a subset of organic fatty acids with carbon chains ranging from one to six atoms in length, encompass acetate, propionate, and butyrate. These compounds are the endproducts of dietary fiber fermentation, primarily catalyzed by the glycolysis and pentose phosphate pathways within the gut microbiota. SCFAs act as pivotal energy substrates and signaling molecules in the realm of animal nutrition, exerting a profound influence on the intestinal, immune system, and intestinal barrier functions. Specifically, they contibute to 60-70% of the total energy requirements in ruminants and 10-25% in monogastric animals. SCFAs have demonstrated the capability to effectively modulate intestinal pH, optimize the absorption of mineral elements, and impede pathogen invasion. Moreover, they enhance the expression of proteins associated with intestinal tight junctions and stimulate mucus production, thereby refining intestinal tissue morphology and preserving the integrity of the intestinal structure. Notably, SCFAs also exert anti-inflammatory properties, mitigating inflammation within the intestinal epithelium and strengthening the intestinal barrier's defensive capabilities. The present review endeavors to synthesize recent findings regarding the role of SCFAs as crucial signaling intermediaries between the metabolic activities of gut microbiota and the status of porcine cells. It also provides a comprehensive overview of the current literature on SCFAs' impact on immune responses within the porcine intestinal mucosa.

O88 REDUCTION IN SYSTOLIC BLOOD PRESSURE FOLLOWING DIETARY FIBRE INTERVENTION IS DEPENDENT ON BASELINE GUT MICROBIOTA COMPOSITION

Background/Objective: Dietary interventions high in fibre have been shown to lower blood pressure (BP). This effect is via the gut microbiota, via fermentation of fibre and production of metabolites called short-chain fatty acids (SCFAs). Not all patients respond to dietary fibre interventions for unclear reasons. We aimed to determine if we can identify fibre-responders based on their gut microbiota and production of SCFAs. Methods: We performed a phase II cross-over placebo-controlled randomised clinical trial in untreated hypertensive patients. Twenty treatment-naive participants with hypertension received 40 g per day of fermentable fibre delivered as acetylated and butyrylated high amylose maize starch (HAMSAB) or the placebo for 3 weeks. Blood pressure was monitored at baseline and endpoint by ambulatory BP monitoring, with those experiencing a reduction of ≥2 mmHg in systolic BP classified as responders. The microbiota was determined by sequencing the V4-V5 region of the 16S rRNA gene in baseline stool samples. The relationship between baseline gut microbiota and response to dietary intervention was assessed with the MaAsLin2 package. Plasma SCFAs levels were quantified by mass spectrometry. Results: We observed a placebo-subtracted mean 24-hour systolic BP of –6.1 mmHg (p=0.03, reported in Jama et al., 2023 Nature Cardiovascular Research), with 14 (70%) individuals classified as responders and 6 (30%) as non-responders. Genera significantly enriched in responders included Dialister (β=1.29, q=1.921x10-134), Coprococcus (β=1.26, q=3.282x10-121), Bifidobacterium (β=1.67, q=1.11x10-81), Ruminococcus (β=0.161, q=1.11x10-8), and Roseburia (β=0.82, q=4.275x10-2). Responders also produced higher levels of the SCFAs butyrate (mean±SEM, non-responders 4.95±2.4 vs responders 51.15±14.7, p=0.0096), but no difference in other SCFAs. Conclusions: Participants who experienced a decrease in systolic BP following a dietary fibre intervention had increased bacterial genera known to contain species that produce SCFAs (Bifidobacterium, Roseburia, Ruminococcus) at baseline, and were able to produce more butyrate. These data suggest that baseline microbiota composition contributes to the response to dietary fibre intervention trials in people with hypertension, likely via increased capacity to produce butyrate.

P016 METAPROTEOMICS ANALYSIS IN HEALTHY INDIVIDUALS REVEALS A HIGH CARDIOVASCULAR RISK PROFILE ACROSS BLOOD PRESSURE, DIET, HUMAN AND MICROBIAL PROTEINS

Background/Objective: The gut microbiota is a crucial link between diet and cardiovascular health by producing beneficial metabolites, such as short-chain fatty acids (SCFAs), through fibre fermentation. However, most studies have focused on microbial DNA to infer microbiota function. Here, we employed metaproteomics, a novel method to capture gut human and microbiota protein expression profiles concurrently. We aimed to investigate the crosstalk between gut microbiota, diet, host gut health, and blood pressure (BP). Methods: Mass spectrometry-based metaproteomic analysis was performed on 61 faecal samples with paired ambulatory BP monitoring, food intake (food frequency questionnaire), and demographic data. Results: We identified 21,594 microbial and 1,072 human proteins. Traditional risk factors (age, BMI, sex, BP) explained only ∼10% of the proteome variance. However, unsupervised clustering analysis of both human and microbial proteome revealed two distinct clusters (low-risk and high-risk) with significantly different 24-hour systolic BP (mean±SD, low-risk 116±13mmHg vs high-risk: 126±15mmHg, P=0.016), women prevalence (72.4% vs 40.6%, P=0.025), and diet quality (assessed as Athlete Diet Index, 61.6±6.7 vs 57.8±7.6, P=0.044). In the human proteome, the low-risk group had lower expression of the VEGFA-VEGFR2 signalling pathway and tight junction proteins and higher SCFA production (particularly propionate), suggesting an anti-inflammatory gut environment. In the microbial proteome, the low-risk group had higher activity of inorganic ion transport and metabolism-related proteins, with increased expression of acetate kinase that produces both the SCFAs acetate and propionate, particularly in primary fibre-fermenting bacteria, including Phocaeicola dorei and Blautia wexlerae. Finally, via co-expression networks, we identified profilin-1 (PFN1), which contributes to hypertension and atherosclerosis, as a crucial human protein associated with several bacteria present in the high-risk group. Conclusions: Employing an unsupervised clustering based on human and microbial proteomics, we identified two groups of participants with varying traditional and emerging cardiovascular risk factors. This was explained by complex interactions among diet, gut microbiota, and BP. This underscores the need for sophisticated models to understand multifactorial risk factors for cardiovascular disease.