Beneficial Short-chain Fatty Acids Research Articles

Fecal glycoprotein 2 is a marker of gut microbiota dysbiosis and systemic inflammation

BackgroundAntimicrobial autoantigenic glycoprotein 2 (GP2) is an important component of the innate immune system which originates from the exocrine pancreas as well as from the small intestines. The relationship of GP2 with the intestinal microbiome as well as the systemic implications of increased fecal GP2 levels are, however, still unclear. Therefore, fecal samples from 2,812 individuals of the Study of Health in Pomerania (SHIP) were collected to determine GP2 levels (enzyme-linked immunosorbent assay) and gut microbiota profiles (16 S rRNA gene sequencing). These data were correlated and associated with highly standardised and comprehensive phenotypic data of the study participants.ResultsFecal GP2 levels were increased in individuals with higher body mass index and smokers, whereas lower levels were found in case of preserved exocrine pancreatic function, female sex or a healthier diet. Moreover, higher GP2 levels were associated with increased serum levels of high-sensitivity C-reactive protein, loss of gut microbial diversity and an increase of potentially detrimental bacteria (Streptococcus, Haemophilus, Clostridium XIVa, or Collinsella). At the same time, predicted microbial pathways for the biosynthesis of beneficial short-chain fatty acids or lactic acid were depleted in individuals with high fecal GP2. Of note, GP2 exhibited a stronger association to overall microbiome variation than calprotectin.ConclusionFecal GP2 is a biomarker of gut microbiota dysbiosis and associated with increased systemic inflammation. The intestines may be more important as origin for GP2 than pancreatic acinar cells. Future studies need to investigate the potential clinical value in disease specific patient cohorts.

Action and cooperation in alginate degradation by three enzymes from the human gut bacterium Bacteroides eggerthii DSM 20697

Alginate is a polysaccharide consumed by humans in edible seaweed and different foods where it is applied as a texturizing hydrocolloid or in encapsulations of drugs and probiotics. While gut bacteria are found to utilize and ferment alginate to health beneficial short chain fatty acids, knowledge on details of the molecular reactions is sparse. Alginates are composed of mannuronic acid (M) and its C-5 epimer guluronic acid (G). An alginate related polysaccharide utilization locus (PUL) has been identified in the gut bacterium Bacteroides eggerthii DSM 20697. The PUL encodes two polysaccharide lyases (PLs) from the PL6 (BePL6) and PL17 (BePL17) families as well as a KdgF-like metalloprotein (BeKdgF) known to catalyze ring-opening of 4,5-unsaturated monouronates yielding 4-deoxy-l-erythro-5-hexoseulose uronate (DEH). B. eggerthii DSM 20697 does not grow on alginate, but readily proliferates with a lag phase of a few hours in the presence of an endo-acting alginate lyase A1-I from the marine bacterium Sphingomonas sp. A1. The B. eggerthii lyases are both exo-acting and while BePL6 is strictly G-block specific, BePL17 prefers M-blocks. BeKdgF retained 10−27% activity in the presence of 0.1−1 mM EDTA. X-ray crystallography was used to investigate the three-dimensional structure of BeKdgF, based on which a catalytic mechanism was proposed to involve Asp102, acting as acid/base having pKa of 5.9 as determined by NMR pH titration. BePL6 and BePL17 cooperate in alginate degradation with BeKdgF linearizing produced 4,5-unsaturated monouronates. Their efficiency of alginate degradation was much enhanced by addition of the A1-I alginate lyase.

Food carbohydrates in the gut: structural diversity, microbial utilization, and analytical strategies.

Carbohydrates, which are a vital dietary component, undergo digestion and gut fermentation through microbial enzymes to produce beneficial short-chain fatty acids. Certain carbohydrates selectively modulate the gut microbiota, impacting host health. Carbohydrate-active enzymes within the gut microbiota significantly contribute to carbohydrate utilization and microbial diversity. Despite their importance, the structural complexity of carbohydrates poses analytical challenges. However, recent advancements, notably, mass spectrometry, have allowed for their characterization and functional analysis. This review examines the intricate relationship between dietary carbohydrates and the gut microbiota, highlighting the crucial role of advanced analytical techniques in understanding their diversity and implications. These advancements provide valuable insights into carbohydrate bioactivity. Integrating high-throughput analysis with next-generation sequencing provides deeper insights into gut microbial interactions, potentially revealing which carbohydrate structures are beneficial for gut health.

Does the gut microbiome influence disc health and disease? The interplay between dysbiosis, pathobionts, and disc inflammation: a pilot study

BACKGROUND CONTEXTGut microbiome alterations resulting in inflammatory responses have been implicated in many distant effects on different organs. However, its influence on disc health is still not fully investigated. PURPOSEOur objective was to document the gut biome in healthy volunteers and patients with disc degeneration and to understand the role of gut dysbiosis on human disc health. STUDY DESIGNExperimental case-control study. PATIENT SAMPLEWe included 40 patients with disc degeneration (DG) and 20 healthy volunteers (HV). HV comprised of age groups 30 to 60 years with no known record of back pain and no clinical comorbidities, with normal MRI. Diseased group (DG) were patients in the same age group undergoing surgery for disc disease (disc herniation-25; discogenic stenosis-15) and without instability (with Modic-20; and non-Modic-20). OUTCOME MEASURESN/A. METHODSWe analyzed 16S V3-V4 rDNA gut metagenome from 20 healthy volunteers (HV) and compared the top signature genera from 40 patients with disc degeneration (DG) across Modic and non-Modic groups. Norgen Stool DNA Kit was used for DNA extraction from ∼200 mg of each faecal sample collected using the Norgen Stool Collection Kit.16S V3-V4 rDNA amplicons were generated with universal bacterial primers 341F and 806R and amplified with Q5 High-Fidelity DNA Polymerase. Libraries were sequenced with 250×2 PE to an average of 0.1 million raw reads per sample (Illumina Novaseq 6000). Demultiplexed raw data was assessed with FastQC, and adapter trimmed reads >Q30 reads were processed in the QIME2 pipeline.Serum C-reactive protein (CRP) was measured by the immunoturbimetry method and Fatty acid-binding protein 5 (FABP5) was measured in albumin-globulin-depleted plasma through global proteome analysis. RESULTSWe observed significant gut dysbiosis between HV and DG and also between the Modic and non-Modic groups. In the Modic group, commensals Bifidobacterium and Ruminococcus were significantly depleted, while pathobionts Streptococcus, Prevotella, and Butryvibrio were enriched. Firmicutes/Bacteroidetes ratio was decreased in DG (Modic-0.62, non-Modic-0.43) compared to HV (0.70). Bacteria-producing beneficial short-chain fatty acids were also depleted in DG. Elevated serum CRP and increased FABP5 were observed in DG. CONCLUSIONThe study revealed gut dysbiosis, an altered Firmicutes/Bacteroidetes ratio, reduced SCFA-producing bacteria, and increased systemic and local inflammation in association with disc disease, especially in Modic changes. The findings have considerable importance for our understanding and prevention of disc degeneration.

Abstract 2794: Consumption of dietary fiber correlates with a significant increase in a-diversity in the intestinal Microbiome of allo-HCT recipients and with lower GVHD-lethality in pre-clinical models

Abstract Background: Graft-versus-host disease (GVHD) is associated with a decrease in intestinal microbiota and beneficial short-chain fatty acids (SCFAs). Dietary fiber can modulate the intestinal microbiome and SCFA production which effect intestinal epithelium health and immunity. Therefore, we hypothesized that a high-fiber diet in recipients of an allogeneic hematopoietic cell transplantation (allo-HCT) could result in an increase of beneficial commensals, concentrations of SCFAs, and decreased risk of GVHD. Methods: We evaluated dietary data and fecal samples of allo-HCT patients receiving unmodified grafts (n=95) at MSKCC (day -10 to day +30 relative to allo-HCT) and correlated microbial α-diversity (16s rRNA, n=568 samples) with fiber intake and acute GVHD in No-GVHD (n=30), Non-LGI-GVHD (GVHD except lower gastrointestinal tract, n=41), and LGI-GVHD patients (lower gastrointestinal tract GVHD, n=24).We tested concentrations of cellulose fiber (0%, 6%, 12% and 40%) in a GVHD mouse model (C57BL/6J into BALB/c) to assess survival, microbial composition (shotgun sequencing n=180; n=30 per group), cecal SCFAs concentrations (GC-MS n=24, n=8 per group), and lastly, T cell subsets (Th1/Th17/Tregs) and colonic epithelial MHC-II expression (flow cytometry n=54, n=18 per group). Results: In allo-HCT patients, fiber intake correlated positively with microbial α-diversity (R=0.3, p=0.04), especially in the LGI-GVHD group (p=0.007). Additionally, patients with high fiber intake had higher microbial α-diversity compared to the low fiber cohort (p<0.0001).GVHD mice receiving a fiber-rich diet (12%), compared to 0% and 6%, had a higher microbial α-diversity (p=0.01); reduced GVHD lethality (p=0.02); and a decrease in the Enterococcus sp. (p=0.004) and Akkermansia sp. (p=0.01) abundance; taxa which are associated with worse overall survival and increased risk of lethal GVHD. In contrast, compared to 12%, the 40% fiber diet resulted in worse survival (p=0.002), lower α-diversity (p=0.05) and a higher abundance of Bifidobacterium sp. (p<0.0001).Cecal butyrate in GVHD mice was higher in response to the 12% vs. the 0% (p=0.01) and 6% (p=0.05) fiber diets. Mice treated with12% fiber displayed higher number of Tregs (CD4+CD25+FOXP3+), than those with 0% (p=0.001) and 6% (p=0.02); and a lower expression of MHC-II in epithelial cells (EpCAM+CD45-) vs. 0% fiber (p=0.02). Conclusions: We demonstrated that a higher fiber intake in allo-HCT patients is associated with an increase in α-diversity; especially in LGI-GVHD patients. In a pre-clinical GVHD-model, optimal fiber consumption (12% cellulose) leads to an increase in α-diversity, a decrease in pathogen relative abundance, increased T-regulatory cells, and a decrease in GVHD lethality. These results suggest that dietary fiber could be utilized to prevent GVHD. Citation Format: Jenny Paredes, Anqi Dai, Ruben J. Faustino Ramos, Peter Adintori, Teng Fei, Chi Nguyen, Harold Elias, Kristen Victor, Romina Ghale, Charlotte Pohl, Ana Gradissimo, Justin Cross, Oriana Miltiadous, Jonathan Peled, Marina Burgos da Silva, Marcel RM van den Brink. Consumption of dietary fiber correlates with a significant increase in a-diversity in the intestinal Microbiome of allo-HCT recipients and with lower GVHD-lethality in pre-clinical models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2794.

Ameliorative effect of an acidic polysaccharide from Phellinus linteus on ulcerative colitis in a DSS-induced mouse model

Phellinus linteus, a rare medicinal fungus, displays strong antitumor and anti-inflammatory activities because of its active metabolites, particularly polysaccharides. We investigated effects of P. linteus acidic polysaccharide (PLAP) on amelioration of dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) in a mouse model, and associated mechanisms. PLAP treatment alleviated major UC symptoms (weight loss, reduced food intake, increased disease activity index), and ameliorated histopathological colon tissue damage, reduced levels of pro-inflammatory factors (TNF-α, IL-6, IL-1β), enhanced anti-inflammatory factor IL-10 level, reduced levels of oxidative stress-related enzymes iNOS and MPO, and enhanced expression of tight junction proteins (ZO-1, occludin, claudin-1). qPCR analysis revealed that PLAP downregulated phosphorylation levels of p65 and p38 and transcriptional level of TLR-4. High-throughput sequencing showed that PLAP restored gut microbiota diversity and species abundances in the UC model, and gas chromatographic analysis showed that it increased levels of beneficial short-chain fatty acids. Our findings indicate that PLAP has strong potential for development as an anti-UC agent based on its reduction of inflammation and oxidative stress levels, modulation of gut microbiota composition, and promotion of normal intestinal barrier function.

Prebiotic inulin ameliorates SARS-CoV-2 infection in hamsters by modulating the gut microbiome

Current treatment options for COVID-19 are limited, with many antivirals and immunomodulators restricted to the most severe cases and preventative care limited to vaccination. As the SARS-CoV-2 virus and its increasing variants threaten to become a permanent fixture of our lives, this new reality necessitates the development of cost-effective and accessible treatment options for COVID-19. Studies have shown that there are correlations between the gut microbiome and severity of COVID-19, especially with regards to production of physiologically beneficial short-chain fatty acids (SCFAs) by gut microbes. In this study, we used a Syrian hamster model to study how dietary consumption of the prebiotic inulin affected morbidity and mortality resulting from SARS-CoV-2 infection. After two weeks of observation, we discovered that inulin supplementation attenuated morbid weight loss and increased survival rate in hamster subjects. An analysis of microbiome community structure showed significant alterations in 15 genera. Notably, there were also small increases in fecal DCA and a significant increase in serum DCA, perhaps highlighting a role for this secondary bile acid in conferring protection against SARS-CoV-2. In light of these results, inulin and other prebiotics are promising targets for future investigation as preventative treatment options for COVID-19.

Microbial ensemble in the hives: deciphering the intricate gut ecosystem of hive and forager bees of Apis mellifera.

The gut microbiome of honey bees significantly influences vital traits and metabolic processes, including digestion, detoxification, nutrient provision, development, and immunity. However, there is a limited information is available on the gut bacterial diversity of western honey bee populations in India. This study addresses the critical knowledge gap and outcome of which would benefit the beekeepers in India. This study investigates the gut bacterial diversity in forager and hive bees of Indian Apis mellifera, employing both culture-based and culture-independent methods. In the culturable study, a distinct difference in gut bacterial alpha and beta diversity between forager and hive bees emerges. Firmicutes, Proteobacteria, and Actinobacteria dominate, with hive bees exhibiting a Firmicutes-rich gut (65%), while foragers showcase a higher proportion of Proteobacteria (37%). Lactobacillus in the hive bee foregut aligns with the findings by other researchers. Bacterial amplicon sequencing analysisreveals a more intricate bacterial composition with 18 identified phyla, expanding our understanding compared to culturable methods. Hive bees exhibit higher community richness and diversity, likely due to diverse diets and increased social interactions. The core microbiota includes Snodgrassella alvi, Gilliamella apicola, and Bombilactobacillus mellis and Lactobacillus helsingborgensis, crucial for digestion, metabolism, and pathogen resistance. The study emphasises bacteria's role in pollen and nectar digestion, with specific groups like Lactobacillus and Bifidobobacterium spp. associated with carbohydrate metabolism and polysaccharide breakdown. These microbes aid in starch and sucrose digestion, releasing beneficial short-chain fatty acids. This research highlights the intricate relationship between honey bees and their gut microbiota, showcasing how the diverse and complex microbiome helps bees overcome dietary challenges and enhances overall host health. Understanding these interactions contributes to bee ecology knowledge and has implications for honey bee health management, emphasising the need for further exploration and conservation efforts.

Protein combined with certain dietary fibers increases butyrate production in gut microbiota fermentation.

The modern diet delivers nearly equal amounts of carbohydrates and protein into the colon representing an important protein increase compared to past higher fiber diets. At the same time, plant-based protein foods have become increasingly popular, and these sources of protein are generally less digestible than animal protein sources. As a result, a significant amount of protein is expected to reach the colon and be available for fermentation by gut microbiota. While studies on diet-microbiota interventions have mainly focused on carbohydrate fermentation, limited attention has been given to the role of protein or protein-fiber mixtures as fermentation substrates for the colonic microbiota. In this study, we aimed to investigate: (1) how changing the ratio of protein to fiber substrates affects the types and quantities of gut microbial metabolites and bacteria; and (2) how the specific fermentation characteristics of different types of fiber might influence the utilization of protein by gut microbes to produce beneficial short chain fatty acids. Our results revealed that protein fermentation in the gut plays a crucial role in shaping the overall composition of microbiota communities and their metabolic outputs. Surprisingly, butyrate production was maintained or increased when fiber and protein were combined, and even when pure protein samples were used as substrates. These findings suggest that indigestible protein in fiber-rich substrates may promote the production of microbial butyrate perhaps including the later stages of fermentation in the large intestine.

The effects of dairy on the gut microbiome and symptoms in gastrointestinal disease cohorts: a systematic review.

Bovine dairy foods provide several essential nutrients. Fermented bovine dairy foods contain additional compounds, increasing their potential to benefit gastrointestinal health. This review explores the effects of dairy consumption on the gut microbiome and symptoms in gastrointestinal disease cohorts. Human subjects with common gastrointestinal diseases (functional gastrointestinal disorders and inflammatory bowel disease) or associated symptoms, and equivalent animal models were included. A systematic literature search was performed using PubMed, Embase and Web of Science. The search yielded 3014 studies in total, with 26 meeting inclusion criteria, including 15 human studies (1550 participants) and 11 animal studies (627 subjects). All test foods were fermented bovine dairy products, primarily fermented milk and yogurt. Six studies reported increases in gastrointestinal bacterial alpha diversity, with nine studies reporting increases in relative Lactobacillus and Bifidobacterium abundance. Six studies reported increases in beneficial short-chain fatty acids, while three reported decreases. Gastrointestinal symptoms, specifically gut comfort and defecation frequency, improved in 14 human studies. Five animal studies demonstrated reduced colonic damage and improved healing. This review shows fermented bovine dairy consumption may improve gut microbial characteristics and gastrointestinal symptoms in gastrointestinal disease cohorts. Further human intervention studies are needed, expanding test foods and capturing non-self-reported gastrointestinal measures.

Interrelation between gut microbiota, SCFA, and fatty acid composition in pigs.

The gut microbiota is a key player in the host metabolism. Some bacteria are able to ferment non-digestible compounds and produce short-chain fatty acids that the host can later transform and accumulate in tissue. In this study, we aimed to better understand the relationships between the microorganisms and the short-chain fatty acid composition of the rectal content, including the possible linkage with the fatty acid composition in backfat and muscle of the pig. We studied a Duroc × Iberian crossbred population, and we found significant correlations between different bacterial and archaeal genera and the fatty acid profile. The abundance of n-butyric acid in the rectal content was positively associated with Prevotella spp. and negatively associated with Akkermansia spp., while conversely, the abundance of acetic acid was negatively and positively associated with the levels of Prevotella spp. and Akkermansia spp., respectively. The most abundant genus, Rikenellaceae RC9 gut group, had a positive correlation with palmitic acid in muscle and negative correlations with stearic acid in backfat and oleic acid in muscle. These results suggest the possible role of Prevotella spp. and Akkermansia spp. as biomarkers for acetic and n-butyric acids, and the relationship of Rikenellaceae RC9 gut group with the lipid metabolism, building up the potential, although indirect, role of the microbiota in the modification of the backfat and muscle fatty acid composition of the host.IMPORTANCEThe vital role of the gut microbiota on its host metabolism makes it essential to know how its modulation is mirrored on the fatty acid composition of the host. Our findings suggest Prevotella spp. and Akkermansia spp. as potential biomarkers for the levels of beneficial short-chain fatty acids and the possible influence of Rikenellaceae RC9 gut group in the backfat and muscle fatty acid composition of the pig.

New insight into pectic fractions of cell wall: Impact of extraction on pectin structure and in vitro gut fermentation

Pectic polysaccharides modulate gut fermentation ability, which is determined by structural characteristics. In this work, apple pectins were extracted by HCl (HAEP), NaOH (AEP), cellulase (EAEP), and in parallel cell wall pectic fractions were sequentially extracted by water (WEP), chelator (CEP) and NaOH (NEP). The aim is to comprehensively compare the impact of extraction on pectin structure and gut fermentation behavior. Results showed that high content of galacturonic acid (90.65 mol%) and large molecular weight (675 kg/mol) were detected in the HAEP. Molecular morphology of the HAEP presented high linearity, while AEP, EAEP and WEP exhibited compact filamentous structures with highly branched patterns. The AEP was characterized by high yield (33.1 g/100 g d.b.), moderate molecular weight (304 kg/mol) and large extent of rhamnogalacturonan-I region (24.88 %) with low degree of branching (1.77). After in vitro simulated gut fermentation for 24 h, total content of short-chain fatty acid (SCFA) generated with the AEP supplement increased to 36.8 mmol/L, followed by EAEP, HAEP and WEP (25.2, 24.2 and 20.3 mmol/L, respectively). Meanwhile, WEP simultaneously produced the highest ammonia content (22.4 mmol/L). This investigation suggests that the fermentation of AEP produces more beneficial SCFA and less ammonia, thus indicating a better gut fermentation property.

Human gut microbiome and metabolite dynamics under simulated microgravity

ABSTRACT The Artificial Gravity Bed Rest – European Space Agency (AGBRESA) study was the first joint bed rest study by ESA, DLR, and NASA that examined the effect of simulated weightlessness on the human body and assessed the potential benefits of artificial gravity as a countermeasure in an analog of long-duration spaceflight. In this study, we investigated the impact of simulated microgravity on the gut microbiome of 12 participants during a 60-day head-down tilt bed rest at the :envihab facilities. Over 60 days of simulated microgravity resulted in a mild change in the gut microbiome, with distinct microbial patterns and pathway expression in the feces of the countermeasure group compared to the microgravity simulation-only group. Additionally, we found that the countermeasure protocols selectively increased the abundance of beneficial short-chain fatty acids in the gut, such as acetate, butyrate, and propionate. Some physiological signatures also included the modulation of taxa reported to be either beneficial or opportunistic, indicating a mild adaptation in the microbiome network balance. Our results suggest that monitoring the gut microbial catalog along with pathway clustering and metabolite profiling is an informative synergistic strategy to determine health disturbances and the outcome of countermeasure protocols for future space missions.

Creating high-resistant starch rice by simultaneous editing of SS3a and SS3b.

Creating high-resistant starch rice by simultaneous editing of SS3a and SS3b.

Bacillus megaterium Renuspore® as a potential probiotic for gut health and detoxification of unwanted dietary contaminants.

Exposure to diverse environmental pollutants and food contaminants is ever-increasing. The risks related to the bioaccumulation of such xenobiotics in the air and food chain have exerted negative effects on human health, such as inflammation, oxidative stress, DNA damage, gastrointestinal disorders, and chronic diseases. The use of probiotics is considered an economical and versatile tool for the detoxification of hazardous chemicals that are persistent in the environment and food chain, potentially for scavenging unwanted xenobiotics in the gut. In this study, Bacillus megaterium MIT411 (Renuspore®) was characterized for general probiotic properties including antimicrobial activity, dietary metabolism, and antioxidant activity, and for the capacity to detoxify several environmental contaminants that can be found in the food chain. In silico studies revealed genes associated with carbohydrate, protein and lipid metabolism, xenobiotic chelation or degradation, and antioxidant properties. Bacillus megaterium MIT411 (Renuspore®) demonstrated high levels of total antioxidant activities, in addition to antimicrobial activity against Escherichia coli, Salmonella enterica, Staphylococcus aureus, and Campylobacter jejuni in vitro. The metabolic analysis demonstrated strong enzymatic activity with a high release of amino acids and beneficial short-chain fatty acids (SCFAs). Moreover, Renuspore® effectively chelated the heavy metals, mercury and lead, without negatively impacting the beneficial minerals, iron, magnesium, or calcium, and degraded the environmental contaminants, nitrite, ammonia, and 4-Chloro-2-nitrophenol. These findings suggest that Renuspore® may play a beneficial role in supporting gut health metabolism and eliminating unwanted dietary contaminants.

A263 MODULATION OF THE GUT MICROBIOTA TO PREVENT LOCAL ANASTOMOTIC TUMORS AND DISTANT METASTASIS IN COLORECTAL CANCER SURGERY

Abstract Background Colorectal cancer (CRC) recurrence is a leading cause of mortality worldwide. It has been suggested that poor anastomotic healing and leakage (AL) after surgery allows cancer cells to implant at the anastomotic site thereby increasing the risk of local cancer recurrence and metastatic spread in the peritoneum and to extraintestinal organs. We have previously showed that inulin, a well-known prebiotic, improves anastomotic healing and strengthens the gut barrier. Purpose The objective of the this study was to investigate the relationship between the promotion of postoperative intestinal healing using inulin and local and distant cancer recurrence. Method A 10-years' retrospective review of AL and non-AL cases after CRC surgery was performed in our institution. The effect of dietary supplementation with inulin on the occurrence of local anastomotic tumors was assessed in a mouse model inoculated with tumor cells directly in the gut lumen after colonic surgery. We also investigated in mice whether inulin may prevent metastatic spread and growth of tumor cells in the liver by transplanting CRC cells surgically into the spleen. Result(s) Patients experiencing AL displayed significantly lower overall survival and more cancer recurrence and progression compared to non-AL patients. Poor anastomotic healing in mice led to larger anastomotic tumors and peritoneal cancer dissemination. Inulin supplementation significantly inhibited local tumor implantation at the anastomotic site, and metastatic spread to the peritoneum and liver. Inulin increased the production of beneficial short-chain fatty acids, reinforced the gut barrier function and alleviated systemic inflammation in mice. Conclusion(s) Anastomotic leak was associated with worse oncological outcomes in patients and mice. Inulin was shown to reinforce the gut barrier, decrease the implantation of cancer cells at the anastomosis, and to prevent tumor dissemination and progression of liver metastasis. This paves the way toward future clinical trials in which such supplementation may be used to promote better oncological outcomes. Please acknowledge all funding agencies by checking the applicable boxes below CIHR, Other Please indicate your source of funding; CRS, FRQS Disclosure of Interest None Declared

In vitro and in silico assessment of probiotic and functional properties of Bacillus subtilis DE111®.

Bacillus subtilis DE111® is a safe, well-tolerated commercially available spore-forming probiotic that has been clinically shown to support a healthy gut microbiome, and to promote digestive and immune health in both adults and children. Recently it was shown that this spore-forming probiotic was capable of germinating in the gastrointestinal tract as early as 3 h after ingestion. However, a better understanding of the mechanisms involved in the efficacy of DE111® is required. Therefore, the present investigation was undertaken to elucidate the functional properties of DE111® through employing a combination of in vitro functional assays and genome analysis. DE111® genome mining revealed the presence of several genes encoding acid and stress tolerance mechanisms in addition to adhesion proteins required to survive and colonize harsh gastrointestinal environment including multi subunit ATPases, arginine deiminase (ADI) pathway genes (argBDR), stress (GroES/GroEL and DnaK/DnaJ) and extracellular polymeric substances (EPS) biosynthesis genes (pgsBCA). DE111® harbors several genes encoding enzymes involved in the metabolism of dietary molecules (protease, lipases, and carbohyrolases), antioxidant activity and genes associated with the synthesis of several B-vitamins (thiamine, riboflavin, pyridoxin, biotin, and folate), vitamin K2 (menaquinone) and seven amino acids including five essential amino acids (threonine, tryptophan, methionine, leucine, and lysine). Furthermore, a combined in silico analysis of bacteriocin producing genes with in vitro analysis highlighted a broad antagonistic activity of DE111® toward numerous urinary tract, intestinal, and skin pathogens. Enzymatic activities included proteases, peptidases, esterase's, and carbohydrate metabolism coupled with metabolomic analysis of DE111® fermented ultra-high temperature milk, revealed a high release of amino acids and beneficial short chain fatty acids (SCFAs). Together, this study demonstrates the genetic and phenotypic ability of DE111® for surviving harsh gastric transit and conferring health benefits to the host, in particular its efficacy in the metabolism of dietary molecules, and its potential to generate beneficial SCFAs, casein-derived bioactive peptides, as well as its high antioxidant and antimicrobial potential. Thus, supporting the use of DE111® as a nutrient supplement and its pottential use in the preparation of functional foods.

Voglibose Regulates the Secretion of GLP-1 Accompanied by Amelioration of Ileal Inflammatory Damage and Endoplasmic Reticulum Stress in Diabetic KKAy Mice.

Voglibose is an α-glycosidase inhibitor that improves postprandial hyperglycemia and increases glucagon-like peptide-1 (GLP-1) secretion in patients with type 2 diabetes. Recently, there has been increasing interest in the anti-inflammatory effects of voglibose on the intestine, but the underlying mechanism is not clear. This study evaluated the effects and mechanisms of voglibose on glycemic control and intestinal inflammation. Type 2 diabetic KKAy mice were treated with voglibose (1 mg/kg) by oral gavage once daily. After 8 weeks, glucose metabolism, levels of short-chain fatty acids (SCFAs), systematic inflammatory factors, intestinal integrity and inflammation were evaluated using hematoxylin and eosin staining, immunohistochemistry, immunofluorescence and Western blot analysis. Voglibose ameliorated glucose metabolism by enhancing basal- and glucose-dependent GLP-1 secretion. Several beneficial SCFAs, such as acetic acid and propionic acid, were increased by voglibose in the fecal sample. Additionally, voglibose notably decreased the proportion of pro-inflammatory macrophages and the expression of nuclear factor kappa B but increased the expression of tight junction proteins in the ileum, thus markedly improving intestinal inflammatory damage and reducing the systematic inflammatory factors. Ileal genomics and protein validation suggested that voglibose attenuated inositol-requiring protein 1α-X-box binding protein 1-mediated endoplasmic reticulum stress (ERS). Together, these results showed that voglibose enhanced the secretion of GLP-1, which contributed to the glycemic control in KKAy mice at least in part by regulating intestinal inflammation and the expression of ERS factors.

Effect of Lactobacillus with Feruloyl Esterase-Producing Ability on Dextran Sodium Sulfate-Induced Ulcerative Colitis in Mice.

Ulcerative colitis (UC) is becoming an increasingly serious health problem. This study aimed to investigate the effect of a newly isolated Lactobacillus species that produces feruloyl esterase (FAEb) on dextran sodium sulfate (DSS)-induced UC in mice. In this study, FAEb supplementation slowed body weight loss and mitigated colon length shortening, the severity of fecal occult blood, and increases in the disease activity index (DAI) in UC model mice. FAEb supplementation was also shown to reduce the expression of proinflammatory factors, increase the antioxidant capacity, improve the production of beneficial short-chain fatty acids (SCFAs), upregulate the expression of tight junction proteins, reduce the histopathological scores, and reduce mucous barrier damage in the gut. Furthermore, FAEb supplementation was shown to inhibit inflammatory NF-κB signaling pathway activity, increase the abundance of beneficial bacteria, and regulate the balance of microbiota in the gut. These results suggest that FAEb may serve as a potential probiotic to prevent and treat UC.

Pressurized hot water extraction, structural properties, biological effects, and in vitro microbial fermentation characteristics of sweet tea polysaccharide

Although sweet tea is rich in bioactive polysaccharides, the knowledge regarding their structures, bioactivities, and gut microbial metabolism is still limited. Therefore, in order to promote the application of sweet tea polysaccharide (STP) in the food industry, the pressurized hot water extraction (PHWE) of STP was optimized, and its structural properties and biological effects as well as microbial fermentation characteristics were investigated. The maximum extraction yield (4.64 % ± 0.03 %) of STP extracted by PHWE was obtained under the optimal conditions. Both homogalacturonan and arabinogalactan might exist as major polysaccharide fragments in STP. Additionally, STP exerted obviously in vitro antioxidant, anti-diabetic, and immunostimulatory effects, which might be related to its chemical properties, such as uronic acids, conjugated polyphenolics, and esterification degree. Furthermore, STP could be consumed by intestinal microbiota, and its fermentability was about 54 % at the end stage of fecal fermentation. Indeed, STP could modulate the microbial composition via improving the growth of several beneficial microbes, causing the release of beneficial short-chain fatty acids. Collectively, the findings indicate that the PHWE is an efficient method for extracting bioactive polysaccharides from sweet tea, and results can also provide a scientific basis for developing STP into functional foods or functional ingredients.