Marked gut microbiota dysbiosis and increased imidazole propionate are associated with a NASH Göttingen Minipig model.

BACKGROUND: Gut microbiota dysbiosis is associated with the development of non-alcoholic steatohepatitis (NASH) through modulation of gut barrier, inflammation, lipid metabolism, bile acid signaling and short-chain fatty acid production. The aim of this study was to describe the impact of a choline-deficient amino acid defined high fat diet (CDAHFD) on the gut microbiota in a male Göttingen Minipig model and on selected pathways implicated in the development of NASH. RESULTS: Eight weeks of CDAHFD resulted in a significantly altered colon microbiota mainly driven by the bacterial families Lachnospiraceae and Enterobacteriaceae, being decreased and increased in relative abundance, respectively. Metabolomics analysis revealed that CDAHFD decreased colon content of short-chain fatty acid and increased colonic pH. In addition, serum levels of the microbially produced metabolite imidazole propionate were significantly elevated as a consequence of CDAHFD feeding. Hepatic gene expression analysis showed upregulation of mechanistic target of rapamycin (mTOR) and Ras Homolog, MTORC1 binding in addition to downregulation of insulin receptor substrate 1, insulin receptor substrate 2 and the glucagon receptor in CDAHFD fed minipigs. Further, the consequences of CDAHFD feeding were associated with increased levels of circulating cholesterol, bile acids, and glucagon but not total amino acids. CONCLUSIONS: Our results indicate imidazole propionate as a new potentially relevant factor in relation to NASH and discuss the possible implication of gut microbiota dysbiosis in the development of NASH. In addition, the study emphasizes the need for considering the gut microbiota and its products when developing translational animal models for NASH.

Effect of flow and peristaltic mixing on bacterial growth in a gut-like channel.

The ecology of microbes in the gut has been shown to play important roles in the health of the host. To better understand microbial growth and population dynamics in the proximal colon, the primary region of bacterial growth in the gut, we built and applied a fluidic channel that we call the "minigut." This is a channel with an array of membrane valves along its length, which allows mimicking active contractions of the colonic wall. Repeated contraction is shown to be crucial in maintaining a steady-state bacterial population in the device despite strong flow along the channel that would otherwise cause bacterial washout. Depending on the flow rate and the frequency of contractions, the bacterial density profile exhibits varying spatial dependencies. For a synthetic cross-feeding community, the species abundance ratio is also strongly affected by mixing and flow along the length of the device. Complex mixing dynamics due to contractions is described well by an effective diffusion term. Bacterial dynamics is captured by a simple reaction-diffusion model without adjustable parameters. Our results suggest that flow and mixing play a major role in shaping the microbiota of the colon.

Impact of an oligosaccharide-based polymer on the metabolic profiles and microbial ecology of weanling pigs experimentally infected with a pathogenic E. coli.

BACKGROUND: Our previous study has reported that supplementation of oligosaccharide-based polymer enhances gut health and disease resistance of pigs infected with enterotoxigenic E. coli (ETEC) F18 in a manner similar to carbadox. The objective of this study was to investigate the impacts of oligosaccharide-based polymer or antibiotic on the host metabolic profiles and colon microbiota of weaned pigs experimentally infected with ETEC F18. RESULTS: Multivariate analysis highlighted the differences in the metabolic profiles of serum and colon digesta which were predominantly found between pigs supplemented with oligosaccharide-based polymer and antibiotic. The relative abundance of metabolic markers of immune responses and nutrient metabolisms, such as amino acids and carbohydrates, were significantly differentiated between the oligosaccharide-based polymer and antibiotic groups (q < 0.2 and fold change > 2.0). In addition, pigs in antibiotic had a reduced (P < 0.05) relative abundance of Lachnospiraceae and Lactobacillaceae, whereas had greater (P < 0.05) Clostridiaceae and Streptococcaceae in the colon digesta on d 11 post-inoculation (PI) compared with d 5 PI. CONCLUSIONS: The impact of oligosaccharide-based polymer on the metabolic and microbial profiles of pigs is not fully understood, and further exploration is needed. However, current research suggest that various mechanisms are involved in the enhanced disease resistance and performance in ETEC-challenged pigs by supplementing this polymer.

Colon Drug Delivery Systems Based on Swellable and Microbially Degradable High-Methoxyl Pectin: Coating Process and In Vitro Performance.

Oral colon delivery systems based on a dual targeting strategy, harnessing time- and microbiota-dependent release mechanisms, were designed in the form of a drug-containing core, a swellable/biodegradable polysaccharide inner layer and a gastroresistant outer film. High-methoxyl pectin was employed as the functional coating polymer and was applied by spray-coating or powder-layering. Stratification of pectin powder required the use of low-viscosity hydroxypropyl methylcellulose in water solution as the binder. These coatings exhibited rough surfaces and higher thicknesses than the spray-coated ones. Using a finer powder fraction improved the process outcome, coating quality and inherent barrier properties in aqueous fluids. Pulsatile release profiles and reproducible lag phases of the pursued duration were obtained from systems manufactured by both techniques. This performance was confirmed by double-coated systems, provided with a Kollicoat® MAE outer film that yielded resistance in the acidic stage of the test. Moreover, HM pectin-based coatings manufactured by powder-layering, tested in the presence of bacteria from a Crohn's disease patient, showed earlier release, supporting the role of microbial degradation as a triggering mechanism at the target site. The overall results highlighted viable coating options and in vitro release characteristics, sparking new interest in naturally occurring pectin as a coating agent for oral colon delivery.

The Effects of Temperature and Humidity Index on Growth Performance, Colon Microbiota, and Serum Metabolome of Ira Rabbits.

This study investigates the effects of different THI values on growth performance, intestinal microbes, and serum metabolism in meat rabbits. The results showed that there were significant differences in THI in different location regions of the rabbit house. The high-THI group (HG) could significantly reduce average daily gain and average daily feed intake in Ira rabbits (p < 0.05). The low-THI group (LG) significantly increased the relative abundance of Blautia (p < 0.05). The HG significantly increased the relative abundance of Lachnospiraceae NK4A136 group and reduced bacterial community interaction (p < 0.05). The cytokine-cytokine receptor interactions, nuclear factor kappa B signaling pathway, and toll-like receptor signaling pathway in each rabbit's gut were activated when the THI was 26.14 (p < 0.05). Metabolic pathways such as the phenylalanine, tyrosine, and tryptophan biosynthesis and phenylalanine metabolisms were activated when the THI was 27.25 (p < 0.05). Meanwhile, the TRPV3 and NGF genes that were associated with heat sensitivity were significantly upregulated (p < 0.05). In addition, five metabolites were found to be able to predict THI levels in the environment with an accuracy of 91.7%. In summary, a THI of 26.14 is more suitable for the growth of meat rabbits than a THI of 27.25, providing a reference for the efficient feeding of meat rabbits.

Evaluation of Four Multispecies Probiotic Cocktails in a Human Colonic Fermentation Model.

Bacteriotherapy represents an attractive approach for both prophylaxis and treatment of human diseases. However, combining probiotic bacteria in "cocktails" is underexplored, despite its potential as an alternative multi-target therapy. Herein, three-strain probiotic mixtures containing different combinations of Bacillus (Bc.) coagulans [ATB-BCS-042], Levilactobacillus (Lv.) brevis [THT 0303101], Lacticaseibacillus (Lc.) paracasei [THT 031901], Bacillus subtilis subsp. natto [ATB-BSN-049], Enterococcus faecium [ATB-EFM-030], and Bifidobacterium (Bf.) animalis subsp. lactis [THT 010802] were prepared. Four cocktails (PA: Bc. coagulans + Lv. brevis + Lc. paracasei, PB: Bc. subtilis subsp. natto + Lv. brevis + Lc. paracasei, PC: E. faecium + Lv. brevis + Lc. paracasei, PD: Bc. coagulans + Lv. brevis + Bf. animalis subsp. lactis) were tested using a short-term (72 h) simulation of the human colonic microbiota in a final dose of 6 × 109 CFU. All these probiotic mixtures significantly increased butyrate production compared to the parallel control experiment. PA and PB promoted a bifidogenic effect and facilitated lactobacilli colonization. Furthermore, reporter gene assays using the AhR_HT29-Lucia cell line revealed that fermentation supernatants from PA and PB notably induced AhR transactivity. Subsequent examination of the metabolic outputs of PA and PB in intestinal epithelial models using cell culture inserts suggested no significant impact on the transepithelial electrical resistance (TEER). Assessment of the expression of proinflammatory and anti-inflammatory cytokines, as well as AhR-related target genes in the Caco-2 cell monolayers indicated that PB's metabolic output upregulated most of the measured endpoints. This in vitro investigation evaluated the potential impact of four multispecies probiotic mixtures in the human colonic microbiota and identified a promising formulation comprising a combination of Bc. subtilis subsp. natto, Lv. brevis, and Lc. paracasei as a promising formulation for further study.

Trace amounts of antibiotic altered metabolomic and microbial profiles of weaned pigs infected with a pathogenic E. coli.

BACKGROUND: Our previous study has shown that supplementation of trace amounts of antibiotic exacerbated the detrimental effects of enterotoxigenic E. coli (ETEC) infection and delayed the recovery of pigs that may be associated with modified metabolites and metabolic pathways. Therefore, the objective of this study was to explore the impacts of trace levels of antibiotic (carbadox) on host metabolic profiles and colon microbiota of weaned pigs experimentally infected with ETEC F18. RESULTS: The multivariate analysis highlighted a distinct metabolomic profile of serum and colon digesta between trace amounts of antibiotic (TRA; 0.5 mg/kg carbadox) and label-recommended dose antibiotic (REC; 50 mg/kg carbadox) on d 5 post-inoculation (PI). The relative abundance of metabolomic markers of amino acids, carbohydrates, and purine metabolism were significantly differentiated between the TRA and REC groups (q < 0.2). In addition, pigs in REC group had the highest (P < 0.05) relative abundance of Lactobacillaceae and tended to have increased (P < 0.10) relative abundance of Lachnospiraceae in the colon digesta on d 5 PI. On d 11 PI, pigs in REC had greater (P < 0.05) relative abundance of Clostridiaceae compared with other groups, whereas had reduced (P < 0.05) relative abundance of Prevotellaceae than pigs in control group. CONCLUSIONS: Trace amounts of antibiotic resulted in differential metabolites and metabolic pathways that may be associated with its slow responses against ETEC F18 infection. The altered gut microbiota profiles by label-recommended dose antibiotic may contribute to the promotion of disease resistance in weaned pigs.

Higher niacin intakes improve the lean meat rate of Ningxiang pigs by regulating lipid metabolism and gut microbiota.

As one of the local pig breeds in China with a high fat rate, improving the lean meat rate of Ningxiang pigs through nutritional intervention is an urgent issue to be solved. As an important feed additive, niacin plays an important role in lipid metabolism. The purpose of this study was to investigate the regulation and mechanism of niacin on fat deposition in Ningxiang pigs. Thirty-four Ningxiang pigs (53.34 ± 2.78 kg) were randomly divided into two groups with five replicates each, with three to four Ningxiang pigs per replicate. The control group was fed a basal diet (contained 22 mg/kg niacin), and the experimental group was fed the same diet supplemented with an additional 100 mg/kg of niacin. The experimental period lasted 60 days. One Ningxiang pig was selected for slaughter sampling for each replicate. This study found that lean meat percentage of Ningxiang pigs in the experimental group was significantly increased (P < 0.05), accompanied by a significant decrease in fat percentage (P < 0.05). 16S rRNA sequencing analysis found an abundance of Streptococcus in the experimental group (P < 0.05), along with significantly decreased levels of Lactobacillus (P < 0.05). The changes in some OTUs belonging to Firmicutes, Bacteroidota, and Actinobacteriota were closely related to the changes in the fat rate and lean meat rate of Ningxiang pigs (P < 0.05). LC-MS metabolomics analysis found that about 43.75% of the differential metabolites were related to lipids and lipid-like molecules in the liver (P < 0.05). Spearman's correlation analysis showed correlations between the carcass traits, microbiota, and liver metabolites. In conclusion, niacin improves lean meat percentage and reduces fat deposition by regulating lipid metabolism and gut microbiota composition in Ningxiang pigs.

Saffron against Neuro-Cognitive Disorders: An Overview of Its Main Bioactive Compounds, Their Metabolic Fate and Potential Mechanisms of Neurological Protection.

Saffron (Crocus sativus L.) is a spice used worldwide as a colouring and flavouring agent. Saffron is also a source of multiple bioactive constituents with potential health benefits. Notably, saffron displays consistent beneficial effects against a range of human neurological disorders (depression, anxiety, sleeping alterations). However, the specific compounds and biological mechanisms by which this protection may be achieved have not yet been elucidated. In this review, we have gathered the most updated evidence of the neurological benefits of saffron, as well as the current knowledge on the main saffron constituents, their bioavailability and the potential biological routes and postulated mechanisms by which the beneficial protective effect may occur. Our aim was to provide an overview of the neuroprotective effects attributed to this product and its main bioactive compounds and to highlight the main research gaps that need to be further pursued to achieve full evidence and understanding of the benefits of saffron. Overall, improved clinical trials and adequately designed pre-clinical studies are needed to support the evidence of saffron and of its main bioactive components (e.g., crocin, crocetin) as a therapeutic product to combat neurological disorders.

Supplementation of a lacto-fermented rapeseed-seaweed blend promotes gut microbial- and gut immune-modulation in weaner piglets.

BACKGROUND: The direct use of medical zinc oxide in feed will be abandoned after 2022 in Europe, leaving an urgent need for substitutes to prevent post-weaning disorders. RESULTS: This study investigated the effect of using rapeseed-seaweed blend (rapeseed meal added two brown macroalgae species Ascophylum nodosum and Saccharina latissima) fermented by lactobacilli (FRS) as feed ingredients in piglet weaning. From d 28 of life to d 85, the piglets were fed one of three different feeding regimens (n = 230 each) with inclusion of 0%, 2.5% and 5% FRS. In this period, no significant difference of piglet performance was found among the three groups. From a subset of piglets (n = 10 from each treatment), blood samples for hematology, biochemistry and immunoglobulin analysis, colon digesta for microbiome analysis, and jejunum and colon tissues for histopathological analyses were collected. The piglets fed with 2.5% FRS manifested alleviated intraepithelial and stromal lymphocytes infiltration in the gut, enhanced colon mucosa barrier relative to the 0% FRS group. The colon microbiota composition was determined using V3 and V1-V8 region 16S rRNA gene amplicon sequencing by Illumina NextSeq and Oxford Nanopore MinION, respectively. The two amplicon sequencing strategies showed high consistency between the detected bacteria. Both sequencing strategies indicated that inclusion of FRS reshaped the colon microbiome of weaned piglets with increased Shannon diversity. Prevotella stercorea was verified by both methods to be more abundant in the piglets supplied with FRS feed, and its abundance was positively correlated with colonic mucosa thickness but negatively correlated with blood concentrations of leucocytes and IgG. CONCLUSIONS: FRS supplementation relieved the gut lymphocyte infiltration of the weaned piglets, improved the colon mucosa barrier with altered microbiota composition. Increasing the dietary inclusion of FRS from 2.5% to 5% did not lead to further improvements.

Colon Microbiocenosis and Its Correction in Patients Receiving Programmed Hemodialysis.

The aim of the investigation was to study the species composition of colon microbiocenosis in patients with chronic kidney disease receiving programmed hemodialysis treatment and to evaluate the efficacy of its correction using a new immobilized synbiotic. MATERIALS AND METHODS: Samples of colon microbiota from 62 patients undergoing programmed hemodialysis were studied before and after a course of diet therapy that included probiotic components, in particular, the immobilized synbiotic LB-complex L. Isolation of microorganisms was carried out according to our original method; for bacteria identification, a MALDI-TOF Autoflex speed mass spectrometer (Bruker Daltonik, Germany) was used in the Biotyper program mode. The results were assessed using the criteria proposed by the authors and based on the OST 91500.11.0004-2003. The efficacy of the immobilized synbiotic was determined based on the clinical data, questionnaires, and bacteriological tests. RESULTS: In patients receiving programmed hemodialysis (before the start of the diet therapy), chronic moderate inflammation and azotemia were found. Dysbiotic changes in microbiocenosis were revealed in all the examined patients; in the absence or suppression of lacto- and bifidoflora, the number and diversity of Bacteroides spp., Clostridium spp., Collinsella spp., Eggerthella spp. and other bacteria increased, which was consistent with the theory of functional redundancy of gut microbiota. From the answers to the questionnaires, a decrease in the quality of life was found (up to 70 points out of 100) according to six of the eight scales used. After the combined therapy using the synbiotic LB-complex L in the study group, 56% of the examined patients showed their microbiocenosis restored to normal; no grade III dysbiosis was detected in any patient. There was a significant decrease in CRP and ESR in these patients and an improvement in the quality of life by criteria reflecting physical health. CONCLUSION: In patients receiving programmed hemodialysis, the addition of a probiotic component in the diet therapy restores the evolutionarily determined structure of the microbiocenosis, normalizes its functions, and leads to an overall improvement in health and quality of life.

Low pathogenic avian influenza virus infection retards colon microbiota diversification in two different chicken lines.

BACKGROUND: A commensal microbiota regulates and is in turn regulated by viruses during host infection which can influence virus infectivity. In this study, analysis of colon microbiota population changes following a low pathogenicity avian influenza virus (AIV) of the H9N2 subtype infection of two different chicken breeds was conducted. METHODS: Colon samples were taken from control and infected groups at various timepoints post infection. 16S rRNA sequencing on an Illumina MiSeq platform was performed on the samples and the data mapped to operational taxonomic units of bacterial using a QIIME based pipeline. Microbial community structure was then analysed in each sample by number of observed species and phylogenetic diversity of the population. RESULTS: We found reduced microbiota alpha diversity in the acute period of AIV infection (day 2-3) in both Rhode Island Red and VALO chicken lines. From day 4 post infection a gradual increase in diversity of the colon microbiota was observed, but the diversity did not reach the same level as in uninfected chickens by day 10 post infection, suggesting that AIV infection retards the natural accumulation of colon microbiota diversity, which may further influence chicken health following recovery from infection. Beta diversity analysis indicated a bacterial species diversity difference between the chicken lines during and following acute influenza infection but at phylum and bacterial order level the colon microbiota dysbiosis was similar in the two different chicken breeds. CONCLUSION: Our data suggest that H9N2 influenza A virus impacts the chicken colon microbiota in a predictable way that could be targeted via intervention to protect or mitigate disease.

Impact of Dietary Supplementation of Lactic Acid Bacteria Fermented Rapeseed with or without Macroalgae on Performance and Health of Piglets Following Omission of Medicinal Zinc from Weaner Diets.

The feeding of medicinal zinc oxide (ZnO) to weaner piglets will be phased out after 2022 in Europe, leaving pig producers without options to manage post-weaning disorders. This study assessed whether rapeseed meal, fermented alone (FRM) or co-fermented with a single (Ascophylum nodosum; FRMA), or two (A. nodossum and Saccharina latissima; FRMAS) brown macroalagae species, could improve weaner piglet performance and stimulate intestinal development as well as maturation of gut microbiota in the absence of in-feed zinc. Weaned piglets (n = 1240) were fed, during 28-85 days of age, a basal diet with no additives (negative control; NC), 2500 ppm in-feed ZnO (positive control; PC), FRM, FRMA or FRMAS. Piglets fed FRM and FRMA had a similar or numerically improved, respectively, production performance compared to PC piglets. Jejunal villus development was stimulated over NC in PC, FRM and FRMAS (gender-specific). FRM enhanced colon mucosal development and reduced signs of intestinal inflammation. All fermented feeds and PC induced similar changes in the composition and diversity of colon microbiota compared to NC. In conclusion, piglet performance, intestinal development and health indicators were sustained or numerically improved when in-feed zinc was replaced by FRM.

In Vitro Methods to Study Colon Release: State of the Art and An Outlook on New Strategies for Better In-Vitro Biorelevant Release Media.

The primary focus of this review is a discussion regarding in vitro media for colon release, but we also give a brief overview of colon delivery and the colon microbiota as a baseline for this discussion. The large intestine is colonized by a vast number of bacteria, approximately 1012 per gram of intestinal content. The microbial community in the colon is complex and there is still much that is unknown about its composition and the activity of the microbiome. However, it is evident that this complex microbiota will affect the release from oral formulations targeting the colon. This includes the release of active drug substances, food supplements, and live microorganisms, such as probiotic bacteria and bacteria used for microbiota transplantations. Currently, there are no standardized colon release media, but researchers employ in vitro models representing the colon ranging from reasonable simple systems with adjusted pH with or without key enzymes to the use of fecal samples. In this review, we present the pros and cons for different existing in vitro models. Furthermore, we summarize the current knowledge of the colonic microbiota composition which is of importance to the fermentation capacity of carbohydrates and suggest a strategy to choose bacteria for a new more standardized in vitro dissolution medium for the colon.

Possible Metabolic Pathway of a Novel Bioactive Polysaccharide Extracted from Dendrobium aphyllum: An In Vivo Study.

Our previous study characterized the structure-associated immunomodulatory effects of an edible Dendrobium aphyllum polysaccharide (DAP), and the in vitro gastrointestinal digestions highlighted DAP could be digested by the GI tract in some extent. Therefore, the present study further explored the digestive properties in vivo to infer the metabolic pathway with health mice model. Results revealed that DAP-treated group showed slightly lower blood glucose levels and significantly higher (P < 0.05) enzyme activities, namely G6Pase and GDH with an increment of about 0.4 to 0.9 and 45 to 91 U/mL, respectively. Meanwhile, DAP up-regulated the expression of glucose transporters, GLUT1 and GLUT2 in the increment rates of 56.34% to 68.28% and 76.63% to 83.03%, in colon. Furthermore, the beneficial effects of DAP on colon were confirmed by the increment of four types short chain fatty acids and the health-promoting microbiota diversity. The above results successfully identify the metabolic pathways after the oral administration of bioactive DAP. PRACTICAL APPLICATION: The metabolic pathways of Dendrobium aphyllum polysaccharide, after artificially stimulated oral administration, were characterized. The most of the unabsorbed portion of DAP were utilized by the colon microbiota, resulting in the significantly increasing production of four health-promoting SCFAs. The unabsorbed portion of DAP upregulated the diversity of various beneficial microbiota genus, and meanwhile downregulated kinds of harmful microbiota genus.

Colon Microbiome of Pigs Fed Diet Contaminated with Commercial Purified Deoxynivalenol and Zearalenone.

Deoxynivalenol (DON) and zearalenone (ZEN) can seriously affect animal health, with potentially severe economic losses. Previous studies have demonstrated that gut microbiota plays a significant role in detoxification. We analyzed the colon contents from three groups of pigs (fed either a standard diet, or a diet with 8 mg/kg DON or ZEN). Bacterial 16S rRNA gene amplicons were obtained from the colon contents, and sequenced using next-generation sequencing on the MiSeq platform. Overall, 2,444,635 gene sequences were generated, with ≥2000 sequences examined. Firmicutes and Bacteroidetes were the dominant phyla in all three groups. The sequences of Lactobacillus, Megasphaera, and Faecalibacterium genera, and the unclassified Clostridiaceae family, represented more than 1.2% of the total, with significantly different abundances among the groups. Lactobacillus was especially more abundant in the DON (7.6%) and ZEN (2.7%) groups than in the control (0.2%). A total of 48,346 operational taxonomic units (OTUs) were identified in the three groups. Two OTUs, classified as Lactobacillus, were the most dominant in the DON and ZEN groups. The abundances of the remaining OTUs were also significantly different among the groups. Thus, the mycotoxin-contaminated feed significantly affected the colon microbiota, especially Lactobacillus, which was the most abundant. Therefore, we speculate that Lactobacillus plays a major role in detoxification of these mycotoxins.

Polysaccharide from fermented Momordica charantia L. with Lactobacillus plantarum NCU116 ameliorates type 2 diabetes in rats.

The influence of Lactobacillus plantarum-fermentation on the structure and anti-diabetic effects of Momordica charantia polysaccharides were evaluated. High-fat diet and streptozotocin-induced type 2 diabetic rats were administrated with polysaccharides from fermented and non-fermented Momordica charantia (FP and NFP) for 4 weeks. Fermentation affected the physicochemical characterization, monosaccharide composition, molecular weight, and viscosity of Momordica charantia polysaccharides. Treatment with FP significantly ameliorated hyperglycemia, hyperinsulinemia, hyperlipidemia, and oxidative stress in diabetic rats compared with NFP. Moreover, the diversity and abundance of gut microbiota (Lactococcus laudensis and Prevotella loescheii) in diabetic rats were notably increased by treatment with FP in comparison to NFP. Meanwhile, FP-treated diabetic rats exhibited more colonic short-chain fatty acids (SCFAs) and lower pH values than that in NFP-treated rats. Overall, Lactobacillus plantarum-fermentation could enhance the anti-diabetes effects of Momordica charantia polysaccharides in rats by modifying the structure of polysaccharides to optimize gut microbiota and heighten the production of SCFAs.

Fusobacterium's link to colorectal neoplasia sequenced: A systematic review and future insights.

AIM: To critically evaluate previous scientific evidence on Fusobacterium's role in colorectal neoplasia development. METHODS: Two independent investigators systematically reviewed all original scientific articles published between January, 2000, and July, 2017, using PubMed, EMBASE, and MEDLINE. A total of 355 articles were screened at the abstract level. Of these, only original scientific human, animal, and in vitro studies investigating Fusobacterium and its relationship with colorectal cancer (CRC) were included in the analysis. Abstracts, review articles, studies investigating other colonic diseases, and studies written in other languages than English were excluded from our analysis. Ninety articles were included after removing duplicates, resolving disagreements between the two reviewers, and applying the above criteria. RESULTS: Studies have consistently identified positive associations between Fusobacterium, especially Fusobacterium nucleatum (F. nucleatum), and CRC. Stronger associations were seen in CRCs proximal to the splenic flexure and CpG island methylator phenotype (CIMP)-high CRCs. There was evidence of temporality and a biological gradient, with increased F. nucleatum DNA detection and quantity along the traditional adenoma-carcinoma sequence and in CIMP-high CRC precursors. Diet may have a differential impact on colonic F. nucleatum enrichment; evidence suggests that high fiber diet may reduce the risk of a subset of CRCs that are F. nucleatum DNA-positive. Data also suggest shorter CRC and disease-specific survival with increased amount of F. nucleatum DNA in CRC tissue. The pathophysiology of enrichment of F. nucleatum and other Fusobacterium species in colonic tissue is unclear; however, the virulence factors and changes to the local colonic environment with disruption of the protective mucus layer may contribute. The presence of a host lectin (Gal-GalNAc) in the colonic epithelium may also mediate F. nucleatum attachment to CRC and precursors through interaction with an F. nucleatum protein, fibroblast activation protein 2 (FAP2). The clinical significance of detection or enrichment of Fusobacterium in colorectal neoplasia is ambiguous, but data suggest a procarcinogenic effect of F. nucleatum, likely due to activation of oncogenic and inflammatory pathways and modulation of the tumor immune environment. This is hypothesized to be mediated by certain F. nucleatum strains carrying invasive properties and virulence factors such as FadA and FAP. CONCLUSION: Evidence suggests a potential active role of Fusobacterium, specifically F. nucleatum, in CRC. Future prospective and experimental human studies would fill an important gap in this literature.

5-Fluorouracil and irinotecan (SN-38) have limited impact on colon microbial functionality and composition in vitro.

Gastrointestinal mucositis is a debilitating side effect of chemotherapy treatment, with currently no treatment available. As changes in microbial composition have been reported upon chemotherapy treatment in vivo, it is thought that gut microbiota dysbiosis contribute to the mucositis etiology. Yet it is not known whether chemotherapeutics directly cause microbial dysbiosis, thereby increasing mucositis risk, or whether the chemotherapeutic subjected host environment disturbs the microbiome thereby aggravating the disease. To address this question, we used the M-SHIME®, an in vitro mucosal simulator of the human intestinal microbial ecosystem, as an experimental setup that excludes the host factor. The direct impact of two chemotherapeutics, 5-fluorouracil (5-FU) and SN-38 (active metabolite of irinotecan), on the luminal and mucosal gut microbiota from several human donors was investigated through monitoring fermentation activity and next generation sequencing. At a dose of 10 µM in the mucosal environment, 5-FU impacted the functionality and composition of the colon microbiota to a minor extent. Similarly, a daily dose of 10 µM SN-38 in the luminal environment did not cause significant changes in the functionality or microbiome composition. As our mucosal model does not include a host-compartment, our findings strongly indicate that a putative microbial contribution to mucositis is initially triggered by an altered host environment upon chemotherapy.

Structure of Brewer's Spent Grain Lignin and Its Interactions with Gut Microbiota in Vitro.

Lignin is part of dietary fiber, but its conversion in the gastrointestinal tract is not well understood. The aim of this work was to obtain structural information on brewer's spent grain (BSG) lignin and to understand the behavior of the polymeric part of lignin exposed to fecal microbiota. The original BSG and different lignin fractions were characterized by pyrolysis-GC/MS with and without methylation. Methylation pyrolysis proved that the ratio between guaiacyl and syringyl units was similar in all lignin samples, but the ratio between p-coumaric and ferulic acids varied by the isolation method. Combined pyrolysis results indicated higher acylation of γ-OH groups in syringyl than in guaiacyl lignin units. The polymeric lignin structure in the alkali-soluble fraction after enzymatic hydrolysis was slightly altered in the in vitro colon fermentation, whereas lignin in the insoluble residue after enzymatic treatments remained intact.