Modulation of gut microbiota and metabolites by Flammulina velutipes polysaccharides during in vitro human fecal fermentation: Unveiling Bacteroides as a potential primary degrader.

Flammulina velutipes, a widely cultivated species of edible fungus, exhibits diverse functional activities attributed to its polysaccharides. In this study, we employed an in vitro model to investigate the impact of F. velutipes polysaccharides (FVP) fermentation on gut microbiota, with a particular focus on Bacteroides. FVP fermentation resulted in the proliferation of microbiota associated with short-chain fatty acid (SCFA) metabolism and suppression of Escherichia-Shigella. Bacteroides emerged as potential primary degraders of FVP, with species-level analysis identifying the preference of B. thetaiotaomicron and B. intestinalis in FVP degradation. Metabolomics analysis revealed significant increases in hypoxanthine and 7-methyladenine contents, with histidine metabolism emerging as the most enriched pathway. B. nordii and B. xylanisolvens exhibited the most influence on amino acid and SCFA metabolism. Understanding the mechanisms by which gut microbiota metabolize FVP can provide valuable insights into the potential of FVP to promote intestinal health and disease prevention.

Catabolism of phenolics from grape peel and its effects on gut microbiota during in vitro colonic fermentation.

BACKGROUND: Grape peels, the main by-products of wine processing, are rich in bioactive ingredients of phenolics, including proanthocyanidins, flavonoids and anthocyanins. Phenolics have the function of regulating intestinal microbiota and promoting intestinal health. From the perspective of the dietary nutrition of grape peel phenolics (GPP), this study was to investigate the influence of GPP on the composition and metabolism of human gut microbiota during in vitro fermentation. RESULTS: The results indicated that GPP could decrease pH and promote the production of short-chain fatty acids (SCFAs). ACE and Chao1 indices in GPP group were lower than that of the Blank group. GPP enhanced the levels of Lachnospiraceae UCG-004, Bacteroidetes, and Roseburia, but reduced the Firmicutes/Bacteroidetes ratio. KEGG enrichment pathways related to phenolic acid metabolism mainly included flavonoid, anthocyanin, flavone and flavonol biosynthesis. Gut microbiota could accelerate the release and breakdown of phenolic compounds, resulting in a decrease in the content of hesperetin-7-O-glucoside, delphinidin-3-O-glucoside, and cyanidin-3-rutinoside etc. In vitro antibacterial test found that GPP increased the diameters of the inhibition zones of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) in a dose-dependent manner. CONCLUSION: The above results revealed that GPP might be a potential prebiotic-like to prevent diseases by improving gut health. This study could provide theoretical basis for potential to exploit GPP as dietary nutrition to maintain intestinal function. This article is protected by copyright. All rights reserved.

Multispecies probiotics complex improves bile acids and gut microbiota metabolism status in an in vitro fermentation model.

The consumption of probiotics has been extensively employed for the management or prevention of gastrointestinal disorders by modifying the gut microbiota and changing metabolites. Nevertheless, the probiotic-mediated regulation of host metabolism through the metabolism of bile acids (BAs) remains inadequately comprehended. The gut-liver axis has received more attention in recent years due to its association with BA metabolism. The objective of this research was to examine the changes in BAs and gut microbiota using an in vitro fermentation model. The metabolism and regulation of gut microbiota by commercial probiotics complex containing various species such as Lactobacillus, Bifidobacterium, and Streptococcus were investigated. The findings indicated that the probiotic strains had produced diverse metabolic profiles of BAs. The probiotics mixture demonstrated the greatest capacity for Bile salt hydrolase (BSH) deconjugation and 7α-dehydroxylation, leading to a significant elevation in the concentrations of Chenodeoxycholic acid, Deoxycholic acidcholic acid, and hyocholic acid in humans. In addition, the probiotic mixtures have the potential to regulate the microbiome of the human intestines, resulting in a reduction of isobutyric acid, isovaleric acid, hydrogen sulfide, and ammonia. The probiotics complex intervention group showed a significant increase in the quantities of Lactobacillus and Bifidobacterium strains, in comparison to the control group. Hence, the use of probiotics complex to alter gut bacteria and enhance the conversion of BAs could be a promising approach to mitigate metabolic disorders in individuals.

Microbial-Transferred Metabolites and Improvement of Biological Activities of Green Tea Catechins by Human Gut Microbiota.

Green tea catechins (GTCs) are dietary polyphenols with broad bioactivities that undergo extensive microbial metabolism in the human gut. However, microbial-transferred metabolites and their health benefits are not fully understood. Herein, the microbial metabolism of GTCs by human fecal microbiota and dynamic alteration of the microbiota were integrally investigated via in vitro anaerobic fermentation. The results showed that the human gut microbiota exhibited a strong metabolic effect on GTCs via UHPLC-MS/MS analysis. A total of 35 microbial-transferred metabolites were identified, far more than were identified in previous studies. Among them, five metabolites, namely EGCG quinone, EGC quinone, ECG quinone, EC quinone, and mono-oxygenated EGCG, were identified for the first time in fermented GTCs with the human gut microbiota. Consequently, corresponding metabolic pathways were proposed. Notably, the antioxidant, α-amylase, and α-glucosidase inhibitory activities of the GTCs sample increased after fermentation compared to those of the initial unfermented sample. The results of the 16S rRNA gene sequence analysis showed that the GTCs significantly altered gut microbial diversity and enriched the abundancy of Eubacterium, Flavonifractor, etc., which may be further involved in the metabolisms of GTCs. Thus, these findings contribute to a better understanding of the interactions between GTCs and gut microbiota, as well as the health benefits of green tea consumption.

An In Vitro Colonic Fermentation Study of the Effects of Human Milk Oligosaccharides on Gut Microbiota and Short-Chain Fatty Acid Production in Infants Aged 0-6 Months.

The impact of five human milk oligosaccharides (HMOs)-2'-fucosyllactose (2FL), 3'-sialyllactose (3SL), 6'-sialyllactose (6SL), lacto-N-tetraose (LNT), and lacto-N-neotetraose (LNnT)-on the gut microbiota and short-chain fatty acid (SCFA) metabolites in infants aged 0-6 months was assessed through in vitro fermentation. Analyses of the influence of different HMOs on the composition and distribution of infant gut microbiota and on SCFA levels were conducted using 16S rRNA sequencing, quantitative real-time PCR (qPCR), and gas chromatography (GC), respectively. The findings indicated the crucial role of the initial microbiota composition in shaping fermentation outcomes. Fermentation maintained the dominant genera species in the intestine but influenced their abundance and distribution. Most of the 10 Bifidobacteria strains effectively utilized HMOs or their degradation products, particularly demonstrating proficiency in utilizing 2FL and sialylated HMOs compared to non-fucosylated neutral HMOs. Moreover, our study using B. infantis-dominant strains and B. breve-dominant strains as inocula revealed varying acetic acid levels produced by Bifidobacteria upon HMO degradation. Specifically, the B. infantis-dominant strain yielded notably higher acetic acid levels than the B. breve-dominant strain (p = 0.000), with minimal propionic and butyric acid production observed at fermentation's conclusion. These findings suggest the potential utilization of HMOs in developing microbiota-targeted foods for infants.

Structural changes of rice starch-anthocyanins complexes (V-type) and its impact on gut microbiotas and potential metabolic pathways during in vitro fermentation.

This study explored the differences in the in vitro fermentation properties of rice starch (RS) and rice starch-anthocyanins complexes (RS-A). Structural characterization suggested that RS and RS-A complexes showed a V-type crystalline structure. The degree of order (DO) and degree of double helix (DD) values of RS and RS-A complexes were enhanced after fermentation. Moreover, the RS-A complexes could improve the relative abundance of Bacteroidetes, Ruminococcaceae, and up-regulate gut microbiota diversity to maintain gut homeostasis. Relative abundance of potential metabolic pathways, such as energy metabolism, digestion system, and carbohydrate degradation overexpressed in the presence of RS-A complexes. The results demonstrated that the RS-A complexes had slower fermentation rates contributing to the transport of the formed short-chain fatty acid (SCFA) to the end of the colon and that the crystallinity might be a factor influencing the utilization of the starch matrix by the gut microbiota for SCFA formation.

Effect of lotus seed resistant starch on the bioconversion pathway of taurocholic acid by regulating the intestinal microbiota.

Taurocholic acid (TCA) is abundant in the rat intestine and has multiple health benefits. In the gut, intestinal microbiota can transform TCA into different bile acid (BA) derivatives, with the composition of microbiota playing a crucial role in the transformation process. This study aims to investigate how lotus seed resistant starch (LRS) can regulate microbiota to influence BA transformation. A fecal fermentation study was conducted in vitro, using either LRS, high-amylose maize starch (HAMS), or glucose (GLU) to analyze microbiota composition, BA content, and metabolic enzyme activities over different fermentation times. Bioinformatics analysis found that LRS increased the relative abundance of Enterococcus, Bacillus, and Lactobacillus, and decreased Escherichia-Shigella, compared with HAMS and GLU. LRS also reduced total BA content and accelerated the conversion of TCA to cholic acid, deoxycholic acid, and other derivatives. These results reveal that LRS and GLU tend to mediate the dehydroxy pathway, whereas HAMS tends to secrete metabolic enzymes in the epimerization pathway. Therefore, the evidence that LRS may regulate TCA bioconversion may benefit human colon health research and provide an important theoretical basis, as well as offer new concepts for the development of functional foods.

Metabolites of Clostridium leptum fermenting flaxseed polysaccharide alleviate obesity in rats.

Obesity is a chronic metabolic disease. Our previous research found flaxseed polysaccharide (FP) has an anti-obesity effect, and its anti-obesity effect possibly depends on Clostridium leptum (C. leptum). However, whether the strain takes the role and how it works is still being determined. Here, FP was fermented in vitro by C. leptum and its metabolites were analyzed. Subsequently, the FP fermentation broth of C. leptum (FPF) was given to the obese pseudo sterile rats. The results showed FPF was rich in various metabolites, among which the top ten in relative expression abundance were 3 beta-hydroxy-5-cholestenoate, 7,8-dihydro-3b,6a-dihydroxy-alpha-ionol 9-glucoside, Valyl-Serine, 2-amino-4-[(2-hydroxy-1-oxopropyl)amino]butanoic acid, Agavoside B, glycylproline, lycopersiconolide, armillaritin, Isoleucyl-Hydroxyproline and norethindrone acetate. After intervention with FPF, the weight, abdominal fat ratio, and total fat ratio of rats were significantly reduced and the lipid metabolism of them has been improved. This effect may be achieved by up regulating glucagon-like peptide-1 and adiponectin and further activating the AMP-activated protein kinase signaling pathway. This is the first experimental proof that FP exerts its anti-obesity effects through metabolites from C. leptum fermenting FP, not FP itself and the bacterial cells (debris) of C. leptum. It is also the first demonstration that FPF has a significant anti-obesity effect.

Treatment of corn with lactic acid delayed in vitro ruminal degradation without compromising fermentation: a biological and morphological monitoring study.

Grain processed by lactic acid (LA) is known to improve ruminant growth and health. However, the exact mechanism regarding rumen hydrolysis of LA-treated grain is still ambiguous. This experiment was designed to compare the effects of 5% LA treatment on the trophic and morphological variations in corn and to discover the alternations in ruminal hydrolysis between LA-treated and untreated corn macroscopically and microscopically using in vitro fermentation method. The results showed that, compared with untreated corn (CN), corn treated with 5% LA for 48 h (CNLA) experienced a decrease in the dry matter, albumin fraction, aNDFom, and water-soluble carbohydrate content but an increase in the resistant starch content. The in vitro fermentation showed that the pH of CNLA was higher, but dry matter disappearance was lower than that of CN. Most of the fermentation indices were unaffected, except for decreased iso-butyrate and iso-valerate. The abundances of total bacteria, Prevotella spp., Streptococcus bovis, and Selenomonas ruminantium were higher, but those of Ruminococcus flavefaciens and Ruminococcus albus were lower in CNLA than in CN. There were differences in the scanning electron micrographs between CNLA and CN after 3 h of fermentation. This study suggests that treating corn with LA for 48 h can induce changes in its nutrient composition and alter the bacterial flora during subsequent in vitro fermentation. These changes appeared to be crucial contributors to the beneficial effects observed in rumen fermentation.

The Pea Oligosaccharides Could Stimulate the In Vitro Proliferation of Beneficial Bacteria and Enhance Anti-Inflammatory Effects via the NF-κB Pathway.

The oligosaccharides extracted from the seeds of peas, specifically consisting of raffinose, stachyose, and verbascose, fall under the category of raffinose family oligosaccharides (RFOs). The effect of RFOs on intestinal microflora and the anti-inflammatory mechanism were investigated by in vitro fermentation and cell experiments. Firstly, mouse feces were fermented in vitro and different doses of RFOs (0~2%) were added to determine the changes in the representative bacterial community, PH, and short-chain fatty acids in the fermentation solution during the fermentation period. The probiotic index was used to evaluate the probiotic proliferation effect of RFOs and the optimal group was selected for 16S rRNA assay with blank group. Then, the effects of RFOs on the inflammatory response of macrophage RAW264.7 induced by LPS were studied. The activity of cells, the levels of NO, ROS, inflammatory factors, and the expression of NF-κB, p65, and iNOS proteins in related pathways were measured. The results demonstrated that RFOs exerted a stimulatory effect on the proliferation of beneficial bacteria while concurrently inhibiting the growth of harmful bacteria. Moreover, RFOs significantly enhanced the diversity of intestinal flora and reduced the ratio of Firmicutes-to-Bacteroides (F/B). Importantly, it was observed that RFOs effectively suppressed NO and ROS levels, as well as inflammatory cytokine release and expression of NF-κB, p65, and iNOS proteins. These findings highlight the potential of RFOs in promoting intestinal health and ameliorating intestinal inflammation.

In vitro fermentation characteristics of different types of fiber-rich ingredients by pig fecal inoculum.

BACKGROUND: Dietary fibers with varying physicochemical properties have different fermentation characteristics, which may differently impact host health. The present study aimed to determine the fermentation characteristics including gas production kinetics, short-chain fatty acids (SCFAs) production and microbial composition of different fibrous ingredients using in vitro fermentation by fecal microbiota. RESULTS: Sugar beet pule (SBP), wheat bran (WB), dried corn distillers grains with solubles (DDGS), rice bran (RB) and alfalfa meal (AM) were selected to fermentation in vitro for 36 h. The results showed that SBP had the greatest gas production. SBP had the highest in vitro dry matter fermentability (IVDMF) and production of acetate, propionate and total SCFAs, followed by WB, which were all greater than DDGS, AM and RB. The alpha-diversity was higher in the DDGS, AM and RB groups than in the WB and SBP groups. Differences in microbial community composition were observed among groups. The relative abundance of Treponema was highest in WB group. RB group showed lower Prevotella abundance than other groups but had higher Succinivibrio abundance. Interestingly, the Lactobacillus reached the highest abundances in the DDGS group. Correlation analysis indicated that the relative abundance of Treponema and Prevotella was positively associated with the gas production, IVDMF and SCFAs, whereas norank_f_Muribaculaceae, Rikenellaceae_RC9_gut_group, Lysinibacillus and Succinivibrio were the opposite. CONCLUSION: Collectively, WB and SBP were fermented rapidly by fecal microbiota compared to DDGS, AM and RB. Different fiber sources have different fiber compositions and fermentation properties that affect the microbial compositins and SCFAs production. © 2024 Society of Chemical Industry.

In vitro conversion of ellagic acid to urolithin A by different gut microbiota of urolithin metabotype A.

The metabolite urolithin A, a metabolite of the dietary polyphenol ellagic acid (EA), has significant health benefits for humans. However, studies on the gut microbiota involved in ellagic acid metabolism are limited. In this study, we conducted in vitro fermentation of EA using human intestinal microbiome combined with antibiotics (vancomycin, polymyxin B sulfate, and amphotericin B). Liquid chromatography-mass spectrometry (LC-MS/MS) analysis demonstrated that the production capacity of urolithin A by gut microbiota co-treated with polymyxin B sulfate and amphotericin B (22.39 µM) was similar to that of untreated gut microbiota (24.26 µM). Macrogenomics (high-throughput sequencing) was used to analyze the composition and structure of the gut microbiota. The results showed that the abundance of Bifidobacterium longum, Bifidobacterium adolescentis, and Bifidobacterium bifidum in the gut microbiota without antibiotic treatment or co-treated with polymyxin B sulfate and amphotericin B during EA fermentation was higher than that in other antibiotic treatment gut microbiota. Therefore, B. longum, B. adolescentis, and B. bifidum may be new genera involved in the conversion of EA to urolithin A. In conclusion, the study revealed unique interactions between polyphenols and gut microbiota, deepening our understanding of the relationship between phenolic compounds like EA and the gut microbiota. These findings may contribute to the development of gut bacteria as potential probiotics for further development. KEY POINTS: • Intestinal microbiome involved in ellagic acid metabolism. • Gram-positive bacteria in the intestinal microbiome are crucial for ellagic acid metabolism. • Bifidobacterium longum, Bifidobacterium adolescentis, and Bifidobacterium bifidum participate in ellagic acid metabolism.

Effects of acetyl groups on the prebiotic properties of glucomannan extracted from Artemisia sphaerocephala Krasch seeds.

This study explores the structural modification of glucomannan extracted from Artemisia sphaerocephala Krasch seeds (60S) to assess the impact of acetyl groups on its prebiotic characteristics. The structural changes were examined, with a focus on the degree of acetyl group substitution (DS). Both deacetylation and acetylation had limited influence on the molecular properties of 60S. Despite these modifications, the apparent viscosity of all samples remained consistently low. In vitro fermentation experiments revealed that Escherichia-Shigella decreased as DS increased, while Bacteroides ovatus was enriched. Acetylation had no significant impact on the utilization rate of 60S but led to a reduction in the production of propionic acid. Furthermore, untargeted metabolomics analysis confirmed the changes in propionic acid levels. Notably, metabolites such as N-acetyl-L-tyrosine, γ-muricholic acid, and taurocholate were upregulated by acetylated derivatives. Overall, acetyl groups are speculated to play a pivotal role in the prebiotic properties of 60S.

Structure characterization of an agavin-type fructan isolated from Polygonatum cyrtonema and its effect on the modulation of the gut microbiota in vitro.

The herbal medicine Polygonatum cyrtonema is highly regarded in China for its medicinal and dietary properties. However, further research is needed to elucidate the structure of its polysaccharide and understand how it promotes human health by modulating the gut microbiota. This study aims to investigate a homogeneous polysaccharide (PCP95-1-1) from Polygonatum cyrtonema and assess its susceptibility to digestion as well as its utilization by intestinal microbiota. The results confirmed that PCP95-1-1 is an agavin-type fructan, which possesses two fructose chains, namely ß-(2 â†’ 6) and ß-(2 â†’ 1) fructosyl-fructose, attached to the sucrose core, and has branches of ß-D-Fruf residues. Moreover, PCP95-1-1 demonstrated resistance to digestion and maintained its reducing sugar content throughout the digestive system, indicating it could reach the gut without being digested. In vitro fermentation of PCP95-1-1 significantly decreased the pH value (p < 0.05) while notably increasing the production of short-chain fatty acids (SCFAs), confirming its utilization by human gut microbiota. Additionally, PCP95-1-1 exhibited a significant ability (p < 0.05) to beneficial bacteria such as Megamonas and Bifidobacterium, while reducing the presence of facultative or conditional pathogens such as Escherichia-Shigella and Klebsiella at the genus level. Consequently, PCP95-1-1 has the potential to positively influence physical well-being by modulating the gut microbiota environment and can be developed as a functional food.

Subtle structural variations of resistant starch from whole cooked rice significantly impact metabolic outputs of gut microbiota.

While cooked rice is widely consumed as a whole food, the specific characteristics and impact of its resistant starch (RS) on gut microbiota are largely unexplored. In this study, three rice varieties with distinct starch molecular structures were used to prepare RS from cooked rice. All three types of RS had a crystalline structure characterized as B + V type, with the V type being the predominant crystalline polymorph. Distinct differences in chain-length distributions were observed among different RSs, with rapidly fermentable starch fractions comprising short amylopectin and long amylose chains, while the degrees of polymerization (DPs) âˆ¼ 10, 37, 65, and 105 fractions comprised the slowly fermentable starch. Jasmine rice RS showed the highest proportion of this slowly fermentable starch fraction, which appeared to be specifically utilized by Megasphaera_elsdenii_DSM_20460 OTU198. The fermentation of Jasmine RS resulted in the highest production of butyrate after 24 h, which was positively correlated with the relative abundance of Megasphaera_elsdenii_DSM_20460 OTU198. These findings collectively indicate that RS in cooked rice with a higher V type crystallinity and DPs âˆ¼ 10, 37, 65, and 105 fractions promote butyrate production and stimulate the growth of butyrate-producing bacteria in the human gut, thereby conferring beneficial effects on gut health.

Fennel seeds dietary inclusion as a sustainable approach to reduce methane production and improve nutrient utilization and ruminal fermentation.

Ruminants are considered a major producer of methane (CH4 ). Therefore, the present study aimed to determine the ability of dry fennel seeds to affect in vitro gas production and fermentation. Fennel seeds were included at 0% (Control), 0.5%, 1%, 1.5%, and 2% DM of a diet containing per kg DM: 500 g concentrate feed mixture, 400 g berseem hay, and 100 g of rice straw. The incubations lasted 48 h. Fennel seeds increased (P < 0.001) the asymptotic gas production and decreased its rate, while decreasing the production and proportion of CH4 (P < 0.05) and increased its rate. Moreover, fennel seed increased DM and neutral detergent fiber (P < 0.01) degradability, and increased total production of short-chain fatty acids, acetate, and propionate (P < 0.05). Compared to the control, fennel seeds increased (P < 0.01) metabolizable energy, partitioning factor, and microbial crude protein production. Overall, fennel seeds can be included up to 2% DM in ruminant diets as an environmentally friendly product in animal farming due to its ability to improve feed utilization, ruminal fermentation and while reducing CH4 production.

Characterization of Various Noncovalent Polyphenol-Starch Complexes and Their Prebiotic Activities during In Vitro Digestion and Fermentation.

This study explores the structural characterization of six noncovalent polyphenol-starch complexes and their prebiotic activities during in vitro digestion and fermentation. Ferulic acid, caffeic acid, gallic acid, isoquercetin, astragalin, and hyperin were complexed with sweet potato starch (SPS). The polyphenols exhibited high binding capacity (>70%) with SPS. A partial release of flavonoids from the complexes was observed via in vitro digestion, while the phenolic acids remained tightly bound. Molecular dynamics (MD) simulation revealed that polyphenols altered the spatial configuration of polysaccharides and intramolecular hydrogen bonds formed. Additionally, polyphenol-SPS complexes exerted inhibitory effects on starch digestion compared to gelatinized SPS, owing to the increase in resistant starch fraction. It revealed that the different complexes stimulated the growth of Lactobacillus rhamnosus and Bifidobacterium bifidum, while inhibiting the growth of Escherichia coli. Moreover, in vitro fermentation experiments revealed that complexes were utilized by the gut microbiota, resulting in the production of short-chain fatty acids and a decrease in pH. In addition, the polyphenol-SPS complexes altered the composition of gut microbiota by promoting the growth of beneficial bacteria and decreasing pathogenic bacteria. Polyphenol-SPS complexes exhibit great potential for use as a prebiotic and exert dual beneficial effects on gut microbiota.

Molecular Mechanisms Underlying the Effects of Small Intestinal Fermentation on Enhancement of Prebiotic Characteristics of Cellulose in the Large Intestine.

Knowledge about the prebiotic characteristics of cellulose by in vitro fermentation is not complete due to the neglect of small intestinal fermentation. This study investigated the effects of small intestinal fermentation on the prebiotic characteristics of cellulose in the large intestine and potential mechanisms through an approach of combined in vivo small intestinal fermentation and in vitro fermentation. The structural similarity between cellulose in feces and after processing by the approach of this study confirmed the validity of the approach employed. Results showed that small intestinal fermentation of cellulose increased both acetate and propionate content and enriched Corynebacterium selectively. Compared to in vitro fermentation after in vitro digestion of cellulose, the in vitro fermentation of cellulose after in vivo small intestinal fermentation produced higher contents of acetate and propionate as well as the abundance of probiotics like Ruminococcaceae_UCG-002, Blautia, and Bifidobaterium. The changes in the structural features of cellulose after in vivo small intestinal fermentation were more obvious than those after in vitro digestion, which may account for the greater production of short-chain fatty acids (SCFAs) and the abundance of probiotics. In summary, small intestinal fermentation enhanced the prebiotic characteristics of cellulose in the large intestine by predisrupting its structure.

Estimating the contribution of the porcine fecal core microbiota to metabolite production via mathematical modeling and in vitro fermentation.

The swine gut microbiota is a complex ecosystem found throughout the gastrointestinal tract, with multiple exchanges with the host and whose composition is linked to both external and internal factors, such as diet or breed. Diet, probiotic, or prebiotic interventions have been designed to boost beneficial host-microbiota interactions, such as the production of anti-inflammatory molecules, or the fermentation of otherwise undigested resources. In parallel, a smaller microbial population, shared among the same host species, independent of external or internal factors, has been described and defined as the "core microbiota." Therapies targeting the core microbiota could possibly lead to more precise and long-lasting effects. However, the metabolic role of the porcine core microbiota, especially in relation to the rest of the microbial community, is currently missing. We present here the first dynamic model of the porcine core microbiota, which we used to estimate the core-microbiota metabolite production and to forecast the effect of a synbiotic intervention targeting the core genera of the core microbiota. We developed a community model in which a total of 17 microbial groups were established based on culture-based information of representative species. First, the model parameters were estimated, and the resulting model simulations were compared favorably with in vitro experimentation. The model was then used to predict the microbial dynamics of the core and non-core members under different experimental conditions. Therefore, it was able to theorize the main-metabolite core microbiota contribution, hypothesizing that it could be mainly responsible for acetate and propionate, but not for butyrate production.IMPORTANCECurrently, little information is present in the literature to describe the generic metabolic role of the porcine core microbiota or to inform on the effect of interventions targeting the core genera. Moreover, both in vitro and in vivo experimentations aiming to explore the core microbiota dynamics are technically demanding, expensive, or restricted by ethical considerations. Modeling approaches can be used as an initial exploratory tool to develop hypotheses for targeted experimentation. Our mathematical model provides initial information on the microbial and metabolite dynamics of the core microbiota in relation to diet and therapeutic intervention.

Role of gut microbiota on regulation potential of Dendrobium officinale Kimura & Migo in metabolic syndrome: In-vitro fermentation screening and in-vivo verification in db/db mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Dendrobium officinale Kimura & Migo (DEN) is a traditional medicine in China since Han dynasty. Decoction of its stem is often used in the treatment of Type-II diabetes (T2D), which is a typical metabolic disease accompanied with the impaired metabolic function of blood glucose and lipid. AIM OF THE STUDY: Our study aimed to investigate the role of gut microbiota in differentiating DEN from different sources and its related pathway in the alleviation of metabolic syndromes induced by T2D. MATERIALS AND METHODS: The aqueous extracts of four commercially available Dendrobium (DEN-1∼4) were prepared and screened through an in-vitro fermentation system. Based on their alterations in monosaccharide composition and short chain fatty acids (SCFA) formation during fermentation with db/db faecal fluid, one DEN extract was selected for further in vivo verification. The selected Dendrobium (DEN-4) was orally administered to db/db mice for 16 days once daily at the dosage of 200 mg/kg followed by evaluating its effect on blood glucose level, liver function and intestinal microenvironment including alterations of intestinal integrity and gut microbiota composition. In addition, liver metabolomics analysis was employed to reveal the related metabolic pathways. RESULTS: Different extent of SCFA formation and utilization of monosaccharides were observed for the extracts of four DEN from different sources with a negative correlation between SCFA level and the ratio of Utilized glucose/Utilized mannose observed in the in-vitro fermentation system with db/db faecal fluid. DEN-4 with the highest SCFA formation during the in-vitro fermentation was selected and exhibited significantly hypoglycaemic effect in db/db mice with the alleviation of hepatic steatosis and impaired lipid homeostasis. Further mechanistic studies revealed that orally administered DEN-4 could improve the intestinal integrity of db/db mice via elevating their tight junction protein (ZO-1 and Occludin) expression in the colon and improve the diversity of gut microbiota with enhanced formation of SCFA. Moreover, metabolomics and KEGG pathway analysis of liver tissues suggested that the alleviated metabolic syndrome in db/db mice by DEN-4 might possibly be achieved through activation of PPAR pathway. CONCLUSION: Our current study not only revealed the potential of gut microbiota in differentiating DEN from different sources, but also demonstrated that DEN exhibited its beneficial effect on the T2D induced metabolic syndrome possibly through enhancement of intestinal integrity and activation of PPAR pathway via gut-liver axis in db/db mice.