Metabolism Of Short-chain Fatty Acids Research Articles

ZiBuPiYin Recipe Prevented and Treated Cognitive Decline in ZDF Rats With Diabetes-Associated Cognitive Decline via Microbiota-Gut-Brain Axis Dialogue.

Gut microbiota is becoming one of the key determinants in human health and disease. Shifts in gut microbiota composition affect cognitive function and provide new insights for the prevention and treatment of neurological diseases. Diabetes-associated cognitive decline (DACD) is one of the central nervous system complications of type 2 diabetes mellitus (T2DM). ZiBuPiYin recipe (ZBPYR), a traditional Chinese medicine (TCM) formula, has long been used for the treatment of T2DM and prevention of DACD. However, the contribution of ZBPYR treatment to the interaction between the gut microbiota and metabolism for preventing and treating DACD remains to be clarified. Here, we investigate whether the gut microbiota plays a key role in ZBPYR-mediated prevention of DACD and treatment of T2DM via incorporating microbiomics and metabolomics, and investigate the links between the microbiota–gut–brain axis interaction and the efficacy of ZBPYR in ZDF rats. In the current study, we found that ZBPYR treatment produced lasting changes in gut microbiota community and metabolites and remotely affected hippocampus metabolic changes, thereby improving memory deficits and reversing β-amyloid deposition and insulin resistance in the brain of ZDF rats from T2DM to DACD. This may be related to a series of metabolic changes affected by gut microbiota, including alanine, aspartic acid, and glutamic acid metabolism; branched-chain amino acid metabolism; short-chain fatty acid metabolism; and linoleic acid/unsaturated fatty acid metabolism. In summary, this study demonstrates that prevention and treatment of DACD by ZBPYR partly depends on the gut microbiota, and the regulatory effects of bacteria-derived metabolites and microbiota–gut–brain axis are important protective mechanisms of ZBPYR.

Synergistic effects of exercise and catalase overexpression on gut microbiome.

Exercise influences metabolic parameters in part by modulating redox stress and as recently suggested, by affecting the gut microbiome. However, whether excess endogenous antioxidant potentiates or interferes with the beneficial effects of exercise on the gut microbiome is not known. A comparison of the gut microbiome of C57Bl6 (C57/WT) mice to the 'stress-less' catalase overexpressing mice models ([Tg(CAT)± ] and Bob-Cat), that were either exercised or remained sedentary, showed differences in both alpha and beta diversity. The significant variation was explained by genotypes along with exercise, suggesting a synergistic relationship between exercise and genotypic traits. Linear discriminant analysis effect size (LEfSe) analysis also revealed differential taxa within the exercised/genotype cohorts in contrast to those within sedentary/genotype cohorts. Functional pathway predictions from PICRUSt2 showed enrichment for the metabolism of short-chain fatty acids, butanoate and propanoate pathways in exercised groups. Spearman correlations between enriched taxa and metabolic parameters showed correlations with body or fat weight in some of the cohorts. However, there were significant correlations of differential taxa among all cohorts against parameters that predict energy metabolism, such as respiratory exchange ratio and energy expenditure. Overall, our study showed that there was a synergistic beneficial influence of antioxidant overexpression and exercise on the gut microbiome.

Aloe polysaccharides ameliorate acute colitis in mice via Nrf2/HO-1 signaling pathway and short-chain fatty acids metabolism

Aloe polysaccharides (APs) are acetyl polysaccharides. It has been reported APs could protect mice from ulcerative colitis (UC), but the complex interactions between APs and the intestinal barrier were unclear. Here, we investigated the relationship between APs and UC, and determined the synergistic effects of Nrf2/HO-1 signaling pathway and short-chain fatty acids (SCFAs) metabolism on protecting intestinal barrier in acute UC mice. Results showed APs could scavenge free radicals in vitro. In vivo, APs had the antioxidant and anti-inflammatory effect both in serum and colon. Besides, the pathological results showed APs could alleviate colonic lesions. Furthermore, our study indicated treatment with APs effectively increased SCFAs production. The inhibition of acute UC in mice was correlated with the APs-mediated effects on improving the expression of ZO-1, occludin, Nrf2, HO-I, and NQO1. Thus, APs effectively promoted the intestinal barrier via Nrf2/HO-1 signaling pathway and SCFAs metabolism, effectively ameliorating acute colitis in mice.

Lactobacillus strains derived from human gut ameliorate metabolic disorders via modulation of gut microbiota composition and short-chain fatty acids metabolism.

Regulation on gut microbiota and short-chain fatty acids (SCFAs) are believed to be a pathway to suppress the development of metabolic syndrome. In this study, three Lactobacillus strains derived from the human gut were investigated for their effects on alleviation of metabolic disorders. These strains were individually administered to metabolic disorder rats induced by high-fat-high-sucrose (HFHS) diet. Each strain exhibited its own characteristics in attenuating the impaired glucose-insulin homeostasis, hepatic oxidative damage and steatosis. Correlation analysis between SCFAs and host metabolic parameters suggested that Lactobacillus protective effects on metabolic disorders are partly mediated by recovery of SCFAs production, especially the faecal acetic acid. Correspondingly, it indicated that probiotics restore the gut microbiota dysbiosis in different extent, thereby protect against metabolic disorders in a manner that is associated with microbiota, but not totally reverse the changed composition of microbiota to the normal state. Thus, Lactobacillus strains partly protect against diet-induced metabolic syndrome by microbiota modulation and acetate elevation.

A homogeneous polysaccharide from Lycium barbarum: Structural characterizations, anti-obesity effects and impacts on gut microbiota

Lycium barbarum polysaccharides (LBPs) are known for their beneficial effects on diabetes, NAFLD and related chronic metabolic diseases induced by high-fat diet (HFD). However, the relevant researches are mainly about the whole crude polysaccharides, the specific active ingredient of LBPs and its bioactivity have been rarely explored. Herein, a homogeneous polysaccharide (LBP-W) was isolated and purified from crude LBPs. Structure characterizations indicated that LBP-W contained a main chain consisting of a repeated unit of →6)-β-Galp(1 → residues with branches composed of α-Araf, β-Galp and α-Rhap residues at position C-3. The objective of this study was to evaluate the anti-obesogenic effect of LBP-W and figure out the underlying mechanisms. In vivo efficacy trial illustrated that LBP-W supplements can alleviate HFD-induced mice obesity significantly. Gut microbiota analysis showed that LBP-W not only improved community diversity of intestinal flora, but also regulated their specific genera. Moreover, LBP-W can increase the content of short-chain fatty acids (SCFAs), a metabolite of the intestinal flora. In summary, all these results demonstrated that the homogeneous polysaccharide purified from L. barbarum could be used as a prebiotic agent to improve obesity by modulating the composition of intestinal flora and the metabolism of SCFAs.

Dechlorane Plus exposure on gut microbiome evaluated by using both in vivo and in vitro assays

The gut microbiome is crucial for the health of animals including human and is sensitive to environmental factors. Dechlorane Plus (DP) is a widely used polychlorinated flame retardant in commercial products for which general human population has been exposed to, but its effects on the gut microbiota are largely unknown. In this work, experiments were conducted to examine the effect of DP exposure on the intestinal microbiota by using Sprague-Dawley rats and a simulator of the human intestinal microbial ecosystem (SHIME). 16S rRNA gene high-throughput sequencing revealed that DP exposure in vivo reduced the relative abundance of the genera Prevotella, Quinella, and Ruminococcus, exposure in vitro decreased the relative abundance of Coriobacteriaceae, Parabacteroides, Bilophila, Sporolactobacillus, and Klebsiella. The phyla Synergistetes and Lentisphaerae were only detected in the descending colon. DP exposure also increased the concentrations of short-chain fatty acids (SCFAs) produced by the gut microbe both in vivo and in vitro, but SCFA metabolism was gradually inhibited as the increase of DP concentrations. These results indicated that DP exposure changed both the structure and metabolic function of the gut microbiota, suggesting more attention should be concentrated on the health effects of DP exposure, especially at higher doses.

Interleukin-17A deficient mice microbiota induced regulatory T cells and suppressed experimental autoimmune encephalomyelitis (EAE) in WT HLA-DR3 transgenic mice

Abstract Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system, and among all the genes associated with MS, HLA class II genes have the highest relative risk. Although IL-17A is thought to be a major cytokine in the pathogenesis of MS, the exact role of IL-17A in the MS is still poorly understood. Specifically, it is unclear whether IL-17A is required for disease initiation or disease severity or in both. Therefore, in the present study, utilizing HLA-DR3 transgenic mice lacking IL-17A (HLA-DR3.IL-17A−/−), we investigated the importance of IL-17A in disease development and progression in experimental autoimmune encephalomnyelitis (EAE) an animal model of MS. We observed that HLA-DR3.IL-17A−/− mice had a higher frequency of CD4+CD25+FoxP3+ regulatory T cells (Treg)s and developed milder EAE compared to IL-17 sufficient HLA-DR3 mice. Further characterization of mechanism identified a novel role of IL-17A in regulating the disease progression through modulation of immunoregulatory responses. We also identified an important role of gut microbiota in IL-17A dependent disease regulation specifically depletion of gut bacteria with ability to promote Treg population in IL-17A sufficient HLA-DR3 mice. Fecal transplantation of HLA.DR3 mice with HLA-DR3. IL17A−/− showed milder EAE and an increase in Treg cells in HLA-DR3 mice confirming a role of gut microbiota in shaping Treg repertoire and function. Additionally, we observed higher frequency of metabolic pathway involved with Treg promoting short chain fatty acid (SCFA) metabolism in HLA-DR3.IL17A−/− mice. Thus our study shows a novel role of IL-17A in immune homeostasis and inflammation by regulating levels of Tregs through modulation of gut microbiota.

Microbiota‐derived butyrate is an endogenous inhibitor of HIF prolyl‐hydroxylases

The diverse population of microbial species present in the human intestines, collectively termed the gut microbiota, is an essential component of human health. Microbial supply of fermentation-derived short-chain fatty acids (SCFAs), particularly butyrate, is a well-established component to gut homeostasis and disease resistance. Reaching millimolar luminal concentrations in the colon, butyrate is sequestered and utilized as the favored energy source for intestinal epithelial cells. Beyond energy provision, butyrate broadly regulates gene expression as a histone deacetylase inhibitor and modulates the intestinal environment via signaling through SCFA-specific G-protein coupled receptors. Additionally, increasing oxygen utilization due to SCFA metabolism has been shown to stabilize hypoxia-inducible factor (HIF), a transcription factor that broadly functions as the master regulator of oxygen homeostasis but also specifically maintains intestinal homeostasis and is essential to intestinal barrier function. Under normoxic conditions, HIF is degraded in a hydroxylation-dependent manner mediated by one of three HIF prolyl-hydroxylases (PHDs). When oxygen is limiting, PHDs are inhibited and HIF is stabilized. Given the low O2 conditions of the intestinal microenvironment, it is of interest whether butyrate could more specifically influence HIF. We show that the microbiota-derived butyrate directly binds and inhibits PHD2 to stabilize HIF. Using cultured epithelia and molecular approaches, we found that butyrate treatment stabilized HIF in vitro independent of oxygen metabolism. Utilizing recombinant PHD protein, we identified butyrate as a unique inhibitor of PHD relative to other SCFAs. We also found that butyrate delivered to the colon of mice stabilizes HIF in a specific manner. Our results suggest that the co-evolution of mammals and commensal bacteria have selected for butyrate to impact a crucial gene regulation pathway that could be extended to beyond the intestinal mucosa. PHDs are a major target for drug development, as HIF regulates numerous genes involved in erythropoiesis, angiogenesis, energy metabolism, ischemia, and inflammation. Small-molecule inhibitors of PHDs have been developed in hopes of treating a variety of diseases not limited to chronic kidney disease and inflammatory bowel diseases. As an endogenous, well-tolerated small-molecule metabolite, butyrate holds far-reaching therapeutic potential as a HIF stabilizing agent.

1 H NMR-based metabolomics of paired esophageal tumor tissues and serum samples identifies specific serum biomarkers for esophageal cancer.

Serum metabolites of healthy controls and esophageal cancer (EC) patients have previously been compared to predict cancer-specific profiles. However, the association between metabolic alterations in serum samples and esophageal tissues in EC patients remains unclear. Here, we analyzed 50 pairs of EC tissues and distant noncancerous tissues, together with patient-matched serum samples, using 1 H NMR spectroscopy and pattern recognition algorithms. EC patients could be differentiated from the controls based on the metabolic profiles at tissue and serum levels. Some overlapping discriminatory metabolites, including valine, alanine, glucose, acetate, citrate, succinate and glutamate, were identified in both matrices. These results suggested deregulation of metabolic pathways, and potentially revealed the links between EC and several metabolic pathways, such as the tricarboxylic acid cycle, glutaminolysis, short-chain fatty acid metabolism, lipometabolism and pyruvate metabolism. Perturbation of the pyruvate metabolism was most strongly associated with EC progression. Consequently, an optimal serum metabolite biomarker panel comprising acetate and pyruvate was developed, as these two metabolites are involved in pyruvate metabolism, and changes in their serum levels were significantly correlated with alterations in the levels of some other esophageal tissue metabolites. In comparison with individual biomarkers, this panel exhibited better diagnostic efficiency for EC, with an AUC of 0.948 in the test set, and a good predictive ability of 82.5% in the validation set. Analysis of key genes related to pyruvate metabolism in EC patients revealed patterns corresponding to the changes in serum pyruvate and acetate levels. These correlation analyses demonstrate that there were distinct metabolic characteristics and pathway aberrations in the esophageal tumor tissue and in the serum. Changes in the serum metabolic signatures could reflect the alterations in the esophageal tumor profile, thereby emphasizing the importance of distinct serum metabolic profiles as potential noninvasive biomarkers for EC.

The effects of myeloablative or non-myeloablative total body irradiations on intestinal tract in mice.

Acute radiation injury caused by high-dose radiation exposure severely impedes the application of radiotherapy in cancer management. To deeply understand the side effects of radiation on intestinal tract, an irradiation murine model was applied and evaluated. C57BL/6 mice were given 4 Gy non-myeloablative irradiation, 8 Gy myeloablative irradiation and non-irradiation (control), respectively. Results demonstrated that the 8 Gy myeloablative irradiations significantly damaged the gut barrier along with decreasing MECA32 and ZO-1. However, a slight increase in MECA32 and ZO-1 was detected in the 4 Gy non-myeloablative irradiations treatment from day 5 to day 10. Further, the irradiations affected the expression of P38 and JNK mitogen-activated protein kinase (MAPK) but not ERK1/2 MAPK signal pathway. Moreover, irradiation had adverse effects on hematopoietic system, altered the numbers and percentages of intestinal inflammatory cells. The IL-17/AhR had big increase in the gut of 4 Gy irradiation mice at day 10 compared with other groups. Both 8 Gy myeloablative and 4 Gy non-myeloablative irradiation disturbed the levels of short-chain fatty acids (SCFAs) in intestine. Meanwhile, high dosage of irradiation decreased the intestinal bacterial diversity and altered the community composition. Importantly, the fatty acids generating bacteria Bacteroidaceae and Ruminococcaceae played key roles in community distribution and SCFAs metabolism after irradiation. Collectively, the irradiation induced gut barrier damage with dosages dependent that led to the decreased p38 MAPK and increased JNK MAPK, unbalanced the mononuclear cells (MNCs) of gut, disturbed intestinal bacterial community and SCFAs level.

Intestinal Microbiota and Perspectives of the Use of Meta-Analysis for Comparison of Ulcerative Colitis Studies.

Meta-analysis is a statistical process summarizing comparable data from a number of scientific papers. The use of meta-analysis in microbiology allows decision-making that has an impact on public health policy. It can happen that the primary researches come to different conclusions, although these are targeted with the same research question. It is, therefore, inevitable to have the means to systematically evaluate information and compare research results. Ulcerative colitis together with Crohn’s disease are among the two main inflammatory bowel diseases. This chronic disease of the gastrointestinal tract, with an as yet unclear etiology, is presented by an uncontrolled inflammatory immune response in genetically predisposed individuals to as yet undefined environmental factors in interaction with the intestinal microbiota itself. In patients with ulcerative colitis (UC), changes in the composition and relative abundance of microorganisms could be observed. Sulfate-reducing bacteria (SRB), which commonly occur in the large intestine as part of the commensal microbiota of animals and humans involved in the pathogenesis of the disease, have been shown to occur. SRB are anaerobic organisms affecting short-chain fatty acid metabolism. This work outlines the perspectives of the use of meta-analysis for UC and changes in the representation of intestinal organisms in these patients.

Metabolic Phenotypes as Potential Biomarkers for Linking Gut Microbiome With Inflammatory Bowel Diseases.

The gut microbiome is of utmost importance to human health. While a healthy microbiome can be represented by a variety of structures, its functional capacity appears to be more important. Gene content of the community can be assessed by “shotgun” metagenomics, but this approach is still too expensive. High-throughput amplicon-based surveys are a method of choice for large-scale surveys of links between microbiome, diseases, and diet, but the algorithms for predicting functional composition need to be improved to achieve good precision. Here we show how feature engineering based on microbial phenotypes, an advanced method for functional prediction from 16S rRNA sequencing data, improves identification of alterations of the gut microbiome linked to the disease. We processed a large collection of published gut microbial datasets of inflammatory bowel disease (IBD) patients to derive their community phenotype indices (CPI)—high-precision semiquantitative profiles aggregating metabolic potential of the community members based on genome-wide metabolic reconstructions. The list of selected metabolic functions included metabolism of short-chain fatty acids, vitamins, and carbohydrates. The machine-learning approach based on microbial phenotypes allows us to distinguish the microbiome profiles of healthy controls from patients with Crohn's disease and from ones with ulcerative colitis. The classifiers were comparable in quality to conventional taxonomy-based classifiers but provided new findings giving insights into possible mechanisms of pathogenesis. Feature-wise partial dependence plot (PDP) analysis of contribution to the classification result revealed a diversity of patterns. These observations suggest a constructive basis for defining functional homeostasis of the healthy human gut microbiome. The developed features are promising interpretable candidate biomarkers for assessing microbiome contribution to disease risk for the purposes of personalized medicine and clinical trials.

Methane and fatty acid metabolism pathways are predictive of Low-FODMAP diet efficacy for patients with irritable bowel syndrome

Identification of microbiota-based biomarkers as predictors of low-FODMAP diet response and design of a diet recommendation strategy for IBS patients. We created a compendium of gut microbiome and disease severity data before and after a low-FODMAP diet treatment from published studies followed by unified data processing, statistical analysis and predictive modeling. We employed data-driven methods that solely rely on the compendium data, as well as hypothesis-driven methods that focus on methane and short chain fatty acid (SCFA) metabolism pathways that were implicated in the disease etiology. The patient's response to a low-FODMAP diet was predictable using their pre-diet fecal samples with F1 accuracy scores of 0.750 and 0.875 achieved through data-driven and hypothesis-driven predictors, respectively. The fecal microbiome of patients with high response had higher abundance of methane and SCFA metabolism pathways compared to patients with no response (p-values<6×10-3). The genera Ruminococcus 1, Ruminococcaceae UCG-002 and Anaerostipes can be used as predictive biomarkers of diet response. Furthermore, the low-FODMAP diet followers were identifiable given their microbiome data (F1-score of 0.656). Our integrated data analysis results argue that there are two types of patients, those with high colonic methane and SCFA production, who will respond well on a low-FODMAP diet, and all others, who would benefit a dietary supplementation containing butyrate and propionate, as well as probiotics with SCFA-producing bacteria, such as lactobacillus. This work demonstrates how data integration can lead to novel discoveries and paves the way towards personalized diet recommendations for IBS.

Study on fecal fermentation characteristics of aloe polysaccharides in vitro and their predictive modeling

Aloe polysaccharides (APs) are well-known plant polysaccharides, but little is known about their digestion and fermentation characteristics in vitro. In this study, the molecular weight of APs had no significant changes after gastric and intestinal digestion. During the fecal fermentation, the content of volatiles and pH value decreased continuously, while the short-chain fatty acids (SCFAs) concentration increased significantly. Additionally, the abundance of the microbiota associated with the metabolism of SCFAs was increased, including Prevotella, Catenibacterium, Lachnospiraceae, and Coprococcus, while the harmful microbiota was decreased, like Escherichia-Shigella, and Veillonella. Moreover, bioinformatics analysis indicated that APs boosted fructose and mannose metabolism, and the gene expressions of enzymes, containing mannose-6-phosphate isomerase [EC:5.3.1.8]. Structural equation modeling also highlighted that SCFAs-producing microbiota were primary degraders of APs, suggesting APs may facilitate the manufacture of functional foods with the purpose of maintaining intestinal health.

Effect of dietary folate level on organ weight, digesta pH, short-chain fatty acid concentration, and intestinal microbiota of weaned piglets.

Folate is increasingly thought to promote gastrointestinal health and regulate the diversity of gut microbiota to alleviate weaning stress in piglets. The present study was conducted to investigate the effects of folate on organ weight, digesta pH, short-chain fatty acids (SCFAs) concentration, and intestinal microbiota in weaned piglets. A total of 28 piglets (6.73 ± 0.62 kg) were allocated to four dietary treatments consisting of a control group, 3, 9, and 18 mg/kg of folate supplementation in a 14-d feeding trial. The results showed that piglets fed with 9 and 18 mg/kg of folate supplementation had greater (P < 0.05) average liver and spleen weight than the control group. Folate supplementation (9 and 18 mg/kg) can significantly increase (P < 0.05) the stomach pH and tend (P < 0.10) to decrease the cecum pH. Folate treatment (9 and 18 mg/kg) had a positive effect on the metabolism of SCFAs in piglets, in particular, compared with the control group, and the content of acetic acid (AA) and valeric acid was markedly increased (P < 0.05) in the cecum and colon, respectively. Moreover, isobutyric acid, butyric acid, and isovaleric acid were tended (P < 0.10) to increase in the colon. Cecum contents samples were used to determine bacterial community diversity by 16S rRNA gene amplicon sequencing. At the genus level, in the cecum, there was a higher (P < 0.05) relative abundance of Lactobacillus reuteri, Lactobacillus salivarius, and Lactobacillus mucosae in the 9 mg/kg folate supplementation group. The functional pathways analysis predicted that folate may modify nutrient metabolism by changing the gut microbiota function of weaned piglets. Furthermore, the data showed that Lactobacillus was positively correlated with AA in the cecum. Overall, these findings suggested that folate treatment could increase the organ weight and the stomach pH of weaned piglets and had beneficial effects on gut health, which might be attributed to the alteration in intestinal microbiota induced by folate and the interaction of the intestinal microbiota with SCFAs.

Bifidobacterium animalis F1-7 in combination with konjac glucomannan improves constipation in mice via humoral transport.

Probiotics and natural products can promote humoral transport and effectively relieve intestinal motility. This study investigated the effects of probiotics in combination with konjac glucomannan (KGM) and an aqueous extract of Prunus persica on constipation. The growth promotion effect of these natural products on probiotics was investigated using co-culture in vitro. The combined effect of probiotics and natural products on constipation was observed in mice. The tryptophan, tryptamine and short-chain fatty acid levels were determined using enzyme-linked immunosorbent assay, reverse-phase high-performance liquid chromatography, and gas chromatography. The key genes and proteins involved in humoral transport were identified using real-time polymerase chain reaction, western blotting and fluorescence immunoassay. KGM promoted the growth of Bifidobacterium animalis F1-7 in vitro, and a mixture of KGM and B. animalis F1-7 effectively promoted defaecation in mice, increased the faecal water content, shortened the defaecation time and improved the gastrointestinal transit rate. In mice, the KGM + F1-7 mixture reduced the tryptophan level and increased the levels of tryptamine, acetic acid, propionic acid, butyric acid and valeric acid. In addition, the KGM + F1-7 mixture effectively increased the mRNA level of 5-HT4-G-protein-coupled receptors (5-HT4GPCR)/mucins-2 (MUC-2) and reduced the level of aquaporins (AQP3); furthermore, it upregulated the protein level of 5-HT4GPCR/MUC-2 and downregulated the protein level of AQP3. These findings indicated that the KGM + F1-7 mixture effectively improved intestinal motility and alleviated constipation through humoral transport-related pathways.

Targeted metabolomic analysis of seven short-chain fatty acids in feces of rats with spleen-deficiency syndrome after administering raw and bran-fried atractylodis rhizoma by gas chromatography-mass spectrometer

Background: For treating spleen-deficiency syndrome (SDS), atractylodis rhizoma (AR) is usually treated with bran, which is measured to enhance efficacy. Newly, we found that bran-fried AR (BFA) had benefits over raw AR in refining gut flora. However, the change about metabolism of gut flora caused by raw and BFA remains unclear. Aim: The aim of this study was to compare the difference between raw and BFA acting on short-chain fatty acid (SCFA) metabolism in SDS rats, a metabolic pathway comprising gut flora. Materials and Methods: The model of SDS rats was recognized and then given raw and BFA by gavage. The serum was collected for the determination of motilin (MTL), gastrin (GAS), trypsin (TRY), and amylase (AMS) by enzyme-linked immunosorbent assay. The feces were collected for the determination of 7 SCFAs under selective ion monitoring mode by gas chromatography-mass spectrometer. Results: Raw and BFA can upsurge the levels of MTL, GAS, TRY, and AMS in the serum of SDS rats, diminution the levels of acetic acid and propionic acid, and rise the level of hexanoic acid in the feces of SDS rats, and BFA showed noteworthy activity than raw AR. Conclusion: Raw and BFA can improve the acetic acid, propionic acid, and hexanoic acid metabolism in SDS rats, and BFA was more potent than raw AR.

Nutritional combinatorial impact on the gut microbiota and plasma short-chain fatty acids levels in the prevention of mammary cancer in Her2/neu estrogen receptor-negative transgenic mice.

Breast cancer is the second leading cause of cancer-related mortality in women. Various nutritional compounds possess anti-carcinogenic properties which may be mediated through their effects on the gut microbiota and its production of short-chain fatty acids (SCFAs) for the prevention of breast cancer. We evaluated the impact of broccoli sprouts (BSp), green tea polyphenols (GTPs) and their combination on the gut microbiota and SCFAs metabolism from the microbiota in Her2/neu transgenic mice that spontaneously develop estrogen receptor-negative [ER(-)] mammary tumors. The mice were grouped based on the dietary treatment: control, BSp, GTPs or their combination from beginning in early life (BE) or life-long from conception (LC). We found that the combination group showed the strongest inhibiting effect on tumor growth volume and a significant increase in tumor latency. BSp treatment was integrally more efficacious than the GTPs group when compared to the control group. There was similar clustering of microbiota of BSp-fed mice with combination-fed mice, and GTPs-fed mice with control-fed mice at pre-tumor in the BE group and at pre-tumor and post-tumor in the LC group. The mice on all dietary treatment groups incurred a significant increase of Adlercreutzia, Lactobacillus genus and Lachnospiraceae, S24-7 family in the both BE and LC groups. We found no change in SCFAs levels in the plasma of BSp-fed, GTPs-fed and combination-fed mice of the BE group. Marked changes were observed in the mice of the LC group consisting of significant increases in propionate and isobutyrate in GTPs-fed and combination-fed mice. These studies indicate that nutrients such as BSp and GTPs differentially affect the gut microbial composition in both the BE and LC groups and the key metabolites (SCFAs) levels in the LC group. The findings also suggest that temporal factors related to different time windows of consumption during the life-span can have a promising influence on the gut microbial composition, SCFAs profiles and ER(-) breast cancer prevention.

Konjac glucomannan with probiotics acts as a combination laxative to relieve constipation in mice by increasing short-chain fatty acid metabolism and 5-hydroxytryptamine hormone release

ObjectivesVarious probiotics and natural products can help to relieve constipation. This study aimed to explore the constipation-relieving effects and potential mechanism of a combination laxative of konjac glucomannan and probiotics. MethodsThis study evaluated the gastrointestinal-tract viability of probiotics in vitro. A constipation model was constructed in BALB/c mice, and the efficacies of the combinations verified in terms of their bowel movement–promoting effects, including the first black-stool defecation time and gastrointestinal transit rates of mice. Colonization by the probiotics was determined by quantitative real-time polymerase chain reaction. Hematoxylin-eosin staining, gas chromatography, enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction, and Western blot were also used for analysis. ResultsLactobacillus paracasei X11 (X11) and L. casei YRL577 (YRL577) had outstanding gastrointestinal-tract viability. Konjac glucomannan (KGM) + X11, Prunus persica + X11, and Prunus persica + YRL577 significantly relieved constipation. In addition, KGM promoted the colonization of X11. Meanwhile, KGM + X11 effectively promoted the metabolism of short-chain fatty acids in mice better than other combinations, and the 5-hydroxytryptamine (5-HT) content in the KGM + X11 group was the highest among all the groups. Therefore, KGM + X11 was selected for further research. The combination laxative promoted the secretion of 5-HT, up-regulated mRNA and protein levels of 5-HT receptor 4 and serotonin transporter via the 5-HT pathway, and effectively relieved constipation. ConclusionsThe combination laxative konjac glucomannan–probiotic (KGM + X11) promoted defecation in constipated mice, possibly by increasing short-chain fatty acid metabolism and 5-HT hormone release.

Dietary Inulin Supplementation Modulates Short-Chain Fatty Acid Levels and Cecum Microbiota Composition and Function in Chickens Infected With Salmonella.

The current study investigated the effects of inulin on the gut microbiota, microbiome functions, and short-chain fatty acids (SCFAs) levels in specific pathogen-free (SPF) chickens infected with Salmonella enteritidis (SE). SPF Arbor Acres chickens (n = 240, 1-day-old) were divided into four groups: a control group (CON) fed a basal diet without inulin supplementation or SE infection, and three groups fed a basal diet supplemented with inulin 0, 0.5, and 1% (SE, 0.5%InSE, 1%InSE, respectively) up to 28-days-old, followed by SE challenge at 28 days of age. Cecal SCFA contents and microbiome composition and function were analyzed at 1-day post-infection. The results showed that SE infection significantly decreased cecal butyrate concentrations compared with the CON group (p < 0.05), while inulin supplementation reversed these changes compared with the SE group (p < 0.05). Inulin supplementation at 1% significantly increased the abundances of Lactobacillus and Streptococcus, and significantly decreased the abundances of Subdoligranulum and Sellimonas compared with the SE group (p < 0.05). The functional profiles of microbial communities based on metagenomic sequencing analysis showed that SE infection significantly increased the abundances of pathways related to carbohydrate metabolism, amino acid metabolism, energy metabolism, metabolism of cofactors and vitamins, and glycan biosynthesis and metabolism (p < 0.05), and significantly decreased the abundances of pathways related to nucleotide metabolism, translation, and replication and repair compared with the CON group (p < 0.05), and these effects were reversed by inulin supplementation (0.5 and 1%) (p < 0.05). In conclusion, inulin modulated the dysbiosis induced by SE infection via affecting SCFA metabolism and microbial functional profiles.