ABSTRACT
Grapes provide a rich source of polyphenols and fibers. This study aimed to evaluate the effect of the daily consumption of 46 g of whole grape powder, providing the equivalent of two servings of California table grapes, on the gut microbiome and cholesterol/bile acid metabolism in healthy adults. This study included a 4-week standardization to a low-polyphenol diet, followed by 4 weeks of 46 g of grape powder consumption while continuing the low-polyphenol diet. Compared to the baseline, 4 weeks of grape powder consumption significantly increased the alpha diversity index of the gut microbiome. There was a trend of increasing Verrucomicrobia (p = 0.052) at the phylum level, and a significant increase in Akkermansia was noted. In addition, there was an increase in Flavonifractor and Lachnospiraceae_UCG-010, but a decrease in Bifidobacterium and Dialister at the genus level. Grape powder consumption significantly decreased the total cholesterol by 6.1% and HDL cholesterol by 7.6%. There was also a trend of decreasing LDL cholesterol by 5.9%, and decreasing total bile acid by 40.9%. Blood triglyceride levels and body composition were not changed by grape powder consumption. In conclusion, grape powder consumption significantly modified the gut microbiome and cholesterol/bile acid metabolism.
Subject(s)
Bile Acids and Salts/metabolism , Cholesterol/metabolism , Gastrointestinal Microbiome/drug effects , Plant Extracts/administration & dosage , Vitis/chemistry , Adult , Akkermansia/drug effects , Bifidobacterium/drug effects , Cholesterol/blood , Female , Healthy Volunteers , Humans , Male , Middle Aged , Pilot Projects , Polyphenols/metabolism , Powders , Triglycerides/blood , Verrucomicrobia/drug effects , Young AdultABSTRACT
The allicin diallyldisulfid-S-oxide, a major garlic organosulfur compound (OSC) in crushed garlic (Allium sativum L.), possesses antibacterial effects, and influences gut bacteria. In this study, we made allicin-free garlic (AFG) extract and investigated its effects on gut microbiome. C57BL/6N male mice were randomly divided into 6 groups and fed normal diet (ND) and high-fat diet (HFD) supplemented with or without AFG in concentrations of 1% and 5% for 11 weeks. The genomic DNAs of feces were used to identify the gut microbiome by sequencing 16S rRNA genes. The results revealed that the ratio of p-Firmicutes to p-Bacteroidetes increased by aging and HFD was reduced by AFG. In particular, the f-Lachnospiraceae, g-Akkermansia, and g-Lactobacillus decreased by aging and HFD was enhanced by AFG. The g-Dorea increased by aging and HFD decreased by AFG. In addition, the ratio of glutamic-pyruvic transaminase to glutamic-oxaloacetic transaminase (GPT/GOT) in serum was significantly increased in the HFD group and decreased by AFG. In summary, our data demonstrated that dietary intervention with AFG is a potential way to balance the gut microbiome disturbed by a high-fat diet.
Subject(s)
Anti-Bacterial Agents/pharmacology , Dietary Supplements , Garlic/chemistry , Gastrointestinal Microbiome/drug effects , Plant Extracts/pharmacology , Alanine Transaminase/blood , Animals , Aspartate Aminotransferases/blood , Bacteroidetes/drug effects , Bacteroidetes/isolation & purification , Diet, High-Fat , Disulfides , Firmicutes/drug effects , Firmicutes/isolation & purification , Garlic/genetics , Male , Mice , Mice, Inbred C57BL , Sulfinic Acids/analysis , Verrucomicrobia/drug effects , Verrucomicrobia/isolation & purificationABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Hua-Feng-Dan (HFD) is a traditional Chinese medicine used for neurological disorders. HFD contains cinnabar (HgS) and realgar (As4S4). The ethnopharmacological basis of cinnabar and realgar in HFD is not known. AIM OF THE STUDY: To address the role of cinnabar and realgar in HFD-produced neuroprotection against neurodegenerative diseases and disturbance of gut microbiota. MATERIALS AND METHODS: Lipopolysaccharide (LPS) plus rotenone (ROT)-elicited rat dopaminergic (DA) neuronal damage loss was performed as a Parkinson's disease animal model. Rats were given a single injection of LPS. Four months later, rats were challenged with the threshold dose of ROT. The clinical dose of HFD was administered via feed, starting from ROT administration for 46 days. Behavioral dysfunction was detected by rotarod and Y-maze tests. DA neuron loss and microglial activation were assessed via immunohistochemical staining and western bolt analysis. The colon content was collected to extract bacterial DNA followed by real-time PCR analysis with 16S rRNA primers. RESULTS: LPS plus ROT induced neurotoxicity, as evidenced by DA neuron loss in substantia nigra, impaired behavioral functions and increased microglial activation. HFD-original (containing 10% cinnabar and 10% realgar) rescued loss of DA neurons, improved behavioral dysfunction and attenuated microglial activation. Compared with HFD-original, HFD-reduced (3% cinnabar and 3% realgar) was also effective, but to be a less extent, while HFD-removed (without cinnabar and realgar) was ineffective. In analysis of gut microbiome, the increased Verrucomicrobiaceae and Lactobacteriaceae, and the decreased Enterobacteeriaceae by LPS plus ROT were ameliorated by HFD-original, and to be the less extent by HFD-reduced. CONCLUSION: Cinnabar and realgar are active ingredients in HFD to exert beneficial effects in a neurodegenerative model and gut microbiota.
Subject(s)
Arsenicals/pharmacology , Drugs, Chinese Herbal/pharmacology , Gastrointestinal Microbiome/drug effects , Mercury Compounds/pharmacology , Neuroprotective Agents/pharmacology , Neurotoxicity Syndromes/drug therapy , Sulfides/pharmacology , Animals , Arsenicals/chemistry , Arsenicals/therapeutic use , DNA, Bacterial/isolation & purification , Disease Models, Animal , Dopaminergic Neurons/drug effects , Dopaminergic Neurons/pathology , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/therapeutic use , Enterobacteriaceae/drug effects , Enterobacteriaceae/genetics , Enterobacteriaceae/isolation & purification , Ethnopharmacology , Gastrointestinal Microbiome/genetics , Gastrointestinal Microbiome/immunology , Humans , Inflammation Mediators/metabolism , Lactobacillaceae/drug effects , Lactobacillaceae/genetics , Lactobacillaceae/isolation & purification , Lipopolysaccharides/toxicity , Male , Mercury Compounds/chemistry , Mercury Compounds/therapeutic use , Microglia/drug effects , Microglia/immunology , Microglia/pathology , Nerve Degeneration , Neuroprotective Agents/chemistry , Neuroprotective Agents/therapeutic use , Neurotoxicity Syndromes/etiology , Neurotoxicity Syndromes/immunology , Neurotoxicity Syndromes/pathology , RNA, Ribosomal, 16S/genetics , Rats , Rotenone/toxicity , Sulfides/chemistry , Sulfides/therapeutic use , Verrucomicrobia/drug effects , Verrucomicrobia/genetics , Verrucomicrobia/isolation & purificationABSTRACT
Estrogen decline during menopause is associated with altered metabolism, weight gain and increased risk of cardiometabolic diseases. The gut microbiota also plays a role in the development of cardiometabolic dysfunction and is also subject to changes associated with age-related hormone changes. Phytoestrogens are plant-based estrogen mimics that have gained popularity as dietary supplements for the treatment or prevention of menopause-related symptoms. These compounds have the potential to both modulate and be metabolized by the gut microbiota. Hops (Humulus lupulus L.) contain potent phytoestrogen precursors, which rely on microbial biotransformation in the gut to estrogenic forms. We supplemented ovariectomized (OVX) or sham-operated (SHAM) C57BL/6 mice, with oral estradiol (E2), a flavonoid-rich extract from hops, or a placebo carrier oil, to observe effects on adiposity, inflammation, and gut bacteria composition. Hops extract (HE) and E2 protected against increased visceral adiposity and liver triglyceride accumulation in OVX animals. Surprisingly, we found no evidence of OVX having a significant impact on the overall gut bacterial community structure. We did find differences in the abundance of Akkermansia muciniphila, which was lower with HE treatment in the SHAM group relative to OVX E2 treatment and to placebo in the SHAM group.
Subject(s)
Estrogens/pharmacology , Flavonoids/pharmacology , Gastrointestinal Microbiome , Humulus/chemistry , Plant Extracts/pharmacology , Adiposity/drug effects , Akkermansia , Animals , Dietary Supplements/microbiology , Estradiol/pharmacology , Female , Flavanones , Mice , Mice, Inbred C57BL , Models, Animal , Ovariectomy , Phytoestrogens/pharmacology , Triglycerides/metabolism , Verrucomicrobia/drug effects , Weight Gain/drug effectsSubject(s)
Fruit , Gastrointestinal Microbiome/drug effects , Intestines/drug effects , Lactobacillus/drug effects , Non-alcoholic Fatty Liver Disease/drug therapy , Phytotherapy/methods , Plant Extracts/therapeutic use , Plant Leaves , Rubus , Verrucomicrobia/drug effects , Animals , Gastrointestinal Microbiome/genetics , Intestines/microbiology , Intestines/pathology , Liver/drug effects , Liver/pathology , Male , Non-alcoholic Fatty Liver Disease/pathology , Rats , Rats, Sprague-Dawley , Real-Time Polymerase Chain ReactionABSTRACT
SCOPE: The prevalence of obesity and related disorders has vastly increased throughout the world and prevention of such circumstances thus represents a major challenge. Here, it has been shown that one protein-bound ß-glucan (PBG) from the edible mushroom Coriolus versicolor can be a potent anti-obesity component. METHODS AND RESULTS: PBG can reduce obesity and metabolic inflammation in mice fed with a high-fat diet (HFD). Gut microbiota analysis reveals that PBG markedly increases the abundance of Akkermansia muciniphila, although it does not rescue HFD-induced change in the Firmicutes to Bacteroidetes ratio. It appears that PBG alters host physiology and creates an intestinal microenvironment favorable for A. muciniphila colonization. Fecal transplants from PBG-treated animals in part reduce obesity in recipient HFD-fed mice. Further, PBG is shown to upregulate expression of a set of genes related to host metabolism in microbiota-depleted mice. CONCLUSION: The data highlight that PBG may exert its anti-obesity effects through a mirobiota-dependent (richness of specific microbiota) and -independent (modulation of host metabolism) manner. The fact that C. versicolor PBGs are approved oral immune boosters in cancers and chronic hepatitis with well-established safety profiles may accelerate PBG as a novel use for obesity treatment.
Subject(s)
Agaricales/chemistry , Anti-Obesity Agents/pharmacology , Obesity/prevention & control , beta-Glucans/chemistry , beta-Glucans/pharmacology , Animals , Anti-Obesity Agents/chemistry , Cytokines/blood , Diet, High-Fat/adverse effects , Drug Evaluation, Preclinical/methods , Fecal Microbiota Transplantation , Female , Fungal Proteins/chemistry , Fungal Proteins/pharmacology , Gastrointestinal Microbiome/drug effects , Gene Expression Regulation/drug effects , Inflammation/drug therapy , Inflammation/metabolism , Mice, Inbred C57BL , Obesity/etiology , Obesity/therapy , Verrucomicrobia/drug effectsABSTRACT
Recently, accumulating evidence has suggested that Enteromorpha clathrata polysaccharide (ECP) could contribute to the treatment of diseases. However, as a promising candidate for marine drug development, although ECP has been extensively studied, less consideration has been given to exploring its effect on gut microbiota. In this light, given the critical role of gut microbiota in health and disease, we investigated here the effect of ECP on gut microbiota using 16S rRNA high-throughput sequencing. As revealed by bioinformatic analyses, ECP considerably changed the structure of the gut microbiota and significantly promoted the growth of probiotic bacteria in C57BL/6J mice. However, interestingly, ECP exerted different effects on male and female microbiota. In females, ECP increased the abundances of Bifidobacterium spp. and Akkermansia muciniphila, a next-generation probiotic bacterium, whereas in males, ECP increased the population of Lactobacillus spp. Moreover, by shaping a more balanced structure of the microbiota, ECP remarkably reduced the antigen load from the gut in females. Altogether, our study demonstrates for the first time a prebiotic effect of ECP on gut microbiota and forms the basis for the development of ECP as a novel gut microbiota modulator for health promotion and disease management.
Subject(s)
Aquatic Organisms/metabolism , Dysbiosis/drug therapy , Gastrointestinal Microbiome/drug effects , Polysaccharides/pharmacology , Ulva/metabolism , Acute-Phase Proteins/immunology , Administration, Oral , Animals , Bifidobacterium/drug effects , Bifidobacterium/isolation & purification , Carrier Proteins/blood , Carrier Proteins/immunology , Computational Biology , Dietary Supplements , Disease Models, Animal , Dysbiosis/blood , Dysbiosis/immunology , Female , Humans , Lactobacillus/drug effects , Lactobacillus/isolation & purification , Male , Membrane Glycoproteins/blood , Membrane Glycoproteins/immunology , Mice , Mice, Inbred C57BL , Polysaccharides/isolation & purification , Polysaccharides/therapeutic use , Specific Pathogen-Free Organisms , Verrucomicrobia/drug effects , Verrucomicrobia/isolation & purificationABSTRACT
BACKGROUND AND AIMS: Gut microbiota plays a major role in metabolic disorders. Berberine is used to treat obesity, diabetes and atherosclerosis. The mechanism underlying the role of berberine in modulating metabolic disorders is not fully clear because berberine has poor oral bioavailability. Thus, we evaluated whether the antiatherosclerotic effect of berberine is related to alterations in gut microbial structure and if so, whether specific bacterial taxa contribute to the beneficial effects of berberine. METHODS: Apoe-/- mice were fed either a normal-chow diet or a high-fat diet (HFD). Berberine was administered to mice in drinking water (0.5 g/L) for 14 weeks. Gut microbiota profiles were established by high throughput sequencing of the V3-V4 region of the bacterial 16S ribosomal RNA gene. The effects of berberine on metabolic endotoxemia, tissue inflammation and gut barrier integrity were also investigated. RESULTS: Berberine treatment significantly reduced atherosclerosis in HFD-fed mice. Akkermansia spp. abundance was markedly increased in HFD-fed mice treated with berberine. Moreover, berberine decreased HFD-induced metabolic endotoxemia and lowered arterial and intestinal expression of proinflammatory cytokines and chemokines. Berberine treatment increased intestinal expression of tight junction proteins and the thickness of the colonic mucus layer, which are related to restoration of gut barrier integrity in HFD-fed mice. CONCLUSIONS: Modulation of gut microbiota, specifically an increase in the abundance of Akkermansia, may contribute to the antiatherosclerotic and metabolic protective effects of berberine, which is poorly absorbed orally. Our findings therefore support the therapeutic value of gut microbiota manipulation in treating atherosclerosis.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Aorta/drug effects , Aortic Diseases/prevention & control , Atherosclerosis/prevention & control , Berberine/pharmacology , Diet, High-Fat , Gastrointestinal Microbiome/drug effects , Intestinal Mucosa/drug effects , Verrucomicrobia/drug effects , Animals , Aorta/metabolism , Aorta/pathology , Aortic Diseases/genetics , Aortic Diseases/metabolism , Aortic Diseases/microbiology , Atherosclerosis/genetics , Atherosclerosis/metabolism , Atherosclerosis/microbiology , Cytokines/metabolism , Disease Models, Animal , Female , Inflammation Mediators/metabolism , Intestinal Mucosa/metabolism , Intestinal Mucosa/microbiology , Mice, Inbred C57BL , Mice, Knockout, ApoE , Plaque, Atherosclerotic , Tight Junction Proteins/metabolism , Verrucomicrobia/growth & development , Verrucomicrobia/metabolismABSTRACT
The gut and its bacterial colonizers are now well characterized as key players in whole-body metabolism, opening new avenues of research and generating great expectation for new treatments against obesity and its cardiometabolic complications. As diet is the main environmental factor affecting the gut microbiota, it has been suggested that fruits and vegetables, whose consumption is strongly associated with a healthy lifestyle, may carry phytochemicals that could help maintain intestinal homeostasis and metabolic health. We recently demonstrated that oral administration of a cranberry extract rich in polyphenols prevented diet-induced obesity and several detrimental features of the metabolic syndrome in association with a remarkable increase in the abundance of the mucin-degrading bacterium Akkermansia in the gut microbiota of mice. This addendum provides an extended discussion in light of recent discoveries suggesting a mechanistic link between polyphenols and Akkermansia, also contemplating how this unique microorganism may be exploited to fight the metabolic syndrome.
Subject(s)
Metabolic Syndrome/drug therapy , Plant Extracts/administration & dosage , Polyphenols/administration & dosage , Verrucomicrobia/drug effects , Animals , Gastrointestinal Microbiome/drug effects , Gastrointestinal Tract/metabolism , Gastrointestinal Tract/microbiology , Humans , Metabolic Syndrome/metabolism , Metabolic Syndrome/microbiology , Mice , Vaccinium macrocarpon/chemistry , Verrucomicrobia/growth & development , Verrucomicrobia/metabolismABSTRACT
OBJECTIVE: The increasing prevalence of obesity and type 2 diabetes (T2D) demonstrates the failure of conventional treatments to curb these diseases. The gut microbiota has been put forward as a key player in the pathophysiology of diet-induced T2D. Importantly, cranberry (Vaccinium macrocarpon Aiton) is associated with a number of beneficial health effects. We aimed to investigate the metabolic impact of a cranberry extract (CE) on high fat/high sucrose (HFHS)-fed mice and to determine whether its consequent antidiabetic effects are related to modulations in the gut microbiota. DESIGN: C57BL/6J mice were fed either a chow or a HFHS diet. HFHS-fed mice were gavaged daily either with vehicle (water) or CE (200â mg/kg) for 8â weeks. The composition of the gut microbiota was assessed by analysing 16S rRNA gene sequences with 454 pyrosequencing. RESULTS: CE treatment was found to reduce HFHS-induced weight gain and visceral obesity. CE treatment also decreased liver weight and triglyceride accumulation in association with blunted hepatic oxidative stress and inflammation. CE administration improved insulin sensitivity, as revealed by improved insulin tolerance, lower homeostasis model assessment of insulin resistance and decreased glucose-induced hyperinsulinaemia during an oral glucose tolerance test. CE treatment was found to lower intestinal triglyceride content and to alleviate intestinal inflammation and oxidative stress. Interestingly, CE treatment markedly increased the proportion of the mucin-degrading bacterium Akkermansia in our metagenomic samples. CONCLUSIONS: CE exerts beneficial metabolic effects through improving HFHS diet-induced features of the metabolic syndrome, which is associated with a proportional increase in Akkermansia spp.