Effect of probiotics on vaginal Ureaplasma parvum in women suffering from unexplained infertility.

RESEARCH QUESTION: Does oral probiotic supplementation influence the relative abundance of different vaginal microbiota in women experiencing infertility? DESIGN: A prospective, monocentric randomized controlled trial. To study the influence of probiotics on infertility, 80 patients with primary or secondary infertility were included. Patients were assigned to either a probiotic treatment or a control group. Participants in the treatment group (n = 40) took one sachet (2 g) a day of a defined probiotic supplement limiting Lactobacillus strains. Patients in the control group did not receive any additional probiotic supplements. Vaginal samples were taken on day 20 of the menstrual cycle and 4 weeks later, on day 20, of the consecutive cycle. Subsequently, 16s rRNA gene analysis of the vaginal samples was conducted. RESULTS: After the intervention phase, no effects on alpha diversity resulting from treatment could be observed. The between sample diversity of different women (beta diversity) at baseline had no effects of age, treatment group or body mass index. Primary or secondary sterility, however, had a significant effect on community. Three clusters (Lactobacillus crispatus, Lactobacillus iners and Lactobacillus gasseri) were identified as the leading representatives. Furthermore, patients treated with probiotics showed limited growth of Ureaplasma parvum compared with the control group (P = 0.021). CONCLUSIONS: This study points to a possible protective effect of probiotic supplements on the vaginal microbiota. It is tempting to speculate that this effect assists in containing the growth of non-beneficial bacteria and helps to prevent or cure a dysbiotic vaginal flora.

Stress gets into the belly: Early life stress and the gut microbiome.

Research has established that stress "gets under the skin," impacting neuroendocrine and neuroimmune pathways to influence risk for physical and mental health outcomes. These effects can be particularly significant for early life stress (ELS), or adverse childhood experiences (ACEs). In this review, we explore whether stress gets "into the belly," that is, whether psychosocial stress affects the gut microbiome. We review animal and human research utilizing a variety of stress paradigms (acute laboratory stressors, chronic stress, stressful life events, perceived stress, ELS, in utero stress) and their impacts on the gut microbiota, with a particular focus on ELS. We also review data on dietary interventions to moderate impact of stress on the gut microbiome. Our review suggests strong evidence that acute laboratory stress, chronic stress, and ELS affect the gut microbiota in rodents, and growing evidence that perceived stress and ELS may impact the gut microbiota in humans. Emerging data also suggests, particularly in rodents, that dietary interventions such as omega-3 fatty acids and pre- and pro-biotics may buffer against the effects of stress on the gut microbiome, but more research is needed. In sum, growing evidence suggests that stress impacts not only the neuroendocrine and neuroimmune axes, but also the microbiota-gut-brain-axis, providing a pathway by which stress may get "into the belly" to influence health risk.

Microbiota, a New Playground for the Omega-3 Polyunsaturated Fatty Acids in Cardiovascular Diseases.

Several cardioprotective mechanisms attributed to Omega-3 polyunsaturated fatty acids (PUFAs) have been studied and widely documented. However, in recent years, studies have supported the concept that the intestinal microbiota can play a much larger role than we had anticipated. Microbiota could contribute to several pathologies, including cardiovascular diseases. Indeed, an imbalance in the microbiota has often been reported in patients with cardiovascular disease and produces low-level inflammation. This inflammation contributes to, more or less, long-term development of cardiovascular diseases. It can also worsen the symptoms and the consequences of these pathologies. According to some studies, omega-3 PUFAs in the diet could restore this imbalance and mitigate its harmful effects on cardiovascular diseases. Many mechanisms are involved and included: (1) a reduction of bacteria producing trimethylamine (TMA); (2) an increase in bacteria producing butyrate, which has anti-inflammatory properties; and (3) a decrease in the production of pro-inflammatory cytokines. Additionally, omega-3 PUFAs would help maintain better integrity in the intestinal barrier, thereby preventing the translocation of intestinal contents into circulation. This review will summarize the effects of omega-3 PUFAs on gut micro-biota and the potential impact on cardiac health.

Probiotic intervention as a potential therapeutic for managing gestational disorders and improving pregnancy outcomes.

Recent molecular investigations have significantly developed our knowledge of the characteristics of the reproductive microbiome and their associations with host responses to provide an ideal milieu for the development of the embryo during the peri-implantation period and throughout pregnancy as well as to provide a successful in vitro fertilization and appropriate reproductive outcomes. In this context, the establishment of microbial homeostasis in the female reproductive tract, in various physiological periods, is a substantial challenge, which appears the application of probiotics can facilitate the achievement of this goal. So that, currently, probiotics due to its safe and natural features can be considered as a novel biotherapeutic approach. In this review, we comprehensively discuss the bacterial, fungal, and viral diversity detected in the reproductive tract, and their associations with the establishment of dysbiosis/eubiosis conditions as well as we present the significant outcomes on probiotic intervention as an efficient biotherapeutic strategy for management of gestational disorders and improve pregnancy outcomes.

Nutritional and therapeutic approaches for protecting human gut microbiota from psychotropic treatments.

Emerging evidence highlighted the essential role played by the microbiota-gut-brain axis in maintaining human homeostasis, including nutrition, immunity, and metabolism. Much recent work has linked the gut microbiota to many psychiatric and neurodegenerative disorders such as depression, schizophrenia, and Alzheimer's disease. Shared gut microbiota alterations or dysbiotic microbiota have been identified in these separate disorders relative to controls. Much attention has focused on the bidirectional interplay between the gut microbiota and the brain, establishing gut dysbiotic status as a critical factor in psychiatric disorders. Still, the antibiotic-like effect of psychotropic drugs, medications used for the treatment of these disorders, on gut microbiota is largely neglected. In this review, we summarize the current findings on the impact of psychotropics on gut microbiota and how their antimicrobial potency can trigger dysbiosis. We also discuss the potential therapeutic strategies, including probiotics, prebiotics, and fecal transplantation, to attenuate the dysbiosis related to psychotropics intake.

Pinto beans modulate the gut microbiome, augment MHC II protein, and antimicrobial peptide gene expression in mice fed a normal or western-style diet.

The onset of type 2 diabetes in obesity is associated with gut dysbiosis and a failure to confine commensal bacteria and toxins to the gut lumen while prebiotics may prevent these effects. This study evaluated the effects of pinto beans (PB) supplementation on cecal bacteria, short-chain fatty acids (SCFAs), distal ileal antigen presentation marker (major histocompatibility complex [MHC] II) and antimicrobial peptide genes during short-term high-fat, high sucrose (HFS) feeding. Six-week-old, male C57BL/6J mice were randomly assigned to four groups (n=12/group), and fed a control (C) or HFS diet with or without cooked PB (10%, wt/wt) for 30 days. Supplemental PB in both the C and HFS diets decreased the abundance of Tenericutes and the sulfate-reducing bacteria Bilophila. In contrast, PB raised the abundance of taxa within the SCFAs-producing family, Lachnospiraceae, compared to groups without PB. Consequently, fecal butyric acid was significantly higher in PB-supplemented groups compared to C and HFS groups. PB reversed the HFS-induced ablation of the distal ileal STAT3 phosphorylation, and up-regulated antimicrobial peptide genes (Reg3γ and Reg3ß). Furthermore, the expression of MHC II protein was elevated in the PB supplemented groups compared to C and HFS. Tenericutes and Bilophilia negatively correlated with activated STAT3 and MHC II proteins. Finally, supplemental PB improved fasting blood glucose, glucose tolerance and suppressed TNFα and inducible nitric oxide synthase mRNA in the visceral adipose tissue. Put together, the beneficial impact of PB supplementation on the gut may be central to its potential to protect against diet-induced inflammation and impaired glucose tolerance.

Sulfated polysaccharides from Undaria pinnatifida improved high fat diet-induced metabolic syndrome, gut microbiota dysbiosis and inflammation in BALB/c mice.

Undaria pinnatifida was shown to reduce serum lipids and fat accumulation and produce beneficial effect on type 2 diabetes, but its effect on intestinal micro-ecology remains unclear. This study showed that sulfated polysaccharides from U. pinnatifida (UPSP) reduced weight gain, fat accumulation and metabolic disorders in mice fed with high fat diet (HFD). UPSP not only alleviated HFD-induced microbiota dysbiosis indicated as increased abundances of some Bacteroidales members that had positive correlations with the improvement of physiological indexes, but also maintained gut barrier integrity and reduced metabolic endotoxemia. A dose-effect relationship was observed between the dose of UPSP and its effect on some physiological indexes, gut microbiota community and nutrient utilization. The in vitro result showed that the use of Bacteroides species within Bacteroidales on UPSP was species-dependent, and the dose of UPSP affected the growth properties of some Bacteroides species. It implied that UPSP can be considered as prebiotic agent to prevent gut dysbiosis and obesity-related diseases in obese individuals.

Gastrointestinal Disorders and Metabolic Syndrome: Dysbiosis as a Key Link and Common Bioactive Dietary Components Useful for their Treatment.

Gastrointestinal (GI) diseases, which include gastrointestinal reflux disease, gastric ulceration, inflammatory bowel disease, and other functional GI disorders, have become prevalent in a large part of the world population. Metabolic syndrome (MS) is cluster of disorders including obesity, hyperglycemia, hyperlipidemia, and hypertension, and is associated with high rate of morbidity and mortality. Gut dysbiosis is one of the contributing factors to the pathogenesis of both GI disorder and MS, and restoration of normal flora can provide a potential protective approach in both these conditions. Bioactive dietary components are known to play a significant role in the maintenance of health and wellness, as they have the potential to modify risk factors for a large number of serious disorders. Different classes of functional dietary components, such as dietary fibers, probiotics, prebiotics, polyunsaturated fatty acids, polyphenols, and spices, possess positive impacts on human health and can be useful as alternative treatments for GI disorders and metabolic dysregulation, as they can modify the risk factors associated with these pathologies. Their regular intake in sufficient amounts also aids in the restoration of normal intestinal flora, resulting in positive regulation of insulin signaling, metabolic pathways and immune responses, and reduction of low-grade chronic inflammation. This review is designed to focus on the health benefits of bioactive dietary components, with the aim of preventing the development or halting the progression of GI disorders and MS through an improvement of the most important risk factors including gut dysbiosis.

Effect of a Nutritional Intervention on the Intestinal Microbiota of Vertically HIV-Infected Children: The Pediabiota Study.

AIMS: The gut microbiota exerts a critical influence in the immune system. The gut microbiota of human virus immunodeficiency (HIV)-infected children remains barely explored. We aimed to characterize the fecal microbiota in vertically HIV-infected children and to explore the effects of its modulation with a symbiotic nutritional intervention. METHODS: a pilot, double blind, randomized placebo-controlled study including HIV-infected children who were randomized to receive a nutritional supplementation including prebiotics and probiotics or placebo for four weeks. HIV-uninfected siblings were recruited as controls. The V3-V4 region of the 16S rRNA gene was sequenced in fecal samples. RESULTS: 22 HIV-infected children on antiretroviral therapy (ART) and with viral load (VL) <50/mL completed the follow-up period. Mean age was 11.4 ± 3.4 years, eight (32%) were male. Their microbiota showed reduced alpha diversity compared to controls and distinct beta diversity at the genus level (Adonis p = 0.042). Patients showed decreased abundance of commensals Faecalibacterium and an increase in Prevotella, Akkermansia and Escherichia. The nutritional intervention shaped the microbiota towards the control group, without a clear directionality. CONCLUSIONS: Vertical HIV infection is characterized by changes in gut microbiota structure, distinct at the compositional level from the findings reported in adults. A short nutritional intervention attenuated bacterial dysbiosis, without clear changes at the community level. SUMMARY: In a group of 24 vertically HIV-infected children, in comparison to 11 uninfected controls, intestinal dysbiosis was observed despite effective ART. Although not fully effective to restore the microbiota, a short intervention with pre/probiotics attenuated bacterial dysbiosis.

The Beneficial Effects of Lippia Citriodora Extract on Diet-Induced Obesity in Mice Are Associated with Modulation in the Gut Microbiota Composition.

SCOPE: Obesity is characterized by a dysfunction in the adipose tissue and an inflammatory subclinical state leading to insulin resistance and increased risk of cardiovascular diseases. It is also associated with intestinal dysbiosis that contributes to inflammation development. Lippia citriodora (LCE) contains high levels of polyphenolpropanoids and has shown promising results in obesity. The aim of this study is to investigate a well-characterized extract of LCE in a model of metabolic syndrome in mice, focusing on its effects on metabolic tissues, endothelial dysfunction, and microbiome. METHODS: Mice are fed a high fat diet (HFD) for six weeks and treated daily with LCE (1, 10, and 25 mg kg-1 ). Glucose and lipid metabolism is investigated. The inflammatory state in the metabolic tissues and the intestinal microbiota composition are characterized, as well as the endothelium-dependent vasodilator response to acetylcholine. RESULTS: LCE reduces fat accumulation and improves plasma glycemic and lipid profiles, as well as the inflammatory process and vascular dysfunction. Moreover, LCE lessens intestinal dysbiosis, as it reduces the Firmicutes/Bacteroidetes ratio and increases Akkermansia abundance in comparison with untreated HFD mice. CONCLUSION: The antiobesity therapeutic properties of LCE are most probably mediated by the synergic effects of its bioactive compounds.

Grape Extract Activates Brown Adipose Tissue Through Pathway Involving the Regulation of Gut Microbiota and Bile Acid.

SCOPE: Although the physiological function of grape extract (GE) has long been recognized, the precise mechanism remains obscure. This study is designed to investigate the effects of GE on metabolism and the association between GE activation of brown adipose tissue (BAT) and the restoration of gut microbiota (GM). METHODS AND RESULTS: Diet-induced obese mice are used to investigate the function of GE. GE administration increases energy metabolism and prevents obesity. Also, GE restores the dysbiosis of GM by augmenting the observed species, enhancing the Firmicutes-to-Bacteroidetes ratio and increasing the abundance of the Bifidobacteria, Akkermansia, and Clostridia genera. This restoration of GM alters the bile acid (BA) pool in the serum. The abundance of Akkermansia, Clostridium, and Bifidobacterium is negatively correlated with the concentrations of TαMCA, TßMCA, and TCA but is positively correlated with DCA. The changes in BA promoted TGR5 in BAT, which contributed to thermogenesis. The metabolites of GE in blood do not stimulate TGR5 in vitro. CONCLUSION: GE stimulates the thermogenesis of BAT through a pathway involving the regulation of GM and BA in diet-induced obese mice. This study reveals the mechanism by which dietary polyphenols promote thermogenesis by regulating BA, which is altered by GM.

High-Salt Diet-Induced Gastritis in C57BL/6 Mice is Associated with Microbial Dysbiosis and Alleviated by a Buckwheat Diet.

SCOPE: A high-salt diet is a cause of gastritis, but the associated mechanism remains unclear. Recent studies have shown that gastric flora is associated with a variety of stomach diseases, but it is not known whether gastric flora is involved in gastritis induced by a high-salt diet. METHODS AND RESULTS: Gastritis is successfully induced in C57BL/6 mice fed a high-salt diet (salt: 5% NaCl) for four weeks. Through 16S rRNA gene sequencing, the composition of the stomach microbiota of mice fed normal and high-salt diets are compared, the results of which show that the high-salt diet induces significant changes in the gastric flora. Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) is used to predict the function of the microbiota in the stomach of mice, and the results indicate that a high-salt diet leads to a decrease in the ability of the gastric microbiota to metabolize polysaccharides and vitamins. A buckwheat diet is used to treat gastritis. The results show gastritis induced by the high-salt diet is significantly alleviated, and the dysbiosis in the stomach also improved. CONCLUSION: Buckwheat diet may be one of the ways to prevent and treat gastritis caused by a high-salt diet.

Dietary Supplementation of Black Rice Anthocyanin Extract Regulates Cholesterol Metabolism and Improves Gut Microbiota Dysbiosis in C57BL/6J Mice Fed a High-Fat and Cholesterol Diet.

SCOPE: This study explores the beneficial effects of dietary supplementation of black rice anthocyanin extract (BRAE) on cholesterol metabolism and gut dysbiosis. METHODS AND RESULTS: C57BL/6J mice are grouped into the normal chow diet group (NCD), the high-fat and the cholesterol diet group (HCD), and three treatment groups feeding HCD supplemented with various dosage of BRAE for 12 weeks. Results reveal that BRAE alleviates the increased body weight, serum triglyceride (TG), total cholesterol (TC), non-high-density lipoprotein cholesterol levels (non-HDL-C), and increased fecal sterols excretion and caecal short-chain fatty acids (SCFAs) concentration in HCD-induced hypercholesterolemic mice. Moreover, BRAE decreases hepatic TC content through the fundamental regulation of body energy balance gene, adenosine 5'-monophosphate activated protein kinase α (AMPKα). Meanwhile, BRAE improves the genes expression involved in cholesterol uptake and efflux, and preserves CYP7A1, ATP-binding cassette subfamily G member 5/8 mRNA expression, and the relative abundance of gut microbiota. Additionally, the antibiotic treatment experiment indicates that the beneficial effects of BRAE in reducing hypocholesterolemia risk largely depends on the gut microbiota homeostasis. CONCLUSION: BRAE supplement could be a beneficial treatment option for preventing HCD-induced hypocholesterolemia and related metabolic syndromes.

Effect of Short-Term Dietary Intervention and Probiotic Mix Supplementation on the Gut Microbiota of Elderly Obese Women.

Accumulating literature is providing evidence that the gut microbiota is involved in metabolic disorders, but the question of how to effectively modulate it to restore homeostasis, especially in the elderly, is still under debate. In this study, we profiled the intestinal microbiota of 20 elderly obese women (EO) at the baseline (T0), after 15 days of hypocaloric Mediterranean diet administered as part of a nutritional-metabolic rehabilitation program for obesity (T1), and after a further 15 days of the same diet supplemented with a probiotic mix (T2). Fecal samples were characterized by Illumina MiSeq sequencing of the 16S rRNA gene. The EO microbiota showed the typical alterations found in obesity, namely, an increase in potential pro-inflammatory components (i.e., Collinsella) and a decrease in health-promoting, short-chain fatty acid producers (i.e., Lachnospiraceae and Ruminococcaceae members), with a tendency to reduced biodiversity. After 15 days of the rehabilitation program, weight decreased by (2.7 ± 1.5)% and the gut microbiota dysbiosis was partially reversed, with a decline of Collinsella and an increase in leanness-related taxa. During the next 15 days of diet and probiotics, weight dropped further by (1.2 ± 1.1)%, markers of oxidative stress improved, and Akkermansia, a mucin degrader with beneficial effects on host metabolism, increased significantly. These findings support the relevant role of a correct dietetic approach, even in the short term, to modulate the EO gut microbiota towards a metabolic health-related configuration, counteracting the increased risk of morbidity in these patients.

Prebiotic UG1601 mitigates constipation-related events in association with gut microbiota: A randomized placebo-controlled intervention study.

BACKGROUND: Constipation is a common functional gastrointestinal disorder and its etiology is multifactorial. Growing evidence suggests that intestinal dysbiosis is associated with the development of constipation. Prebiotics are subjected to bacterial fermentation in the gut to produce short-chain fatty acids (SCFAs), which can help relieve constipation symptoms. The prebiotic UG1601 consists of inulin, lactitol, and aloe vera gel, which are known laxatives, but randomized, controlled clinical trials that examine the effects of this supplement on gut microbiota composition are lacking. AIM: To assess the efficacy of the prebiotic UG1601 in suppressing constipation-related adverse events in subjects with mild constipation. METHODS: Adults with a stool frequency of less than thrice a week were randomized to receive either prebiotics or a placebo supplement for 4 wk. All participants provided their fecal and blood samples at baseline and at the end of intervention. Gastrointestinal symptoms and stool frequency were evaluated. The concentrations of serum endotoxemia markers and fecal SCFAs were determined. The relative abundance of SCFA-producing bacteria and the gut microbial community in the responders and non-responders in the prebiotics supplementation group were evaluated. RESULTS: There were no significant differences in gastrointestinal symptoms between groups, although the prebiotic group showed greater symptom improvement. However, after prebiotic usage, serum cluster of differentiation (CD) 14 and lipopolysaccharide (LPS) concentrations were significantly decreased (CD14, P = 0.012; LPS, P < 0.001). The change in LPS concentration was significantly larger in the prebiotic group than in the placebo group (P < 0.001). Fecal SCFAs concentrations did not differ between groups, while the relative abundance of Roseburia hominis, a major butyrate producer, was significantly increased in the prebiotic group (P = 0.045). The abundances of the phylum Firmicutes and the family Lachnospiraceae (phylum Firmicutes, class Clostridia) (P = 0.009) were decreased in the responders within the prebiotic group. In addition, the proportions of the phylum Firmicutes, the class Clostridia, and the order Clostridiales were inversely correlated with several fecal SCFAs (P < 0.05). CONCLUSION: Alterations in gut microbiota composition, including a decrease in the phylum Firmicutes and an increase in butyrate-producing bacteria, following prebiotic UG1601 supplementation might help alleviate symptom scores and endotoxemia.

Dietary cranberry suppressed colonic inflammation and alleviated gut microbiota dysbiosis in dextran sodium sulfate-treated mice.

Increased consumption of fruits may decrease the risk of chronic inflammatory diseases including inflammatory bowel disease (IBD). Gut microbiota dysbiosis plays an important etiological role in IBD. However, the mechanisms of action underlying the anti-inflammatory effects of dietary cranberry (Vaccinium macrocarpon) in the colon and its role on gut microbiota were unclear. In this study, we determined the anti-inflammatory efficacy of whole cranberry in a mouse model of dextran sodium sulfate (DSS)-induced colitis, as well as its effects on the structure of gut microbiota. The results showed that dietary cranberry significantly decreased the severity of colitis in DSS-treated mice, evidenced by increased colon length, and decreased disease activity and histologic score of colitis in DSS-treated mice compared to the positive control group (p < 0.05). Moreover, the colonic levels of pro-inflammatory cytokine (IL-1ß, IL-6 and TNF-α) were significantly reduced by cranberry supplementation (p < 0.05). Analysis of the relative abundance of fecal microbiota in phylum and genus levels revealed that DSS treatment significantly altered the microbial structure of fecal microbiota in mice. α diversity was significantly decreased in the DSS group, compared to the healthy control group. But, cranberry treatment significantly improved DSS-induced decline in α-diversity. Moreover, cranberry treatment partially reversed the change of gut microbiota in colitic mice by increasing the abundance of potential beneficial bacteria, for example, Lactobacillus and Bifidobacterium, and decreasing the abundance of potential harmful bacteria, such as Sutterella and Bilophila. Overall, our results for the first time demonstrated that modification of gut microbiota by dietary whole cranberry might contribute to its inhibitory effects against the development of colitis in DSS-treated mice.

Treatment strategies against diabetes: Success so far and challenges ahead.

The growing disease burden of diabetes mellitus is an important public health concern, affecting over 400 million people globally. This epidemic, if not controlled in time, leads to life threatening complications, compromise in quality of life, and eventually mortality. Over time, many attempts have been made for the effective treatment of diabetes but true success has never been achieved. Pharmacological and non-pharmacological approaches for the treatment of hyperglycaemia have been ever-evolving due to limitations of current therapies. Non pharmacological management which includes diet management and exercise, has been the primary focus for self-management of diabetes. The pharmacological management includes oral antihyperglycaemics, phytoconstituents, and combination products. Advancements such as nanocarrier delivery systems have been made in drug delivery to overcome the challenges such as poor bioavailability associated with conventional dosage forms currently employed in diabetes treatment. In recent years, much emphasis has been given to synbiotics that act on gut microbiota, as an emerging therapy for diabetes. The current review discusses different treatment strategies for diabetes management starting from insulin therapy to synbiotics. The combination of herbal phytoconstituents with synthetic drugs, synthetic drug combinations, novel drug delivery systems for insulin are highlighted. Moreover, the role of gut dysbiosis in diabetes and its treatment by administration of synbiotics in various clinical as well as non clinical studies has been discussed in detail.

Glycerol-Monolaurate-Mediated Attenuation of Metabolic Syndrome is Associated with the Modulation of Gut Microbiota in High-Fat-Diet-Fed Mice.

SCOPE: The gut microbiota plays an important role in the development of diet-induced obesity and metabolic syndrome. Glycerol monolaurate (GML), a widely consumed food emulsifier, is reported to promote metabolic disorder and gut microbiota dysbiosis in low-dose supplementation upon low-fat-diet feeding. However, little is known about whether GML produce the same effects in mice fed a high-fat diet (HFD). METHODS AND RESULTS: C57BL/6 mice are fed a HFD with or without GML supplementation (150, 300, and 450 mg kg-1 ) for 10 weeks. The results demonstrated that higher GML treatment (450 mg kg-1 ) ameliorates HFD-induced metabolic disorders, supported by prevented visceral fat deposition, improved hyperlipidemia, modulated hepatic lipid metabolism, and reduced serum proinflammatory cytokine, TNF-α. Additionally, all doses of GML attenuated circulating lipopolysaccharide load and insulin resistance. Notably, GML ameliorates HFD-induced gut microbiota dysbiosis, with increases in Bacteroides uniformis, Akkermansia, Bifidobacterium, and Lactobacillus and decreases in Escherichia coli, Lactococcus, and Flexispira. Spearman's correlation analysis indicates that these enriched specific genera are significantly associated with the metabolic improvements of GML. CONCLUSION: The findings identify the links between gut microbiota and GML-induced metabolic improvements, suggesting that the attenuation of HFD-induced metabolic disorders by higher GML supplementation may occur through targeting gut microbiota.

From gut microbiota dysfunction to obesity: could short-chain fatty acids stop this dangerous course?

Study of the interactions between the gut microbiota and brain-gut axis represents a very appealing approach to increasing our knowledge about the mechanisms leading to obesity and obesity-related diseases. The aim of this review is to focus on the effects of short-chain fatty acids (SCFAs), which are the main products of gut microbial fermentation from non-digestible carbohydrates in the colon, on the gut-brain axis. Evidence is accumulating regarding the role of SCFAs in the fine-tuning of the gut-brain axis, a feedback system which is vital not only for the proper maintenance of gastrointestinal and metabolic functions, but also for the regulation of food intake and energy expenditure. SCFAs are thought to play a key role in increasing the host capacity to harvest excess energy from the diet. SCFAs, however, can exert their effects on the host metabolism via multiple complementary pathways. Metabolic, inflammatory, and neural pathways can be regulated by SCFAs, which can act by sensing nutritional status, thereby maintaining body energy homeostasis. SCFA production from prebiotic consumption is the rationale for targeting intestinal mechanisms to increase energy expenditure and thereby reduce obesity risk.

Green tea extract prevents obesity in male mice by alleviating gut dysbiosis in association with improved intestinal barrier function that limits endotoxin translocation and adipose inflammation.

Gut-derived endotoxin translocation provokes obesity by inducing TLR4/NFκB inflammation. We hypothesized that catechin-rich green tea extract (GTE) would protect against obesity-associated TLR4/NFκB inflammation by alleviating gut dysbiosis and limiting endotoxin translocation. Male C57BL/6J mice were fed a low-fat (LF) or high-fat (HF) diet containing 0% or 2% GTE for 8 weeks. At Week 7, fluorescein isothiocyanate (FITC)-dextran was administered by oral gavage before assessing its serum concentrations as a gut permeability marker. HF-feeding increased (P<.05) adipose mass and adipose expression of genes involved in TLR4/NFκB-dependent inflammation and macrophage activation. GTE attenuated HF-induced obesity and pro-inflammatory gene expression. GTE in HF mice decreased serum FITC-dextran, and attenuated portal vein and circulating endotoxin concentrations. GTE in HF mice also prevented HF-induced decreases in the expression of intestinal tight junction proteins (TJPs) and hypoxia inducible factor-1α while preventing increases in TLR4/NFκB-dependent inflammatory genes. Gut microbial diversity was increased, and the Firmicutes:Bacteroidetes ratio was decreased, in HF mice fed GTE compared with HF controls. GTE in LF mice did not attenuate adiposity but decreased endotoxin and favorably altered several gut bacterial populations. Serum FITC-dextran was correlated with portal vein endotoxin (P<.001; rP=0.66) and inversely correlated with colonic mRNA levels of TJPs (P<.05; rP=-0.38 to -0.48). Colonic TJPs mRNA were inversely correlated with portal endotoxin (P<.05; rP=-0.33 to -0.39). These data suggest that GTE protects against diet-induced obesity consistent with a mechanism involving the gut-adipose axis that limits endotoxin translocation and consequent adipose TLR4/NFκB inflammation by improving gut barrier function.