Beneficial Effects of Newly Isolated Akkermansia muciniphila Strains from the Human Gut on Obesity and Metabolic Dysregulation

The identification of new probiotics with anti-obesity properties has attracted considerable interest. In the present study, the anti-obesity activities of Akkermansia muciniphila (A. muciniphila) strains isolated from human stool samples and their relationship with the gut microbiota were evaluated using a high fat-diet (HFD)-fed mice model. Three strains of A. muciniphila were chosen from 27 isolates selected based on their anti-lipogenic activity in 3T3-L1 cells. The anti-lipogenic, anti-adipogenic and anti-obesity properties of these three strains were evaluated further in HFD-induced obese mice. The animals were administered these strains six times per week for 12 weeks. The treatment improved the HFD-induced metabolic disorders in mice in terms of the prevention of body weight gain, caloric intake and reduction in the weights of the major adipose tissues and total fat. In addition, it improved glucose homeostasis and insulin sensitivity. These effects were also associated with the inhibition of low-grade intestinal inflammation and restoration of damaged gut integrity, prevention of liver steatosis and improvement of hepatic function. These results revealed a difference in the distribution pattern of the gut microbial communities between groups. Therefore, the gut microbial population modulation, at least in part, might contribute to the beneficial impact of the selected A. muciniphila strains against metabolic disorders.

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Consumption of Wild Rice (Zizania latifolia) Prevents Metabolic Associated Fatty Liver Disease through the Modulation of the Gut Microbiota in Mice Model

International Journal of Molecular Sciences ◽

10.3390/ijms21155375 ◽

2020 ◽

Vol 21 (15) ◽

pp. 5375

Author(s):

Xiao-Dong Hou ◽

Ning Yan ◽

Yong-Mei Du ◽

Hui Liang ◽

Zhong-Feng Zhang ◽

...

Keyword(s):

Liver Disease ◽

Gut Microbiota ◽

Fatty Liver ◽

Wild Rice ◽

Fatty Liver Disease ◽

Liver Steatosis ◽

Chow Diet ◽

Low Grade ◽

Mice Model ◽

16S Rrna Pyrosequencing

Metabolic associated fatty liver disease (MAFLD) due to excess weight and obesity threatens public health worldwide. Gut microbiota dysbiosis contributes to obesity and related diseases. The cholesterol-lowering, anti-inflammatory, and antioxidant effects of wild rice have been reported in several studies; however, whether it has beneficial effects on the gut microbiota is unknown. Here, we show that wild rice reduces body weight, liver steatosis, and low-grade inflammation, and improves insulin resistance in high-fat diet (HFD)-fed mice. High-throughput 16S rRNA pyrosequencing demonstrated that wild rice treatment significantly changed the gut microbiota composition in mice fed an HFD. The richness and diversity of the gut microbiota were notably decreased upon wild rice consumption. Compared with a normal chow diet (NCD), HFD feeding altered 117 operational taxonomic units (OTUs), and wild rice supplementation reversed 90 OTUs to the configuration in the NCD group. Overall, our results suggest that wild rice may be used as a probiotic agent to reverse HFD-induced MAFLD through the modulation of the gut microbiota.

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Beta-Aminoisobutyric Acid Inhibits Hypothalamic Inflammation by Reversing Microglia Activation

Cells ◽

10.3390/cells8121609 ◽

2019 ◽

Vol 8 (12) ◽

pp. 1609 ◽

Cited By ~ 3

Author(s):

Byong Seo Park ◽

Thai Hien Tu ◽

Hannah Lee ◽

Da Yeon Jeong ◽

Sunggu Yang ◽

...

Keyword(s):

High Fat Diet ◽

Microglial Activation ◽

Metabolic Disorders ◽

Body Weight Gain ◽

Aminoisobutyric Acid ◽

Beneficial Effects ◽

Tightly Coupled ◽

Hypothalamic Inflammation ◽

Inflammatory Processes

Beta-aminoisobutyric acid (BAIBA), a natural thymine catabolite, is involved in the beneficial effects of exercise on metabolic disorders. In particular, it has been reported to reverse the inflammatory processes observed in the peripheral organs of animal models of obesity. Therefore, this study aimed to investigate whether BAIBA improves hypothalamic inflammation, which is also tightly coupled with the development of obesity. We observed that treatment with BAIBA effectively reversed palmitic acid-induced hypothalamic inflammation and microglial activation in vivo. Consistent with these findings, we confirmed that BAIBA reversed body weight gain and increased adiposity observed in mice fed with a high-fat diet. Collectively, the current findings evidence the beneficial impacts of BAIBA on the imbalance of energy metabolism linked to hypothalamic inflammation.

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Cocoa Polyphenols and Their Potential Benefits for Human Health

Oxidative Medicine and Cellular Longevity ◽

10.1155/2012/906252 ◽

2012 ◽

Vol 2012 ◽

pp. 1-23 ◽

Cited By ~ 89

Author(s):

I. Andújar ◽

M. C. Recio ◽

R. M. Giner ◽

J. L. Ríos

Keyword(s):

Oxidative Stress ◽

Human Health ◽

Metabolic Disorders ◽

Ldl Cholesterol ◽

Intestinal Inflammation ◽

Inflammatory Diseases ◽

Antioxidant Properties ◽

Neutrophil Infiltration ◽

Beneficial Effects ◽

Potential Benefits

This paper compiles the beneficial effects of cocoa polyphenols on human health, especially with regard to cardiovascular and inflammatory diseases, metabolic disorders, and cancer prevention. Their antioxidant properties may be responsible for many of their pharmacological effects, including the inhibition of lipid peroxidation and the protection of LDL-cholesterol against oxidation, and increase resistance to oxidative stress. The phenolics from cocoa also modify the glycemic response and the lipid profile, decreasing platelet function and inflammation along with diastolic and systolic arterial pressures, which, taken together, may reduce the risk of cardiovascular mortality. Cocoa polyphenols can also modulate intestinal inflammation through the reduction of neutrophil infiltration and expression of different transcription factors, which leads to decreases in the production of proinflammatory enzymes and cytokines. The phenolics from cocoa may thus protect against diseases in which oxidative stress is implicated as a causal or contributing factor, such as cancer. They also have antiproliferative, antimutagenic, and chemoprotective effects, in addition to their anticariogenic effects.

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The Aryl Hydrocarbon Receptor (AhR) Mediates the Counter-Regulatory Effects of Pelargonidins in Models of Inflammation and Metabolic Dysfunctions

Nutrients ◽

10.3390/nu11081820 ◽

2019 ◽

Vol 11 (8) ◽

pp. 1820 ◽

Cited By ~ 9

Author(s):

Michele Biagioli ◽

Adriana Carino ◽

Chiara Fiorucci ◽

Giannamaria Annunziato ◽

Silvia Marchianò ◽

...

Keyword(s):

Aryl Hydrocarbon Receptor ◽

Natural Compound ◽

Intestinal Inflammation ◽

Body Weight Gain ◽

Liver Steatosis ◽

Signs And Symptoms ◽

Dependent Manner ◽

Aryl Hydrocarbon

Pelargonidins are anthocyanidins thought to be beneficial for the human health, although controversies exist over the doses needed and the unclear mechanism of action, along with poor systemic bioavailability. One putative target of pelargonidins is the aryl hydrocarbon receptor (AhR). A synthetic pelargonidin (Mt-P) was synthesized by the methylation of the pelargonidin (the natural compound indicated as P). Mt-P transactivated the AhR with an EC50 of 1.97 µM and was ~2-fold more potent than the natural compound. In vitro Mt-P attenuated pro-inflammatory activities of Raw264.7 macrophage cells in an AhR-dependent manner. In vivo, administration of the Mt-P in Balb/c mice resulted in a dose-dependent attenuation of signs and symptoms of colitis induced by TNBS. A dose of 5 mg/kg Mt-P, but not the natural compound P, reversed intestinal inflammation and increased expression of Tnf-α, Ifn-ƴ, and Il-6, while promoted the expansion of regulatory T cells and M2 macrophages. In C57BL/6J mice fed a high fat diet (HFD), Mt-P attenuated body weight gain, intestinal and liver inflammation, and ameliorated insulin sensitivity, while worsened liver steatosis by up-regulating the liver expression of Cd36 and Apo100b. These effects were abrogated by AhR gene ablation. Mt-P is a synthetic pelargonidin endowed with robust AhR agonist activity that exerts beneficial effects in murine models of inflammation and metabolic dysfunction.

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Nitrooleic Acid Attenuates Lipid Metabolic Disorders and Liver Steatosis in DOCA-Salt Hypertensive Mice

PPAR Research ◽

10.1155/2015/480348 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Haiping Wang ◽

Jing Sun ◽

Zhanjun Jia ◽

Tianxin Yang ◽

Liang Xu ◽

...

Keyword(s):

Liver Lipid ◽

Liver Steatosis ◽

Control Group ◽

Peroxisome Proliferator ◽

Mice Model ◽

Nonesterified Fatty Acids ◽

Liver Lipid Content ◽

Beneficial Effects ◽

Cholesterol Levels ◽

Peroxisome Proliferator Activated Receptors

Nitrooleic acid (OA-NO2) is endogenous ligands for peroxisome proliferator-activated receptors. The present study was aimed at investigating the beneficial effects of OA-NO2on the lipid metabolism and liver steatosis in deoxycorticosterone acetate- (DOCA-) salt induced hypertensive mice model. Male C57BL/6 mice were divided to receive DOCA-salt plus OA-NO2or DOCA-salt plus vehicle and another group received neither DOCA-salt nor OA-NO2(control group). After 3-week treatment with DOCA-salt plus 1% sodium chloride in drinking fluid, the hypertension was noted; however, OA-NO2had no effect on the hypertension. In DOCA-salt treated mice, the plasma triglyceride and total cholesterol levels were significantly increased compared to control mice, and pretreatment with OA-NO2significantly reduced these parameters. Further, the histopathology of liver exhibited more lipid distribution together with more serious micro- and macrovesicular steatosis after DOCA-salt treatment and that was consistent with liver tissue triglyceride and nonesterified fatty acids (NEFA) content. The mice pretreated with OA-NO2showed reduced liver damage accompanied with low liver lipid content. Moreover, the liver TBARS, together with the expressions of gp91phox and p47phox, were parallelly decreased. These findings indicated that OA-NO2had the protective effect on liver injury against DOCA-salt administration and the beneficial effect could be attributed to its antihyperlipidemic activities.

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Insights into the Roles of Gut Microbes in Obesity

Interdisciplinary Perspectives on Infectious Diseases ◽

10.1155/2008/829101 ◽

2008 ◽

Vol 2008 ◽

pp. 1-9 ◽

Cited By ~ 17

Author(s):

Yolanda Sanz ◽

Arlette Santacruz ◽

Giada De Palma

Keyword(s):

Body Weight ◽

Weight Gain ◽

Gut Microbiota ◽

Metabolic Disorders ◽

Cholesterol Metabolism ◽

Body Weight Gain ◽

Inflammatory Factors ◽

Public Health Issue ◽

Low Grade ◽

Gut Microbes

Obesity is a major public health issue as it enhances the risk of suffering several chronic diseases of increasing prevalence. Obesity results from an imbalance between energy intake and expenditure, associated with a chronic low-grade inflammation. Gut microbes are considered to contribute to body weight regulation and related disorders by influencing metabolic and immune host functions. The gut microbiota as a whole improves the host's ability to extract and store energy from the diet leading to body weight gain, while specific commensal microbes seem to exert beneficial effects on bile salt, lipoprotein, and cholesterol metabolism. The gut microbiota and some probiotics also regulate immune functions, protecting the host form infections and chronic inflammation. In contrast, dysbiosis and endotoxaemia may be inflammatory factors responsible for developing insulin resistance and body weight gain. In the light of the link between the gut microbiota, metabolism, and immunity, the use of dietary strategies to modulate microbiota composition is likely to be effective in controlling metabolic disorders. Although so far only a few preclinical and clinical trials have demonstrated the effects of specific gut microbes and prebiotics on biological markers of these disorders, the findings indicate that advances in this field could be of value in the struggle against obesity and its associated-metabolic disorders.

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The Main Anthocyanin Monomer from Lycium ruthenicum Murray Fruit Mediates Obesity via Modulating the Gut Microbiota and Improving the Intestinal Barrier

Foods ◽

10.3390/foods11010098 ◽

2021 ◽

Vol 11 (1) ◽

pp. 98

Author(s):

Peiyun Liu ◽

Wangting Zhou ◽

Weiqi Xu ◽

Yujia Peng ◽

Yamei Yan ◽

...

Keyword(s):

Gut Microbiota ◽

Fecal Microbiota Transplantation ◽

Body Weight Gain ◽

Liver Steatosis ◽

Intestinal Barrier ◽

Fecal Microbiota ◽

Beneficial Effects ◽

Lycium Ruthenicum ◽

First Time ◽

Gut Microbiota Composition

Anthocyanins have been shown to exert certain antiobesity properties, but the specific relationship between anthocyanin-induced beneficial effects and the gut microbiota remains unclear. Petunidin-3-O-[rhamnopyranosyl-(trans-p-coumaroyl)]-5-O-(β-D-glucopyranoside) (P3G) is the main anthocyanin monomer from the fruit of Lycium ruthenicum Murray. Therefore, in this study, we investigated the antiobesity and remodeling effects of P3G on gut microbiota through a high-fat diet (HFD)-induced obesity mouse model and a fecal microbiota transplantation experiment. P3G was found to reduce body weight gain, fat accumulation, and liver steatosis in HFD-induced obese mice. Moreover, supplementation with P3G alleviated the HFD-induced imbalance in gut microbiota composition, and transferring the P3G-regulated gut microbiota to recipient mice provided comparable protection against obesity. This is the first time evidence is provided that P3G has an antiobesity effect by changing the intestinal microbiota. Our present data highlight a link between P3G intervention and enhancement in gut barrier integrity. This may be a promising option for obesity prevention.

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Akkermansia muciniphila improves metabolic profiles by reducing inflammation in chow diet-fed mice

Journal of Molecular Endocrinology ◽

10.1530/jme-16-0054 ◽

2017 ◽

Vol 58 (1) ◽

pp. 1-14 ◽

Cited By ~ 64

Author(s):

Shaoqian Zhao ◽

Wen Liu ◽

Jiqiu Wang ◽

Juan Shi ◽

Yingkai Sun ◽

...

Keyword(s):

Body Weight ◽

Glucose Tolerance ◽

Metabolic Diseases ◽

Body Weight Gain ◽

Inflammatory Factors ◽

Chow Diet ◽

Low Grade ◽

Akkermansia Muciniphila ◽

Inflammatory Status ◽

Underlying Mechanisms

Abnormal shifts in the composition of gut microbiota contribute to the pathogenesis of metabolic diseases, including obesity and type 2 diabetes (T2DM). The crosstalk between gut microbes and the host affects the inflammatory status and glucose tolerance of the individuals, but the underlying mechanisms have not been elucidated completely. In this study, we treated the lean chow diet-fed mice with Akkermansia muciniphila, which is thought to be inversely correlated with inflammation status and body weight in rodents and humans, and we found that A. muciniphila supplementation by daily gavage for five weeks significantly alleviated body weight gain and reduced fat mass. Glucose tolerance and insulin sensitivity were also improved by A. muciniphila supplementation compared with the vehicle. Furthermore, A. muciniphila supplementation reduced gene expression related to fatty acid synthesis and transport in liver and muscle; meanwhile, endoplasmic reticulum (ER) stress in liver and muscle was also alleviated by A. muciniphila. More importantly, A. muciniphila supplementation reduced chronic low-grade inflammation, as reflected by decreased plasma levels of lipopolysaccharide (LPS)-binding protein (LBP) and leptin, as well as inactivated LPS/LBP downstream signaling (e.g. decreased phospho-JNK and increased IKBA expression) in liver and muscle. Moreover, metabolomics profiling in plasma also revealed an increase in anti-inflammatory factors such as α-tocopherol, β-sitosterol and a decrease of representative amino acids. In summary, our study demonstrated that A. muciniphila supplementation relieved metabolic inflammation, providing underlying mechanisms for the interaction of A. muciniphila and host health, pointing to possibilities for metabolic benefits using specific probiotics supplementation in metabolic healthy individuals.

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Akkermansia muciniphila, a New Generation of Beneficial Microbiota in Modulating Obesity: A Systematic Review

Microorganisms ◽

10.3390/microorganisms9051098 ◽

2021 ◽

Vol 9 (5) ◽

pp. 1098

Author(s):

Jumana Nabil Abuqwider ◽

Gianluigi Mauriello ◽

Mohammad Altamimi

Keyword(s):

Systematic Review ◽

Metabolic Disorders ◽

Web Of Science ◽

Controlled Trials ◽

Low Grade ◽

Akkermansia Muciniphila ◽

Randomized Controlled ◽

Treatment Of Obesity ◽

New Generation ◽

Low Grade Inflammation

Obesity is a complex syndrome and is recognized as the ultimate pathway of many chronic diseases. Studies using Akkermansia muciniphila supplementation strategy have proved to be effective for the prevention and treatment of obesity and other metabolic disorders. Although there are studies that support the protective effect of this strategy, the effects on the prevention of obesity on humans are not clear yet and need more investigation. The aim of this study is to investigate the effect of A. muciniphila administration on modulating obesity. This systematic review was generated from articles published within the last 10 years. All articles were in English and included animal subjects. The review relied on the search engines Google Scholar, Pub Med, Web of Science and Medline using the following keywords: A. muciniphila, next-generation probiotic, new-generation probiotic, obesity, fat mass, body fat and lipid profile. The search has revealed 804 articles with relevant key words. After the exclusion of irrelevant articles, 10 studies were selected based on the criteria. These studies were randomized controlled trials that have shown that A. muciniphila modulates obesity by regulating metabolism and energy hemostasis and improving insulin sensitivity and glucose hemostasis. In addition, studies showed this microorganism enhances low grade inflammation by different mechanisms.

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Novel and Practical Approaches to Manage Diet-induced Metabolic Disorders: Part-I

Current Pharmaceutical Design ◽

10.2174/138161282639201110165712 ◽

2020 ◽

Vol 26 (39) ◽

pp. 4953-4954

Author(s):

Mallikarjuna Korivi ◽

Betty Revon Liu

Keyword(s):

Metabolic Disorders ◽

Dietary Habits ◽

Healthy Lifestyle ◽

Modern World ◽

Successful Management ◽

Exercise Interventions ◽

Beneficial Effects ◽

Effective Strategies ◽

Dietary Strategies ◽

Global Health Problem

Metabolic syndrome (MetS) which is caused by poor dietary habits and sedentary behavior is a serious global health problem. MetS is a cluster of risk factors, represented by central obesity, hyperglycemia, dyslipidemia, and hypertension. In the 21st century, MetS and associated comorbidities, including obesity, diabetes and cardiovascular diseases, are the major threats to human health. Practical dietary strategies, nutritional bioactive compounds and a healthy lifestyle are claimed to be efficient in the management of one or more components of MetS. Nevertheless successful management of MetS and commodities is still a major concern. Since hyperglycemia, inflammation and redox imbalance are intrinsically involved in the progression of MetS comorbidities, finding effective strategies that precisely target these systems is highly warranted. In this scenario, pharmacological and non-pharmacological approaches with or without dietary patterns, phytochemicals or exercise interventions are the practical strategies to combat MetS and associated diseases. However, designing and prescribing of optimal nutritional patterns and exercise regimens remains a big challenge to achieve the maximum beneficial effects. This thematic issue addressed the concerns and provided practical strategies to overcome the malady of MetS in the modern world.

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