The gut microbiome has been identified as a potential factor in weight regulation. Thirty-nine percent of the adults are overweight (25–۲۹.۹ kg/m2) and 13% are obese (BMI≥۳۰kg/m2) worldwide. Recently, it has been found that obesity may affect brain function and structure, as it is associated with impaired cognition and alterations in gray matter (GM) and white matter (WM). Moreover, a higher BMI and waist-to-hip ratio (WHR) have been associated with lower fractional anisotropy (FA) values. Moreover, it is proposed that obesity increases the risk of developing dementia later in life by 60–۹۰%, versus healthy weight individuals. A growing of evidence reveals that obesity is related with alterations in neuroendocrine production and secretion, including ghrelin, insulin, GLP-1 and PYY.
Bariatric surgery for obesity treatment
Bariatric surgery is an effective treatment for obesity leading to rapid and sustainable weight loss. Bariatric surgery decreases body weight not only due to physical effects such as reduced food intake and malabsorption but also due to the various neuroendocrine changes which affect energy homeostasis and hunger/satiety. Moreover, Bariatric surgery might improve the gut microbiota diversity and restore white adipose tissue function, which can improve obesity-related immunological and cognitive impairments. The gut-brain axis consists of a bidirectional communication system, connected through the vague nerve, spinal fibers and sympathetic and parasympathetic fibers which are directly innervating the gastrointestinal tract. These elements communicate through endocrine messengers, neuro-immune mediators and neuroactive metabolites.
Conclusion
To summarize, Bariatric surgery is a good procedure to treat obesity and its related pathologies, however long-term effects remain unsolved. Future research should focus on the long-term effects of Bariatric surgery, to be able to investigate the neuroendocrine, microbiota and white adipose tissue changes and to potentially determine the new “normal” after homeostatic adjustments. Various studies have focused on neuroendocrine alterations already after six months. Six months post-surgery patients lose weight rapidly and generally still follow their post-operative diet. Therefore, the observed effects 6 months post-surgery might differ at longer follow-ups, when patients achieve a stable weight, or regain weight.
Current evidence described gut microbiota dysbiosis is closely linked to obesity. In the treatment of obesity, a holistic approach including diet, pharmacotherapy, physical activity, bariatric surgery, and psychological support is recommended.
Weight-loss diets and gut microbiota
There is strong evidence that the Mediterranean or vegetarian/vegan diets are effective in promoting the optimal diversity and richness in beneficial bacteria. A vegetarian/vegan diet positively alters the gut microbiota through the development of a diverse and stable microbiome and Mediterranean diet is associated with increased levels of SCFAs. A Mediterranean diet has high levels of dietary fiber, n-3 fatty acids and polyphenols, as well as low levels of processed food. Data from research studies indicates that MD positively affects the GM by increasing the abundance of Bacteroidetes,Faecalibacterium prausnitzii, Clostridium (cluster XIVa), Bifidobacteria, and Lactobacilli, while decreasing the abundance of Firmicutes.
Microbiota manipulation and weight loss
The microbial-targeted therapies, including prebiotics, probiotics, and synbiotics, are considered adjuvant in obesity management. However there are different results, mainly because of the great heterogeneity of the studies because of different strains, interventional durations, doses, and forms. It is also unclear whether using these biotics accompanied by dietary intervention or bariatric surgery therapy will be more effective in obesity management in the short and long-term weight-loss maintenance.
The positive effects of lactobacillus probiotics on weight management has been reported. Certain strains of Lactobacillus, such as L. Rhamnosus, L. Plantarum, L. Paracasei, and L. Gasseri, have shown some promising anti-obesity effects. While there is abundant evidence of the effect of supplementation of probiotics treatments, it is also important to acknowledge that not all mentioned studies have shown significant outcomes. This implies that studies with larger sample sizes and longer observation periods are necessary, and more extensive investigation of probiotics supplementation is needed to gain more knowledge. While microbiome-based medicines have made remarkable progress in the last decade from prebiotics and probiotics to live bio therapeutics for the weight management, there are still safety concerns and regulatory issues to be addressed.
Fecal microbiota transplant
The fecal microbiota transplant (FMT) is currently experimental and lacks authorization, posing numerous ethical, legal, and social challenges that must be resolved as part of an effective regulatory policy response. Frozen feces, freeze-dried stool, and more advanced items such as capsules containing synthetic stool generated in culture and assembled are all examples of the wide range of products of FMT treatment. Due to the risks associated with incorrect donor screening and unsatisfactory patient follow-up, any regulatory outcome that restricts access by either reducing supply or significantly increasing the cost of therapy should be implemented with extreme caution.
Next-Generational Probiotics (NGPs)
NGPs are composed of live bacteria and can be used to treat or prevent obesity. While established probiotic and microbiome research facilities can investigate NGPs, commercially motivated start-up biotechnology organizations or pharmaceutical firms are more likely to study Live Bio therapeutic Products.
prepared by:Nazila Kassaian, Marzieh Rahim khorasani
The intestinal microbiota is honored as the key regulator of host homeostasis. The compositional imbalance of microbial communities commonly causes metabolic disorders and exacerbates disease progression. Akkermansia muciniphila (Akk) is a strict anaerobe Gram-negative bacterium which first isolated from human feces in 2004. AKK uses mucin as its sole carbon, nitrogen, and energy source. Akkermansia muciniphila is one of the most abundant single species in the human intestinal microbiota. Since its discovery in 2004, the role of Akk in human metabolic health and disease therapy has been widely studied and therefore it has been called “next-generation beneficial microbes” and“one of the most promising probiotics”. Up to now, many papers associated with Akermansia muciniphila have been published, with diabetes and obesity as the factors under the greatest focus, and cancer as the hot topic of recent research. In the last decade, it was uncovered that Akermansia muciniphila can prevent and ameliorate metabolic syndrome, obesity, diabetes, aging, inflammation, neurodegenerative diseases, and negative effects of cancer therapy. Although it is comprehensively elaborated on the critical functions of Akermansia muciniphila in the metabolism of human health and nutrient utilization, the exhaustive signaling molecular mechanism of Akermansia muciniphila interacting with the host is still not completely understood. Yet, it is worth noting that several studies found that elevated Akk abundance as a paradigm for “next-generation beneficial microorganisms” is positively associated with aggravated host disease progression.
The Cultivation Characteristics of Akkermansia muciniphila
Akk is strictly anaerobic and mainly grown in mucin medium but also can grow on a limited number of sugars including N-acetylgalactosamine, N-acetylglucosamine or a synthetic medium constituted of glucose, peptone, and threonine that has been confirmed to be safe for human administration.
Glucosamine-6-phosphate (GlcN6P) exists in mucin is also necessary for Akk growth, and promoting adaptation to the mucosal niche. Nowadays, the mucin medium is widely and mainly used
to cultivate Akk, but the risk of animal-derived mucins is incompatible with human administration. The cultivation and growth of Akk need strictly anaerobic conditions, which make its mass production more challenging, and it still needs further investigations for improving its cultivation method and safety for human oral administration.
Akkermansia muciniphila in Preventing and Ameliorating Obesity and Metabolic Disorders
Obesity and type2 diabetes are associated with low-grade inflammation and specific changes in gut microbiota composition such as Akk prevalence. In addition to the genome of Akk, the membrane proteins and extracellular vesicles (EVs) of Akk have attracted more attention in the prevention and treatment of obesity and type 2 diabetes. Individuals with obesity have a significantly higher
abundance of Firmicutes, whereas the abundance of Akk is significantly decreased in individuals with obesity and diabetes which is inversely associated with body fat mass and glucose intolerance. The abundance of Akk is strongly correlated with body mass index (BMI) and antidiabetic drug usage. Akk alleviates -induced metabolic disorders, including fat mass gain, metabolic endotoxemia, adipose tissue inflammation, and insulin resistance, as well as increases the intestinal levels of endocannabinoids that regulate inflammation, gut barrier and gut peptide secretion. In high fat diet -induced diabetic mice, EV treatment can improve intestinal barrier integrity by increasing tight junction (TJ) protein expression in an AMP-activated protein kinase -dependent manner. Akk also ameliorates chronic low-grade inflammation by decreasing plasma levels of lipopolysaccharide (LPS)-binding protein (LBP) and leptin and inactivating LPS/LBP downstream signaling mediated.
Conclusions and Future strategies
Critical contributions of Akermansia muciniphila toward metabolic health have begun to be elucidated. In particular, more recent studies is revealing how the effects of Akk extend beyond the GI tract, especially for the so-called gut–brain, gut–liver, gut–bone, gut–heart, gut–adipose and gut–muscle tissue axes, and cancer therapy. To date, the primary focus has been on the use of Akk to ameliorate diabetes, obesity, metabolic diseases, neurodegenerative diseases, inflammation, aging, and the negative effects of cancer therapy. The crucial knowledge gaps remain in this area, specifically on how Akk modulates lipid and glucose metabolism, brain metabolism, and the immune response. However, negative effects of Akk and the safe dose are comparatively less well understood.
Keshavarz Azizi Raftar S, Ashrafian F, Yadegar A, Lari A, Moradi H.R, et al. The Protective Effects of Live and Pasteurized Akkermansia muciniphila and Its Extracellular Vesicles against HFD/CCl4-Induced Liver Injury. Microbiol. Spectr. 2021, 9, e0048421.
Obesity is closely related to the gut microbiota. The active gut microbiota will produce a large number of physiologically active substances, including short-chain fatty acids, vitamins, and health-beneficial products such as anti-inflammatory, analgesic, and antioxidant products, along with potentially harmful products such as neurotoxins, carcinogens, and immunotoxins. These products can enter the blood, directly regulate the expression of genes, and affect human immune and metabolic processes. Therefore, a healthy gut microbiota is essential for maintaining the body’s metabolism and energy balance. An imbalance in the gut microbiota can cause metabolic disorders and increase central appetite, leading to obesity.
Main Results
It is suggested that an increased Firmicutes/Bacteroidetes ratio at the phylum level is an important feature of the gut microbiota in obesity. The family Christensenellaceae and the genera Methanobacteriales, Lactobacillus, Bifidobacteria, and Akkermansia are usually considered as probiotics, and their relative abundance is often inversely associated with obesity. Gut microbiota regulates obesity by regulating energy absorption, central appetite, fat storage, chronic inflammation, and circadian rhythms. The effects of genetic and environmental factors on gut microbiota in obesity are being discussed.
CONCLUSION
Dysbiosis of the gut microbiota has been shown to be closely linked to obesity. Many gut microorganisms have been identified to be related to obesity. They induce the occurrence and development of obesity by increasing host energy absorption, increasing central appetite, enhancing fat storage, contributing to chronic inflammation, and regulating circadian rhythms. Due to the complexity and diversity of the gut microbiota, the mechanism by which the gut microbiota induces obesity still needs to be further studied. Obesity is the result of a combination of genetic and environmental factors. Data analysis based on larger samples to clarify the mechanism of the association between the gut microbiota and obesity, functional group studies of ecological significance to identify potential pathogenic members of the gut microbiota associated with obesity, and specific microbiota management for obese individuals will be the focus of future research.
Overweight and obesity, among the most common diseases in the world, contribute to other pathological conditions including cardiovascular disease, cancer, and metabolic syndrome. Overweight and obesity produce changes in the gut microbiota because of altering intestinal permeability (endo-toxemia), stimulating the endocannabinoid system, and increasing the provision of calories. All these alterations must be considered in a treatment strategy to return a patient to homeostasis. Such strategies have the potential not only of improving the health of individuals, but also of enabling enormous savings in the health care system.
Overweight and Obesity Treatment by gut microbiota alteration
Numerous reports refer to beneficial effects of probiotics in overweight or obese individuals. Indigestible oligosaccharides, inulin, lactulose and resistant starch which act as prebiotics, enhance the amount of probiotics and are effective for weight loss.Synbiotic which is the combination of probiotic and prebiotics, is recommended by the physician attending an overweight or obese patient. The intake of postbiotic and para-probiotics also improves the condition of excess body fat.
Morbid obesity can be treated with intestinal microbiota transplantation at a lower cost and with less morbidity than bypasses. For a patient that has already undergone a bypass, probiotics, prebiotics, or synbiotics along with exercise is recommended to continue to control weight by modulating the intestinal microbiota. Of course, the indications of the FDA must be considered when performing intestinal microbiota transplantation.
Conclusion
Dysbiosis is caused by many factors such as stress, diet, medications, and metabolic disorders. Many studies have found that diet, probiotics, prebiotics, symbionts, intestinal microbiota transplantation, and fecal microbiota transplantation can help overweight and obese patients significantly reduce excess body fat.
