Akkermansia muciniphila, a mucin-degrading bacterium commonly found in the human gut, has garnered significant attention in recent years due to its promising probiotic activities against obesity and diabetes. This article delves into the multifaceted relationship between A. muciniphila and weight loss, exploring its mechanisms of action, dietary strategies to enhance its abundance, and potential implications for various health conditions.
Introduction
Obesity, a complex syndrome resulting from an imbalance between energy consumption and expenditure, has become a major public health concern in the 21st century. Characterized by excessive weight gain and adiposity, obesity is associated with a range of chronic diseases, including cardiovascular disorders, type 2 diabetes, and certain cancers. Gut microbes, including bacteria like Akkermansia muciniphila, play a crucial role in regulating host metabolism and energy homeostasis.
What is Akkermansia muciniphila?
Akkermansia muciniphila is a bacterium belonging to the phylum Verrucomicrobia. First isolated and identified in 2004, A. muciniphila utilizes mucin as its primary carbon source. It typically constitutes 3-5% of the human gut microbial community and is also found in various other species. A. muciniphila's mucin-degrading capability provides it with an ecological advantage, particularly when other dietary sources are scarce.
The Link Between A. muciniphila and Metabolic Health
Studies have shown that A. muciniphila is more abundant in the guts of healthy individuals compared to those with diabetes, obesity, bowel diseases, or metabolic disorders. Intervention studies have confirmed an inverse correlation between A. muciniphila abundance and body weight, inflammation, metabolic syndrome, and type 1 and type 2 diabetes.
A. muciniphila supplementation has shown promise in restoring mucus thickness in obese and type 2 diabetic mice, reducing serum lipopolysaccharides (LPS), and improving metabolic profiles. LPS, a component of gram-negative bacteria, indicates gut permeability when present in circulation, suggesting a disruption of the intestinal mucus.
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How Does A. muciniphila Promote Gut Health?
The exact mechanisms by which A. muciniphila exerts its beneficial effects are still under investigation. However, its positive modulation of mucus thickness and gut barrier integrity appears to be key.
The intestinal mucus, synthesized and secreted by goblet cells, consists of two layers: an inner, bacteria-free layer and an outer layer with commensal bacteria. Mucins, the major components of mucus, serve as nutrients for A. muciniphila. Despite its mucin-degrading activity, A. muciniphila is associated with increased mucus thickness and improved intestinal barrier integrity. One possible explanation is that A. muciniphila stimulates mucus turnover by producing short-chain fatty acids (SCFAs) from degraded mucin, which serve as energy sources for the host epithelium responsible for mucin synthesis and secretion.
Dietary Strategies to Enhance A. muciniphila Abundance
Supplementation with Viable A. muciniphila
Although human studies on direct dietary supplementation with A. muciniphila are limited, animal studies have demonstrated a significant increase in A. muciniphila in the gut and/or feces of mice. Supplementation with A. muciniphila has been shown to restore its abundance in mice fed a Western high-fat diet, reduce atherosclerotic plaques, and ameliorate aortic and systemic inflammation.
Supplementation with Selected Probiotics
Animal studies have found that oral administration of a mixture of Lactobacillus rhamnosus LMG S-28148 and Bifidobacterium animalis subsp. lactis LMG P-28149 increased A. muciniphila abundance in high-fat-fed mice. The effectiveness of this probiotic mix was comparable to direct A. muciniphila supplementation. B. animalis subsp. lactis LMG P-28149 appears to be the primary driver of this effect, possibly through the increased production of SCFAs, which promote mucin growth.
Supplementation with Prebiotics
Animal studies have consistently shown that oral administration of fructo-oligosaccharides (FOS), a common prebiotic, promotes the growth of A. muciniphila in various animal models. FOS supplementation has been shown to restore A. muciniphila levels in mice fed a high-fat diet and significantly increase its abundance in ob/ob mice.
Read also: Exploring Akkermansia Muciniphila
A. muciniphila and Weight Loss: Evidence from Animal Studies
Ten studies investigated the effect of A. muciniphila supplementation on obesity parameters and metabolic disorders in C57BL/6J mice. These studies revealed that treatment with pasteurized A. muciniphila decreased body weight gain, caloric intake, and fat weight in high-fat diet (HFD)-fed mice. In addition, pasteurized A. muciniphila increased the colonic gene expression of Glucagon-like peptide-1 (GLP-1) and Peptide YY (PYY), intestinal hormones that suppress appetite and possess anti-diabetic and anti-obesity properties.
Viable A. muciniphila normalized metabolic endotoxemia caused by diet, fat storage, adipose tissue metabolism, and CD11c adipose tissue marker. A. muciniphila treatment decreased body weight and improved body composition without changes of food intake.
Furthermore, pasteurized A. muciniphila decreased body weight gain, total adiposity index, and fat mass gain, while increasing fecal caloric content. Visceral fat weight, closely related to insulin resistance pathogenesis, was also reduced.
Daily treatment with A. muciniphila live cells reduced HFD-induced weight gain and fat mass gain. Mice fed with pasteurized A. muciniphila had a higher fecal caloric content, indicating that pasteurized culture administration reduces caloric absorption.
Treatment with Amuc_1100*, the outer membrane protein of *A. muciniphila* produced in E. coli, resulted in lower body weight and fat mass gain in HFD-fed mice. A. muciniphila GP01 treatment reduced food intake and body weight in both HFD and normal diet (ND) groups.
Read also: Exploring Akkermansia Muciniphila for Weight Loss
Obese mice treated with A. muciniphila-derived extracellular vehicles (EVs) demonstrated a substantial reduction in food consumption and body weight gain. Both live cells and EVs significantly reduced adipocyte size in HFD-fed mice.
However, some studies reported no difference in weight gain between groups treated and non-treated with A. muciniphila. Treatment with cells of strains GP01 and GP25 alleviated the increase in adipocyte size caused by HFD. A. muciniphila treatment also decreased the amount of unilocular adipocytes in HFD mice, alleviating the whitening of brown adipose tissue (BAT).
A. muciniphila and Glucose Metabolism: Evidence from Animal Studies
In HFD groups, fasting blood glucose levels were significantly higher than in normal fed groups. Treatment with A. muciniphila substantially depleted this fasting blood glucose level.
In HFD groups, the oral glucose tolerance test (OGTT) area under the curve (AUC), serum insulin level, homeostatic model assessment for Insulin Resistance (HOMA-IR), and hepatic gene expression of G6Pase were significantly higher than in the normal group. The HFD group treated with A. muciniphila significantly reduced the levels of these four parameters. A. muciniphila significantly increased the hepatic gene expression of glucokinase (GCK), an enzyme involved in glucose utilization.
A. muciniphila and Lipid Metabolism: Evidence from Animal Studies
In HFD groups, serum triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels were significantly higher than in the normal group. The HFD group treated with A. muciniphila significantly reduced the levels of these three parameters. The levels of high-density lipoprotein cholesterol (HDL-C) were significantly lower in the HFD group than in the normal group, but A. muciniphila treatment significantly increased HDL-C levels.
Furthermore, A. muciniphila treatment significantly reduced the hepatic gene expression of sterol regulatory element-binding protein-1c (SREBP-1c), fatty acid synthase (FAS), and stearoyl-CoA desaturase-1 (SCD-1). The hepatic gene expression of peroxisome proliferator-activated receptor α (PPARα) was significantly lower in the HFD group than in the normal group, but A. muciniphila treatment significantly increased PPARα levels.
A. muciniphila and Gut Microbiota: Evidence from Population-Scale Study
A population-scale study based on the American Gut Project (AGP) database of 10,534 subjects revealed that higher abundance of Akkermansia was associated with lower risk of obesity, independent of common confounders such as age, sex, smoking, alcohol drinking, diet, and country. The Akkermansia-obesity association was significantly nonlinear, with a consistent trend toward lower obesity risk for higher Akkermansia abundance.
Potential Harms and Considerations
While A. muciniphila exhibits beneficial effects on the metabolic profile, its abundance may not always induce clinical metabolic improvement. In some cases, orally supplementing Akkermansia may not have the expected effects on intestinal health and clinical conditions.
In Salmonella typhimurium infection, the procolonization of Akkermansia can make Salmonella a dominant bacterium of microbiota. In inflammatory bowel disease (IBD), a mucin-degrading probiotic may not be the appropriate choice, as it can exacerbate colitis.
The use of Akkermansia needs proper attention in patients with endocrine and gynecological disorders such as polycystic ovary syndrome (PCOS) or endometriosis, who may also suffer from dysbiosis of the gut microbiota with chronic intestinal inflammation, exposing them to a higher risk of developing IBD.
The excessive enrichment of Akkermansia may alter the process of mucin degradation, thus impairing the intestinal barrier and inducing the secretion of inflammatory cytokines. In the post-antibiotic reconstitution of the microbial community, Akkermansia replenishment can exacerbate intestinal barrier damage and increase colonic and systemic inflammation.
Elevated abundance of Akkermansia has been observed in patients suffering from Parkinson’s disease (PD) and multiple sclerosis (MS), suggesting a cautionary use of this probiotic in these populations.
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