Obesity, a multifaceted syndrome recognized as a significant public health concern in the 21st century, is often the root cause of many chronic diseases. Characterized by an imbalance between energy consumption and expenditure, leading to weight gain and adiposity, obesity affects over 671 million people worldwide as of 2016. The prevalence of obesity has tripled between 1975 and 2016, with rural areas experiencing the most dramatic increases, mainly due to overconsumption of animal products, refined grains, and added sugars. Gut microbes play a pivotal role in regulating host metabolism. Among these, Akkermansia muciniphila has emerged as a promising candidate for modulating obesity and related metabolic disorders.
The Gut Microbiota and Obesity
The human intestine hosts tens of trillions of microorganisms, including over 1000 different species of bacteria with at least 3 million genes. The composition and distribution of gut microbiota vary across different anatomical sites of the intestine and are influenced by lifestyle, diet, and health status. The colon is the most densely populated site, with Clostridium Type IV and XIV, Bacteroidetes, Bifidobacterium, and Enterobacteriaceae being the predominant inhabitants.
The gut microbiota's composition is strongly associated with obesity and metabolic syndrome. The ratio of Firmicutes to Bacteroides, in particular, has been identified as a crucial factor, with an increased ratio observed in adults with higher BMI. Mucin, a protective barrier against xenobiotics in the intestine, plays a vital role in microbiota adhesion to the intestinal layers. Bacteria capable of degrading mucin are better equipped to survive in the dynamic intestinal microenvironment.
Akkermansia Muciniphila: A Next-Generation Probiotic
Akkermansia muciniphila is an early colonizer of the intestinal tract, typically present at concentrations of 108 cells/gram or more, accounting for over 1% of total fecal microbes. This bacterium can utilize mucin as its sole source of carbon and nitrogen. It is considered a "next-generation probiotic," and its significance has been increasingly recognized since its initial isolation in 2004. As the only member of the Verrucomicrobia phylum in the mammalian gut, it is easily detectable using 16S rRNA gene sequencing.
Numerous studies have demonstrated a correlation between the abundance of Akkermansia in the gut and the host's health and disease status. Its numbers tend to decrease with aging, highlighting its potential role in maintaining health. Akkermansia muciniphila has been shown to modulate the endocannabinoid (eCB) system, an essential regulatory system involved in glucose and energy metabolism, relevant in the context of obesity, type 2 diabetes, and inflammation.
Read also: Weight Loss Guide Andalusia, AL
Investigating the Impact of A. muciniphila on Obesity
Studies using Akkermansia muciniphila supplementation have shown effectiveness in preventing and treating obesity and other metabolic disorders. Human and animal trials have indicated a positive correlation between A. muciniphila intervention and improvements in obesity and metabolic disorders. Supplementation with A. muciniphila, along with strategies to increase its abundance in the gut microbiota, may offer a novel approach to managing obesity.
Methodology of Studies
A systematic review of clinical trials and controlled interventional studies was conducted to evaluate the role of A. muciniphila in obesity and lipid parameters in both obese and non-obese populations. The review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines (PRISMA 2009). The search included articles published within the last 10 years, focusing on animal subjects and written in English. Databases such as Google Scholar, PubMed, Web of Science, and Medline were searched using keywords like A. muciniphila, next-generation probiotic, new-generation probiotic, obesity, fat mass, body fat, and lipid profile.
The initial search yielded 804 articles, which were then filtered to exclude irrelevant studies. Ten randomized controlled trials were selected based on criteria such as the use of animal models, the inclusion of a control group, and treatment or intervention with A. muciniphila supplementation. Studies lacking original data, comparison interventions, or those involving human subjects or animals with pathologies were excluded. Data extracted from each article included the author, publication year, sample size, animal species, study design, duration and dose of A. muciniphila ingestion, control details, and outcomes related to obesity and metabolic syndrome. The Modified Downs and Black checklist was used to assess the quality and risk of bias in the studies.
Key Findings from Animal Studies
Ten studies investigated the effect of A. muciniphila supplementation on obesity parameters and metabolic disorders in C57BL/6J mice models.
Yang et al. found that mice fed a high-fat diet (HFD) experienced significant reductions in body weight gain, caloric intake, mesenteric fat weight, subcutaneous fat weight, epididymal fat weight, total fat, and energy efficiency after treatment with a pasteurized culture of A. muciniphila. The study also examined the effects of bacterial supplementation on the colonic gene expression of Glucagon-like peptide-1 (GLP-1) and Peptide YY (PYY), intestinal hormones known for their appetite-suppressing, anti-diabetic, and anti-obesity properties. The treatment with A. muciniphila increased the expression of GLP-1 and PYY, particularly in the colon.
Read also: Beef jerky: A high-protein option for shedding pounds?
Everard et al. compared the effects of viable A. muciniphila administration with heat-killed A. muciniphila. Viable A. muciniphila normalized metabolic endotoxemia, fat storage, adipose tissue metabolism, and the CD11c adipose tissue marker, all of which were induced by diet. The treatment also decreased body weight and improved body composition without altering food intake. These beneficial effects were not observed with heat-killed A. muciniphila.
Other trials observed that pasteurized A. muciniphila significantly decreased body weight gain, total adiposity index, and fat mass gain without affecting accumulated food intake in HFD-fed groups. Additionally, the fecal caloric content significantly increased. Depommier et al. reported that five weeks of supplementation with A. muciniphila at a dosage of 108 CFU decreased body weight gain and significantly reduced fat mass while increasing lean mass in mice fed a normal diet (ND). Visceral fat weight, closely linked to insulin resistance pathogenesis, was also reduced.
Plovier et al. found that daily treatment with 2 × 108 CFU of A. muciniphila live cells reduced HFD-induced weight gain and fat mass gain by approximately 40-50%. Notably, pasteurized A. muciniphila had a greater effect than unpasteurized culture, regardless of food consumption. Mice treated with pasteurized A. muciniphila exhibited normalized mean adipocyte diameter and significantly lower plasma leptin levels compared to control HFD-fed mice. The same study revealed that mice fed with pasteurized A. muciniphila had a higher fecal caloric content, implying reduced caloric absorption, which likely contributed to the observed body weight decrease and fat mass gain.
Wu et al. demonstrated that A. muciniphila GP01 treatment reduced food intake and body weight in both HFD and ND groups. Ashrafian et al. reported that obese mice treated with A. muciniphila-derived extracellular vehicles (EVs) showed a substantial reduction in food consumption and a low level of body weight gain. Both live cells and EVs significantly reduced adipocyte size in HFD-fed mice, with EVs showing more observable results.
However, not all studies reported positive results. Kim et al. and Deng et al. found no significant difference in weight gain between groups treated and non-treated with A. muciniphila. Deng et al. did observe that A. muciniphila treatment alleviated the whitening of brown adipose tissue (BAT) caused by HFD, decreasing the amount of unilocular adipocytes in HFD mice.
Read also: Inspiring Health Transformation
Impact on Glucose Metabolism and Insulin Sensitivity
Yang et al. found that the fasting blood glucose level was significantly higher in the HFD group compared to the normal fed group. However, treatment with A. muciniphila substantially reduced this parameter. The HFD group treated with A. muciniphila significantly reduced the levels of OGTT AUC, serum insulin level, HOMA-IR, and hepatic gene expression of G6Pase. These results indicate that A. muciniphila significantly improves insulin sensitivity and glucose homeostasis.
Human Studies and Population-Scale Investigations
A study based on the American Gut Project (AGP) database of 10,534 subjects investigated the relationship between Akkermansia and obesity risk, adjusting for factors such as age, sex, smoking, alcohol consumption, diet, and country. The median abundance of Akkermansia was 0.08%, and the prevalence of obesity was 11.03%. A nonlinear association was detected between Akkermansia and obesity risk. Higher abundance of Akkermansia was associated with a lower risk of obesity, independent of common confounders.
Potential Harms and Considerations
While Akkermansia muciniphila shows promise as a therapeutic agent, it is essential to consider potential harms and limitations. In specific intestinal microenvironments, excessive enrichment of Akkermansia may not be beneficial.
Conditions like inflammatory bowel disease (IBD), Salmonella typhimurium infection, or post-antibiotic reconstitution may not benefit from Akkermansia supplementation. In the case of Salmonella typhimurium infection, the procolonization of Akkermansia can make Salmonella a dominant bacterium of microbiota. In IBD, where the gut barrier function is already compromised, a mucin-degrading probiotic may exacerbate the condition.
Additionally, caution is warranted in patients with endocrine and gynecological disorders, such as polycystic ovary syndrome (PCOS) or endometriosis, who have a higher risk of developing IBD. These patients may also suffer from dysbiosis of the gut microbiota with chronic intestinal inflammation, which can increase their risk of developing IBD.
Recent findings from the neurologic field indicate a cautionary use of Akkermansia in patients suffering from Parkinson’s disease (PD) or multiple sclerosis (MS). Different studies revealed an increase in Akkermansia abundance in these patients.
Another crucial aspect to consider is Akkermansia's evolutionary potential to acquire antimicrobial resistance genes (ARGs) under antibiotic selective pressure. The evaluation of the antimicrobial susceptibility of Akkermansia is fundamental to meet the safety recommendations of EFSA, especially with its introduction into the food chain.
tags: #akkermansia #muciniphila #weight #loss #study