Effects of Live and Pasteurized Forms of Akkermansia from the Human Gut on Obesity and Metabolic Dysregulation

Abstract

Akkermansia muciniphila (A. muciniphila) is a promising probiotic candidate owing to its health-promoting properties. A previous study reported that the pasteurized form of A. muciniphila strains isolated from human stool samples had a beneficial impact on high-fat diet-induced obese mice. On the other hand, the differences in the probiotic effects between live and pasteurized A. muciniphila on the metabolism and immune system of the host are still inconclusive. This study examines the differences between the live and pasteurized forms of A. muciniphila strains on the lipid and glucose metabolism and on regulating the inflammatory immune responses using a HFD-fed obese mouse model. The animals were administered the live and pasteurized forms of two A. muciniphila strains five times per week for the entire study period of 12 weeks. Both forms of the bacterial strains improved the HFD-induced obesity and metabolic dysregulation in the mice by preventing body-weight gains after one week. In addition, they cause a decrease in the weights of the major adipose tissues, adipogenesis/lipogenesis and serum TC levels, improvement in glucose homeostasis and suppression of inflammatory insults. Furthermore, these treatments restored the damaged gut architecture and integrity and improved the hepatic structure and function in HFD-induced animals. On the other hand, for both bacterial strains, the pasteurized form was more potent in improving glucose tolerance than the live form. Moreover, specific A. muciniphila preparations with either live or pasteurized bacteria decreased the number and population (%) of splenic Treg cells (CD4+ Foxp3+) significantly in the HFD-fed animals, further supporting the anti-inflammatory properties of these bacteria.

Akkermansia muciniphila and Gut Immune System: A Good Friendship That Attenuates Inflammatory Bowel Disease, Obesity, and Diabetes

“…Interestingly, several studies have indicated that the outer membrane compounds of A. muciniphila , or pasteurized bacteria, have greater therapeutic potential for metabolic, inflammatory, and autoimmune diseases than live A. muciniphila ( 36 – 38 ). Notably, Kang et al.…”

“…In a murine model of obesity induced by HFD, it was demonstrated that treatment with A. muciniphila 10 8 –10 9 Colony-forming unit (CFU)/mL was able to reduce body weight gain, the accumulation of white adipose tissue (WAT), and energy efficiency and improve liver function impaired by HFD in mice ( Figure 1 ) ( 51 , 52 ). Furthermore, it was reported in the HFD-induced obesity model that the pasteurized form or AmOMV has been successful in reducing or preventing hepatic steatosis and adipogenesis/lipogenesis ( 38 , 53 ). In addition, the increase in Akkermansia ssp.…”

“…Interestingly, several studies have indicated that the outer membrane compounds of A. muciniphila, or pasteurized bacteria, have greater therapeutic potential for metabolic, inflammatory, and autoimmune diseases than live A. muciniphila (36)(37)(38). Notably, Kang et al (2013) reported a change in the composition of EVs in the feces of mice with DSS-induced UC, such as a decrease in the EVs of A. muciniphila and Bacteroides acidifaciens.…”

Probiotic-Based Intervention in the Treatment of Ulcerative Colitis: Conventional and New Approaches

“…A. muciniphila seems to be an irreplaceable member of healthy and balanced gut microbiota; furthermore, it alleviates mucosal inflammation either via microbe–host interactions associated with improved gut barrier function and reduction of inflammatory cytokines, or by improving the microbial community in UC. It is noteworthy that the beneficial effect of A. muciniphila was confirmed for both live and pasteurized forms used in different diseases, including liver injury [ 114 ], obesity, and diabetes 2 [ 115 , 116 , 117 ]. Ottman et al [ 118 ] identified a highly abundant outer membrane pili-like protein, Amuc-100, of A. muciniphila MucT, which through the activation of TLR-2 and TLR-4 induces the production of the regulatory cytokine IL-10 and could be directly responsible for the anti-inflammatory properties of the bacterium.…”

Precise strategies for selecting probiotic bacteria in treatment of intestinal bacterial dysfunctional diseases

“…Most of these effects were linked to the high capacity of this strain to produce metabolites with anti-inflammatory effects. Clostridium butyricum is another potential non-traditional candidate probiotic that can produce metabolites with anti-inflammatory effects, such as butyrate ( 30 , 107 ).…”