Probiotics and its Influence on AMPK-Dependent Health Activities

The Role of Probiotics and AMPK in Metabolic Health

Gut microbiota (GM) is influential in maintaining health, and probiotics play a crucial role in this context. The key aspect here is energy homeostasis that refers to the energy metabolism that involves lipid uptake, synthesis, clearance, hydrolysis, and secretion in the liver, adipose tissue, and skeletal muscle. Moreover, the energy status and its control in the cell are regulated by the AMP-activated protein kinase (AMPK), activated by a low rate of ATP/AMP. Due to its integral features, the AMPK complex plays a key role in cell proliferation regulation, cell growth, cell polarity, autophagy, and metabolism. Furthermore, it's activation is shown to prevent cell stress-associated senescence and aging. However, when there is an imbalance in the metabolism of fats, this can contribute to conditions like obesity, metabolic syndrome, and type 2 diabetes mellitus (T2D), often mediated by oxidative stress-related chronic inflammation.

Molecular Mechanisms of Probiotic Influence

Regarding the GM, probiotics such as Clostridium butyricum, a typical resident of healthy mammal guts, can release compounds to increase or restore AMPK activity. Its strain is a known probiotic due to its ability to produce butyrate, a fatty acid that improves intestinal inflammatory disorders via an AMPK-dependent process, resulting in decreased lipogenesis, oxidative stress, and increased lipid oxidation.

Among probiotics, the Bifidobacterium genus has several promising members known to aid in reducing weight gain, inflammation, enhancing immune responses, and more. Mechanistically, Bifidobacterium function via the inactivation of the pro-inflammatory cytokines TNF-α and NF-κB, which helps mitigate the damage that lipopolysaccharides (LPS) and alcohol may cause to the gut and liver.

The Lactobacillus genre, often used in commercial probiotics supplements, has also shown properties beneficial to gut health via pathways related to the inhibition of NF-κB, LPS, and TNF-α, and activation of SIRT-1, all mediated by AMPK activation.

Akkermansia muciniphila and AMPK

The beneficial effect of A. muciniphila occurred through contacting Toll-like receptor 2 (TLR2) on intestinal epithelial cells by wall components. The live and pasteurized Akkermansia muciniphila strains can prevent LPS-induced epithelial barrier dysfunction and inflammatory response in Caco-2 monolayers through activating AMPK and inhibiting NF-κB. These findings provide a theoretical basis for understanding the mechanisms and application of pasteurized Akkermansia muciniphila for disease pre-protection.

Fig.1 Pretreatment with live and pasteurized A. muciniphila can attenuate intestinal barrier dysfunction in LPS-induced Caco-2 cells. ¹

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Reference

1. Shi, Mengxuan, et al. "Pasteurized Akkermansia muciniphila ameliorate the LPS-induced intestinal barrier dysfunction via modulating AMPK and NF-κB through TLR2 in Caco-2 cells." Nutrients 14.4 (2022): 764. Distributed Under Open Access license CC BY 4.0, without modification.

For Research Use Only. Not intended for use in food manufacturing or medical procedures (diagnostics or therapeutics). Do Not Use in Humans.