Modulation of the PI3K/Akt/mTOR signaling pathway by probiotics as a fruitful target for orchestrating the immune response

Abstract

The mammalian target of rapamycin (mTOR) and the phosphatidylinositol-3-kinase (PI3K)/protein kinase B or Akt (PKB/Akt) signaling pathways are considered as two but somewhat interconnected significant immune pathways which play complex roles in a variety of physiological processes as well as pathological conditions. Aberrant activation of PI3K/Akt/mTOR signaling pathways has been reported to be associated in a wide variety of human diseases. Over the past few years, growing evidence in in vitro and in vivo models suggest that this sophisticated and subtle cascade mediates the orchestration of the immune response in health and disease through exposure to probiotics. An expanding body of literature has highlighted the contribution of probiotics and PI3K/Akt/mTOR signaling pathways in gastrointestinal disorders, metabolic syndrome, skin diseases, allergy, salmonella infection, and aging. However, longitudinal human studies are possibly required to verify more conclusively whether the investigational tools used to understand the regulation of these pathways might provide effective approaches in the prevention and treatment of various disorders. In this Review, we summarize the experimental evidence from recent peer-reviewed studies and provide a brief overview of the causal relationship between the effects of probiotics and their metabolites on the components of PI3K/Akt/mTOR signaling pathways and human disease.

Diagnostic, Prognostic, and Therapeutic Roles of Gut Microbiota in COVID-19: A Comprehensive Systematic Review

“…are well known for their immunomodulatory effects especially on Th17 and in the amelioration of inflammatory process (de Vrese et al, 2005;Wang et al, 2011;Groeger et al, 2013;Jungersen et al, 2014;King et al, 2014;Han et al, 2016;Schiavi et al, 2016;Bozkurt et al, 2019;Bozkurt and Kara, 2020;Tian et al, 2020;Arenas-Padilla et al, 2021;Chen and Vitetta, 2021;Hong et al, 2021;Milner et al, 2021). Bifidobacterium may be considered as a supplemental therapeutic agent for controlling cytokine storm and inflammation in patients with COVID-19 (Bozkurt and Quigley, 2020;Bozkurt and Quigley, 2020a;Schett et al, 2020;Bhushan et al, 2021Gautier et al, 2021Mohseni et al, 2021).…”

A Live Probiotic Vaccine Prototype Based on Conserved Influenza a Virus Antigens Protect Mice against Lethal Influenza Virus Infection

“…Immunization through the mucous membrane is one of the needle-free approaches that provide significant prophylactic and therapeutic effects due to the induction of a secretory and cellular immune response [ 23 , 24 ]. When probiotic bacteria enter the body by the oral route, they can propagate in the digestive tract and provide beneficial effects for the host [ 25 , 26 ].…”

Molecular and Cellular Mechanisms Influenced by Postbiotics

“…PI3K/AKT modulates cell survival, apoptosis, and intestinal integrity, e.g., mucin production [113]. This pathway may cooperate with NF-κB and MAPK cascades modulating immune responses toward probiotic/postbiotic compounds [114][115][116][117]. The PI3K/AKT pathway is also interconnected with the AMP-activated kinase (AMPK) pathway, a metabolic pathway, which is another cellular effector of probiotics/postbiotics [118][119][120].…”

“…TLR2/TLR6 may attenuate inflammatory/regulatory responses, whereas the TLR2/TLR1 complex may exert pro-inflammatory effects [113][114][115]; however, overall immune responses are still under discussion. Both TLR2/6 ligands [116,117] and TLR2/1 ligands [118] can induce opposing immune responses via these heterodimers. The key explanation for the broad diversity of observed results is probably a time-dependent structure-activity relationship between ligands and TLRs.…”