An In Vitro Model to Investigate the Role of Helicobacter pylori in Type 2 Diabetes, Obesity, Alzheimer’s Disease and Cardiometabolic Disease

Abstract

Helicobacter pylori (Hp) is a Gram-negative bacterium colonizing the human stomach. Nuclear Magnetic Resonance (NMR) analysis of intracellular human gastric carcinoma cells (MKN-28) incubated with the Hp cell filtrate (Hpcf) displays high levels of amino acids, including the branched chain amino acids (BCAA) isoleucine, leucine, and valine. Polymerase chain reaction (PCR) Array Technology shows upregulation of mammalian Target Of Rapamycin Complex 1 (mTORC1), inflammation, and mitochondrial dysfunction. The review of literature indicates that these traits are common to type 2 diabetes, obesity, Alzheimer’s diseases, and cardiometabolic disease. Here, we demonstrate how Hp may modulate these traits. Hp induces high levels of amino acids, which, in turn, activate mTORC1, which is the complex regulating the metabolism of the host. A high level of BCAA and upregulation of mTORC1 are, thus, directly regulated by Hp. Furthermore, Hp modulates inflammation, which is functional to the persistence of chronic infection and the asymptomatic state of the host. Finally, in order to induce autophagy and sustain bacterial colonization of gastric mucosa, the Hp toxin VacA localizes within mitochondria, causing fragmentation of these organelles, depletion of ATP, and oxidative stress. In conclusion, our in vitro disease model replicates the main traits common to the above four diseases and shows how Hp may potentially manipulate them.

Crosstalk between Gut and Brain in Alzheimer’s Disease: The Role of Gut Microbiota Modulation Strategies

“…On the other hand, obesity is also associated with morphological and functional impairment in mitochondria that initiate insulin resistance (responsible for tau hyperphosphorylation and Aβ aggregation) peripheral inflammation, memory deficits, and oxidative stress that increase the risk of AD [ 70 , 71 , 72 ]. Cuomo et al [ 73 ] disclosed that PCR and NMR analyses showed that Helicobacter pylori could potentially modulate AD, type-2 diabetes, cardio-metabolic disease, and obesity. Helicobacter pylori induces high levels of amino acids and activates the mammalian target of rapamycin complex 1 (regulates the host’s metabolism) and branched-chain amino acids.…”

Genetics of Host Protection against Helicobacter pylori Infections

“…This result shows the under-appreciated opportunity offered by metabolomics to reach definitive conclusions when enrolling a small number of patients [ 58 ]. The selective power of metabolomics has been confirmed by an independent study [ 14 ].…”

“…Hp displays several more properties. Grown in the presence of low iron or high salt concentrations, the bacterium rapidly selects the carcinogenic variant FuR88H [ 13 ], which is associated with several non-gastric diseases [ 14 ]. Furthermore, Hp displays conflicting properties: it is the main risk factor for gastric carcinoma and gastric MALT lymphoma [ 7 ], but protects against esophageal adenocarcinoma, Barrett’s esophagus, and gastroesophageal reflux [ 15 ].…”

“…The same traits also characterize type 2 diabetes (T2D), obesity (OB), Alzheimer’s disease (AD), and cardiometabolic disease (CMD) [ 51 , 52 , 53 ]. These results stimulated further work to determine whether Hp has a role in these diseases [ 14 ]. The use of a conventional epidemiological study was excluded since it would have required a very large number of Hp -infected patients and as many controls.…”

“…Intensity of amino acids is expressed in arbitrary units and represented as means ± SD (* p < 0.5; ** p < 0.01; *** p < 0.001) calculated from two experiments, each carried out in quadruplicate (Reprinted with permission from ref. [ 14 ]. Copyright 2021, Domenico Iannelli).…”