Helicobacter and the Potential Role in Neurological Disorders: There Is More Than Helicobacter pylori

Abstract

Trillions of symbiotic microbial cells colonize our body, of which the larger part is present in the human gut. These microbes play an essential role in our health and a shift in the microbiome is linked to several diseases. Recent studies also suggest a link between changes in gut microbiota and neurological disorders. Gut microbiota can communicate with the brain via several routes, together called the microbiome-gut-brain axis: the neuronal route, the endocrine route, the metabolic route and the immunological route. Helicobacter is a genus of Gram-negative bacteria colonizing the stomach, intestine and liver. Several papers show the role of H. pylori in the development and progression of neurological disorders, while hardly anything is known about other Helicobacter species and the brain. We recently reported a high prevalence of H. suis in patients with Parkinson's disease and showed an effect of a gastric H. suis infection on the mouse brain homeostasis. Here, we discuss the potential role of H. suis in neurological disorders and how it may affect the brain via the microbiome-gut-brain axis.

Keywords: Helicobacter pylori; Helicobacter suis; gut microbiota; microbiome–gut–brain axis; neurological disorders.

Figure 1

Changes at the microbiome–gut–brain axis during Helicobacter pylori and Non-H. pylori Helicobacter (NHPH) infection. (A) H. pylori is associated with persistent local inflammation, which might lead to systemic inflammation, characterized by increased levels of free radicals, cytokines and chemokines in the blood. Infection also leads to the release of several neurotransmitters, such as acetylcholine, adrenaline, noradrenaline and dopamine, but also increased levels of neuropeptides, such as vasoactive intestinal peptide (VIP) and c-fos. Moreover, H. pylori can lead to blood–brain barrier breakdown and axonal/neuronal damage. (B) H. suis is associated with inflammation of the stomach, associated with loss of the gastrointestinal barrier function, leading to leakage of TLR4 ligands into the blood. This leads to the breakdown of the blood-CSF barrier, combined with microgliosis and cognitive decline. H. suis-induced changes in the pH possibly leads to changes in the gastrointestinal microbiome. Moreover, lower levels of glutamate are present, which could influence the production of several neurotransmitters. Higher levels of IL-17 can block hippocampal neurogenesis while IFN-γ and lymphotoxins could lead to demyelination. BBB, blood–brain barrier; CSF, cerebrospinal fluid; IL, interleukin; IFN, interferon.