The choroid plexus epithelium as a novel player in the stomach-brain axis during Helicobacter infection

Abstract

Several studies suggest a link between shifts in gut microbiota and neurological disorders. Recently, we reported a high prevalence of Helicobacter suis (H. suis) in patients with Parkinson's disease. Here, we evaluated the effect of gastric H. suis infection on the brain in mice. One month of infection with H. suis resulted in increased brain inflammation, reflected in activation of microglia and cognitive decline. Additionally, we detected choroid plexus inflammation and disruption of the epithelial blood-cerebrospinal fluid (CSF) barrier upon H. suis infection, while the endothelial blood-brain barrier (BBB) remained functional. These changes were accompanied by leakage of the gastrointestinal barrier and low-grade systemic inflammation, suggesting that H. suis-evoked gastrointestinal permeability and subsequent peripheral inflammation induces changes in brain homeostasis via changes in blood-CSF barrier integrity. In conclusion, this study shows for the first time that H. suis infection induces inflammation in the brain associated with cognitive decline and that the choroid plexus is a novel player in the stomach-brain axis.

Age-Associated Changes in the Immune System and Blood–Brain Barrier Functions

“…Although altered BBB functions were not examined in this study, future works could further elucidate relationships of BBB dysfunction and aging with microbiome alterations. However, we also acknowledge that other plausible neuroimmune mechanisms, such as altered gut-to-brain signals as mediated by the vagus nerve or the BSCFB, could also be contributing to CNS changes caused by gut microbiome dyshomeostasis [152,153].…”

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

“…Infection with H. suis in pigs and mice is associated with increased inflammation in the stomach, characterized by the higher expression of IL-8, -10, -1b, and -4, keratinocyte chemoattractant (KC), lipopolysaccharide-induced CXC chemokine (LIX), and macrophage inflammatory protein (MIP2) depending on the host (72,(76)(77)(78). This leads to the infiltration of B-and T-cells and macrophages in mice, inducing a Th2 response.…”

Modern approaches to investigating non‐neuronal aspects of Alzheimer's disease

“…Under physiologic settings, the CNS is largely protected from serum components by the blood-brain and blood-cerebrospinal fluid barriers, which also provide a largely impenetrable barrier to peripherally administered pharmacotherapeutics [for review, see (54)(55)(56)]. These barriers can become increasingly permeable to larger serum proteins following trauma, and in some diseases (57)(58)(59) [for review, see also (60,61)], the use of serum in CNS cell cultures changes their baseline morphology and transcriptome (16,42,(62)(63)(64). These cultures have been incredibly valuable for investigations of glial cell function (35)(36)(37)(38)52); however, with already highly expressed, disease-reactive transcripts in "baseline" cultures (15,16,18), it is likely that many false-negative results are achieved, as the baseline expression of many known reactive transcripts is so high (Fig.…”