“More Guts Than Brains?”–The Role of Gut Microbiota in Idiopathic Intracranial Hypertension

Abstract

Background:Idiopathic intracranial hypertension syndrome (IIH) is most common among obese women. Weight loss is an important factor in improving papilledema. Over the last decade, growing evidence has identified gut microbiota as a potential factor in the pathophysiology of obesity. Accordingly, we investigated whether the gut microbiome is modified in IIH patients compared with healthy controls, and provide possible new treatment venues.Methods:Shotgun metagenomic sequencing of the gut microbiome of 25 cases of IIH patients (according to the modified Dandy criteria) and 20 healthy controls. Participants were further stratified according to their body mass index. The total DNA from each sample was extracted using the PureLink Microbiome DNA Purification Kit A29789 (Invitrogen, Thermo Fisher Scientific, US). Library preparation was performed using the Nextera DNA Flex Library Prep Kit. Samples were sequenced on the Illumina Novaseq 6000 device. A list of bacterial species that significantly differed between the IIH patients and healthy controls was produced in addition to species diversity. In addition, patients' cohort alone was analyzed, (excluding the healthy controls), and the effect of acetazolamide treatment on their gut microbiota was analyzed.Results:IIH patients have a lower diversity of bacterial species compared with healthy individuals. These bacteria, that is, Lactobacillus ruminis (L. ruminis) (p<6.95E-08), Atopobium parvulum (p<3.9E-03), Megamonas hypermegale (p<5.61E-03), Ruminococcus gnavus (p<1.29E-02), MEL.A1 (p<3.04E-02), and Streptococcus sp. I-G2 (p<3.04E-02), were previously characterized with beneficial health effects. Moreover, we found that Lactobacillus brevis, a beneficial bacterium as well, is more abundant in acetazolamide treated patients (p<7.07E-06).Conclusions:Gut microbiota plays a potential role in IIH etiology and therefore, can provide a promising new treatment approach for this disease.

Dysregulation of Amino Acid, Lipid, and Acylpyruvate Metabolism in Idiopathic Intracranial Hypertension: A Non-targeted Case Control and Longitudinal Metabolomic Study

“…The increase in formylpyruvate in serum could be related to alterations in the gut microbiome, which have recently be shown to be important in IIH development. 30 Notably, other metabolite pathways that were found to be affected in this study have also been shown to be altered by gut microbiota including acyl carnitines, diacylglycerides, and sphingolipids. 31−34 One explanation is that in the disease state, with increased ICP, the transfer of formylpyruvate across the blood−brain barrier appears to be reduced and following therapeutic interventions, and reduction of ICP, transport across the blood−brain barrier recovers and formylpyruvate returns to nearer non-disease levels in CSF and serum.…”

“…The observed relative concentration of formylpyruvate was increased in serum and decreased in CSF when comparing IIH patients to controls, suggesting that this metabolite is synthesized outside the central nervous system (e.g., human systemic tissues or gut microbiome) and then potentially crosses the blood–brain barrier. The increase in formylpyruvate in serum could be related to alterations in the gut microbiome, which have recently be shown to be important in IIH development . Notably, other metabolite pathways that were found to be affected in this study have also been shown to be altered by gut microbiota including acyl carnitines, diacylglycerides, and sphingolipids. − One explanation is that in the disease state, with increased ICP, the transfer of formylpyruvate across the blood–brain barrier appears to be reduced and following therapeutic interventions, and reduction of ICP, transport across the blood–brain barrier recovers and formylpyruvate returns to nearer non-disease levels in CSF and serum.…”

Prospects for Leveraging the Microbiota as Medicine for Hypertension

“…A link between archaea and cardiovascular health has also been proposed, highlighting the need for a more comprehensive understanding of biota interactions that may regulate cardiovascular function. 98 Beyond the gut, the mouth harbors the oral microbiota, which may play a role in BP regulation. Recent research suggests links between specific oral bacteria and systolic BP, diastolic BP, and hypertension prevalence.…”

“…A link between archaea and cardiovascular health has also been proposed, highlighting the need for a more comprehensive understanding of biota interactions that may regulate cardiovascular function. 98…”