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.

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Reversible genomic DNA-inversions control expression of numerous bacterial molecules in the human gut, but how this relates to disease remains uncertain. By analyzing metagenomic samples from six human Inflammatory Bowel Disease (IBD) cohorts combined with mice experimentation, we identified multiple invertible regions in which a particular orientation was correlated with disease. These include the promoter of the anti-inflammatory polysaccharide-A (PSA) ofBacteroides fragilis, which is mostly oriented OFF during inflammation but switches to the ON orientation when inflammation is resolved. We further detected increased abundances ofBacteroides fragilisassociated bacteriophages in patients with the PSA OFF orientation. Isolation and analysis of aBacteroides fragilisassociated bacteriophage revealed that it induced the PSA OFF switch, thereby altering the bacterial induced immune modulation. Altogether, we reveal large-scale dynamic and reversible bacterial phase variations driven both by bacteriophages and the host inflammatory state signifying bacterial functional plasticity and suggesting potential clinical interventions.

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When we think about bacteria, we often think first about disease. While there are many bacteria that cause diseases, there are also many other bacteria that are useful for human health. The human body has an enormous number of these good bacteria, which work together and with the immune system to protect us against diseases. In this article, we will discuss this relationship between the good bacteria living inside us and the immune system. We will explain how we can study these helpful bacteria, and describe the tools and methods at our disposal, such as special mice whose bodies do not contain any bacteria. Finally, we will describe how we can use the good bacteria living in the human body to advance medicine and drug development.