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Summary: Multiple sclerosis (MS) affects more than 2.8 million people worldwide but the distribution is not even. Although over 200 gene variants have been associated with susceptibility, studies of genetically identical monozygotic twin pairs suggest that the genetic make‐up is responsible for only about 20%–30% of the risk to develop disease, while the rest is contributed by milieu factors. Recently, a new, unexpected player has entered the ranks of MS‐triggering or facilitating elements: the human gut microbiota. In this review, we summarize the present knowledge of microbial effects on formation of a pathogenic autoreactive immune response targeting the distant central nervous system and delineate the approaches, both in people with MS and in MS animal models, which have led to this concept. Finally, we propose that a tight combination of investigations of human patients with studies of suitable animal models is the best strategy to functionally characterize disease‐associated microbiota and thereby contribute to deciphering pathogenesis of a complex human disease. [ABSTRACT FROM AUTHOR]

Objective: Autism spectrum disorders (ASD) are a varying group of disorders characterized by deficiency in social interaction and restrictive patterns of behavior and interests. While there are several studies focusing on the neuropsychiatric pathogenesis of ASD, its etiology remains unclear. The role of gut‐brain‐axis in ASD has been studied increasingly and a correlation between symptoms and the composition of gut microbiota has been documented in various works. Despite this, the significance of individual microbes and their function is still widely unknown. This work aims to elucidate the current knowledge of the interrelations between ASD and the gut microbiota in children based on scientific evidence. Methods: This is a systematic review done by a literature search focusing on the main findings concerning the gut microbiota composition, interventions targeting the gut microbiota, and possible mechanisms explaining the results in children aged between 2 and 18 years of age. Results: Most studies in this review found significant differences between microbial communities, while there was notable variation in results regarding diversity indices or taxonomic level abundance. The most consistent results regarding taxa differences in ASD children's gut microbiota were higher levels of Proteobacteria, Actinobacteria and Sutterella compared to controls. Conclusion: These results show that the gut microbiota of children with ASD is altered compared to one of neurotypically developed children. More research is needed to discover whether some of these features could be used as potential biomarkers for ASD and how the gut microbiota could be targeted in therapeutical interventions. [ABSTRACT FROM AUTHOR]

Background: Functional gastroduodenal disorders include functional dyspepsia, chronic nausea and vomiting syndromes, and gastroparesis. These disorders are common, but their overlapping symptomatology poses challenges to diagnosis, research, and therapy. This study aimed to introduce and validate a standardized patient symptom‐logging system and App to aid in the accurate reporting of gastroduodenal symptoms for clinical and research applications. Methods: The system was implemented in an iOS App including pictographic symptom illustrations, and two validation studies were conducted. To assess convergent and concurrent validity, a diverse cohort with chronic gastroduodenal symptoms undertook App‐based symptom logging for 4 h after a test meal. Individual and total post‐prandial symptom scores were averaged and correlated against two previously validated instruments: PAGI‐SYM (for convergent validity) and PAGI‐QOL (for concurrent validity). To assess face and content validity, semi‐structured qualitative interviews were conducted with patients. Key Results: App‐based symptom reporting demonstrated robust convergent validity with PAGI‐SYM measures of nausea (rS =0.68), early satiation (rS =0.55), bloating (rS =0.48), heartburn (rS =0.47), upper gut pain (rS =0.40), and excessive fullness (rS =0.40); all p < 0.001 (n = 79). The total App‐reported Gastric Symptom Burden Score correlated positively with PAGI‐SYM (rS =0.56; convergent validity; p < 0.001), and negatively with PAGI‐QOL (rS = −0.34; concurrent validity; p = 0.002). Interviews demonstrated that the pictograms had adequate face and content validity. Conclusions and Inferences: The continuous patient symptom‐logging App demonstrated robust convergent, concurrent, face, and content validity when used within a 4‐h post‐prandial test protocol. The App will enable standardized symptom reporting and is anticipated to provide utility in both research and clinical practice. [ABSTRACT FROM AUTHOR]

One‐third of epilepsy patients have drug‐resistant epilepsy (DRE), which is often complicated by polydrug toxicity and psychiatric and cognitive comorbidities. Advances in understanding the microbiome and gut‐brain‐axis are likely to shed light on epilepsy pathogenesis, anti‐seizure medication (ASM) resistance, and potential therapeutic targets. Gut dysbiosis is associated with inflammation, blood‐brain barrier disruption, and altered neuromodulators. High‐throughput and metagenomic sequencing has advanced the characterization of microbial species and functional pathways. DRE patients show altered gut microbiome composition compared to drug‐sensitive patients and healthy controls. The ketogenic and modified Atkins diets can reduce seizures in some patients with DRE. These low‐carbohydrate dietary therapies alter the taxonomic and functional composition of the gut microbiome, and composition varies between diet responders and nonresponders. Murine models suggest that specific phyla are necessary to confer efficacy from the diet, and antibiotic treatment may eliminate efficacy. The impact of diet might involve alterations in microbiota, promotion of select microbial interactions, and variance in brain neurotransmitter levels that then influence seizures. Understanding the mechanics of how diet manipulates seizures may suggest novel therapies. Most ASMs act on neuronal transmission via effects on ion channels and neurotransmitters. However, ASMs may also assert their effects via the gut microbiota. In animal models, the microbiota composition (eg, abundance of certain phyla) can vary with ASM active drug metabolites. Given the developing understanding of the gut microbiome in DRE, probiotics are another potential therapy. Probiotics alter the microbiota composition, and small studies suggest that these supplements can reduce seizures in some patients. DRE has enormous consequences to patients and society, and the gut microbiome holds promise as a potential therapeutic target. However, the exact mechanism and recognition of which patients are likely to be responders remain elusive. Further studies are warranted. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a chronic disorder characterized by inflammation of the gastrointestinal (GI) tract, and it is associated with different neurological disorders. Recent evidence has demonstrated that the gut‐brain‐axis has a central function in the perpetuation of IBS, and for this reason, it can be considered a possible therapeutic target. N‐Palmitoylethanolamine‐oxazoline (PEA‐OXA) possesses anti‐inflammatory and potent neuroprotective effects. Although recent studies have explained the neuroprotective properties of PEA‐OXA, nothing is known about its effects on the gut‐brain axis during colitis. The aim of this study is to explore the mechanism and the effect of PEA‐OXA on the gut‐brain axis in rats subjected to experimental colitis induced by oral administration of dextran sulfate sodium (DSS). Daily oral administration of PEA‐OXA (10 mg/kg daily o.s.) was able to decrease the body weight loss, macroscopic damage, colon length, histological alteration, and inflammation after DSS induction. Additionally, PEA‐OXA administration enhanced neurotrophic growth factor release and decreased the astroglial and microglial activation induced by DSS. Moreover, PEA‐OXA restored intestinal permeability and tight junctions (TJs) as well as reduced apoptosis in the colon and brain. In our work, we demonstrated, for the first time, the action of PEA‐OXA on the gut‐brain axis in a model of DSS‐induced colitis and its implication on the "secondary" effects associated with colonic disturbance. [ABSTRACT FROM AUTHOR]

In the course of Parkinson's disease (PD), the enteric nervous system (ENS) and parasympathetic nerves are amongst the structures earliest and most frequently affected by alpha-synuclein pathology. Accordingly, gastrointestinal dysfunction, in particular constipation, is an important non-motor symptom in PD and often precedes the onset of motor symptoms by years. Recent research has shown that intestinal microbiota interact with the autonomic and central nervous system via diverse pathways including the ENS and vagal nerve. The gut microbiome in PD has not been previously investigated. We compared the fecal microbiomes of 72 PD patients and 72 control subjects by pyrosequencing the V1-V3 regions of the bacterial 16S ribosomal RNA gene. Associations between clinical parameters and microbiota were analyzed using generalized linear models, taking into account potential confounders. On average, the abundance of Prevotellaceae in feces of PD patients was reduced by 77.6% as compared with controls. Relative abundance of Prevotellaceae of 6.5% or less had 86.1% sensitivity and 38.9% specificity for PD. A logistic regression classifier based on the abundance of four bacterial families and the severity of constipation identified PD patients with 66.7% sensitivity and 90.3% specificity. The relative abundance of Enterobacteriaceae was positively associated with the severity of postural instability and gait difficulty. These findings suggest that the intestinal microbiome is altered in PD and is related to motor phenotype. Further studies are warranted to elucidate the temporal and causal relationships between gut microbiota and PD and the suitability of the microbiome as a biomarker. © 2014 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]