Dataset Information

Gut Symptoms, Gut Dysbiosis and Gut-Derived Toxins in ALS.

ABSTRACT: Many pathogenetic mechanisms have been proposed for amyotrophic lateral sclerosis (ALS). Recently, there have been emerging suggestions of a possible role for the gut microbiota. Gut microbiota have a range of functions and could influence ALS by several mechanisms. Here, we review the possible role of gut-derived neurotoxins/excitotoxins. We review the evidence of gut symptoms and gut dysbiosis in ALS. We then examine a possible role for gut-derived toxins by reviewing the evidence that these molecules are toxic to the central nervous system, evidence of their association with ALS, the existence of biochemical pathways by which these molecules could be produced by the gut microbiota and existence of mechanisms of transport from the gut to the blood and brain. We then present evidence that there are increased levels of these toxins in the blood of some ALS patients. We review the effects of therapies that attempt to alter the gut microbiota or ameliorate the biochemical effects of gut toxins. It is possible that gut dysbiosis contributes to elevated levels of toxins and that these could potentially contribute to ALS pathogenesis, but more work is required.

SUBMITTER: Lee A

PROVIDER: S-EPMC10856138 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Gut Symptoms, Gut Dysbiosis and Gut-Derived Toxins in ALS.

Lee Aven A Henderson Robert R Aylward James J McCombe Pamela P

International journal of molecular sciences 20240203 3

Many pathogenetic mechanisms have been proposed for amyotrophic lateral sclerosis (ALS). Recently, there have been emerging suggestions of a possible role for the gut microbiota. Gut microbiota have a range of functions and could influence ALS by several mechanisms. Here, we review the possible role of gut-derived neurotoxins/excitotoxins. We review the evidence of gut symptoms and gut dysbiosis in ALS. We then examine a possible role for gut-derived toxins by reviewing the evidence that these m ...[more]

PMID: 38339149

Similar Datasets

Project description:BackgroundPrior studies on the role of gut-microbiome in Amyotrophic Lateral Sclerosis (ALS) pathogenesis have yielded conflicting results. We hypothesized that gut- and oral-microbiome may differentially impact two clinically-distinct ALS subtypes (spinal-onset ALS (sALS) vs. bulbar-onset ALS (bALS), driving disagreement in the field.MethodsALS patients diagnosed within 12 months and their spouses as healthy controls (n = 150 couples) were screened. For eligible sALS and bALS patients (n = 36) and healthy controls (n = 20), 16S rRNA next-generation sequencing was done in fecal and saliva samples after DNA extractions to examine gut- and oral-microbiome differences. Microbial translocation to blood was measured by blood lipopolysaccharide-binding protein (LBP) and 16S rDNA levels. ALS severity was assessed by Revised ALS Functional Rating Scale (ALSFRS-R).ResultssALS patients manifested significant gut-dysbiosis, primarily driven by increased fecal Firmicutes/Bacteroidetes-ratio (F/B-ratio). In contrast, bALS patients displayed significant oral-dysbiosis, primarily driven by decreased oral F/B-ratio. For sALS patients, gut-dysbiosis (a shift in fecal F/B-ratio), but not oral-dysbiosis, was strongly associated with greater microbial translocation to blood (r = 0.8006, P < 0.0001) and more severe symptoms (r = 0.9470, P < 0.0001). In contrast, for bALS patients, oral-dysbiosis (a shift in oral F/B-ratio), but not gut-dysbiosis, was strongly associated with greater microbial translocation to blood (r = 0.9860, P < 0.0001) and greater disease severity (r = 0.9842, P < 0.0001). For both ALS subtypes, greater microbial translocation was associated with more severe symptoms (sALS: r = 0.7924, P < 0.0001; bALS: r = 0.7496, P = 0.0067). Importantly, both sALS and bALS patients displayed comparable oral-motor deficits with associations between oral-dysbiosis and severity of oral-motor deficits in bALS but not sALS. This suggests that oral-dysbiosis is not simply caused by oral/bulbar/respiratory symptoms but represents a pathological driver of bALS.ConclusionsWe found increasing gut-dysbiosis with worsening symptoms in sALS patients and increasing oral-dysbiosis with worsening symptoms in bALS patients. Our findings support distinct microbial mechanisms underlying two ALS subtypes, which have been previously grouped together as a single disease. Our study suggests correcting gut-dysbiosis as a therapeutic strategy for sALS patients and correcting oral-dysbiosis as a therapeutic strategy for bALS patients.

Project description:BackgroundInfection with SARS-CoV-2, the virus responsible for COVID-19, can lead to a range of physical symptoms and mental health challenges, including stress, anxiety, and depression. These effects are particularly pronounced in hospitalized patients, likely due to the virus's direct and indirect impact on the nervous system. Gut dysbiosis, an imbalance in the gut microbiome, has been implicated in immune dysfunction and chronic inflammation in COVID-19 patients. However, the interactions between gut microbiome composition and the physical and mental symptoms of COVID-19 remain incompletely understood.MethodsWe investigated the association between physical and mental symptoms, cytokine profiles, and gut microbiota composition in 124 hospitalized COVID-19 patients. We collected data on demographics, COVID-19 severity, and mental health indicators (stress, anxiety, and depression). Gut microbiome profiling was performed using full-length 16 S rRNA gene sequencing to evaluate microbial diversity and composition.ResultsCOVID-19 severity was categorized as low (27.4%), moderate (29.8%), or critical (42.8%). Common symptoms included fever (66.1%) and cough (55.6%), while somatic symptoms (27.3%), anxiety (27.3%), depressive symptoms (39%), and stress (80.5%) were frequently self-reported. Elevated interleukin-6 levels in severe cases highlighted systemic inflammation, reduced gut bacterial diversity, particularly among women and obese patients, correlated with higher disease severity. Notably, the genus Mitsuokella was associated with increased physical symptoms and mental distress, while Granulicatella was linked to critical illness.ConclusionsOur findings reveal significant associations between mental health status, systemic inflammation, and gut dysbiosis in hospitalized COVID-19 patients. These results indicate the potential for microbiome-targeted therapies to mitigate psychological and physical complications and improve recovery outcomes in this population.

Dataset Information

Gut Symptoms, Gut Dysbiosis and Gut-Derived Toxins in ALS.

Publications

Gut Symptoms, Gut Dysbiosis and Gut-Derived Toxins in ALS.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets