salicylates and Constipation

Clinicians administering potent therapeutic agents must be aware of their side-effects. The gut is an important site of adverse drug reactions and drug-induced disease must always be considered in the differential diagnosis of patients presenting with gastrointestinal symptoms. A careful drug history must therefore be taken in all such patients. Symptoms can often be related to drug ingestion, but late effects also occur. The presence of blood in vomitus or stool is pathognomonic of serious pathology which may be drug-induced and requires further investigation. Upper gastrointestinal haemorrhage and pseudomembranous colitis are potentially fatal manifestations of drug therapy. Gastrointestinal symptoms can often be avoided if therapy is taken with meals or in a smaller dose, but drug withdrawal is always the first line of management in patients whose symptoms may be drug-induced.

Topics: Adrenal Cortex Hormones; Cathartics; Colon; Constipation; Diarrhea; Enterocolitis, Pseudomembranous; Esophagus; Gastrointestinal Diseases; Humans; Indomethacin; Intestine, Small; Mouth Mucosa; Phenylbutazone; Propionates; Prostaglandins; Salicylates; Staphylococcal Infections; Stomach; Stomatitis; Tongue

Gut microbiome alterations in Parkinson disease (PD) have been reported repeatedly, but their functional relevance remains unclear. Fecal metabolomics, which provide a functional readout of microbial activity, have scarcely been investigated. We investigated fecal microbiome and metabolome alterations in PD, and their clinical relevance.. Two hundred subjects (104 patients, 96 controls) underwent extensive clinical phenotyping. Stool samples were analyzed using 16S rRNA gene sequencing. Fecal metabolomics were performed using two platforms, nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-mass spectrometry.. Fecal microbiome and metabolome composition in PD was significantly different from controls, with the largest effect size seen in NMR-based metabolome. Microbiome and NMR-based metabolome compositional differences remained significant after comprehensive confounder analyses. Differentially abundant fecal metabolite features and predicted functional changes in PD versus controls included bioactive molecules with putative neuroprotective effects (eg, short chain fatty acids [SCFAs], ubiquinones, and salicylate) and other compounds increasingly implicated in neurodegeneration (eg, ceramides, sphingosine, and trimethylamine N-oxide). In the PD group, cognitive impairment, low body mass index (BMI), frailty, constipation, and low physical activity were associated with fecal metabolome compositional differences. Notably, low SCFAs in PD were significantly associated with poorer cognition and low BMI. Lower butyrate levels correlated with worse postural instability-gait disorder scores.. Gut microbial function is altered in PD, characterized by differentially abundant metabolic features that provide important biological insights into gut-brain pathophysiology. Their clinical relevance further supports a role for microbial metabolites as potential targets for the development of new biomarkers and therapies in PD. ANN NEUROL 2021;89:546-559.

Topics: Aged; Ceramides; Chromatography, Liquid; Cognitive Dysfunction; Constipation; Fatty Acids, Volatile; Feces; Female; Frailty; Gastrointestinal Microbiome; Humans; Male; Mass Spectrometry; Metabolomics; Methylamines; Middle Aged; Parkinson Disease; Proton Magnetic Resonance Spectroscopy; RNA, Ribosomal, 16S; Salicylates; Sedentary Behavior; Sphingosine; Thinness; Ubiquinone

Topics: Abdominal Pain; Adult; Bismuth; Constipation; Fecal Impaction; Humans; Male; Organometallic Compounds; Radiography; Salicylates