Uses of Fecal Microbiota Transplantation in Neurodegenerative Disease: A Scoping Review.

Fecal microbiota transplantation (FMT) is the administration of fecal bacteria from a healthy donor into the intestinal tract of a recipient in order to directly change the recipient's gut microbial composition and confer a health benefit. The relationship between the gut microbiome and the central nervous system, termed the gut-brain axis, has been a frequent topic of gut microbiome studies. Commensal gut bacteria communicate with the central nervous system through various hormones, cytokines, and neural pathways. Therefore, influencing the gut microbiome via FMT may have the potential in treating symptoms of neurodegenerative conditions. This study aims to identify current uses of FMT in treating neurodegenerative diseases and highlight areas of future investigation. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework, a literature search was conducted of peer-reviewed sources on September 27, 2022, from Embase, MEDLINE, Web of Science, and Cochrane Central. Search terms were utilized that were related to the application of FMT and neurodegenerative disorders and limited those human studies, those that were published in English, and those that were published between 2017 and 2022. The initial search yielded 450 unique articles, and after the assessment of the title and abstract for inclusion and exclusion criteria, six articles were identified for full-text review. Studies that focused on either Parkinson's disease (PD) or multiple sclerosis (MS) demonstrated improvements in both motor symptoms and non-motor symptoms. FMT was also shown to provide significant relief of constipation and general gastrointestinal (GI) symptoms in all conditions studied. The studies related to MS showed the most mixed results with regard to symptomatic improvement. The data on the use of FMT as a treatment for neurodegenerative disorders is limited; however, studies have shown not only improvement in GI symptoms but also improvement in the cognitive symptoms of PD and dementia. The data on FMT as a treatment to improve the motor symptoms of PD is both more complete and more compelling than the data on the motor symptoms of MS. The studies that were reviewed showed no major adverse effects of FMT and generally promising results. There is a strong case to be made for larger, more well-controlled studies to be done on FMT and its potential use as a treatment not only for GI symptoms but for the motor and cognitive symptoms of neurodegenerative diseases.

High-fructose corn syrup-sweetened soft drink consumption increases vascular resistance in the kidneys at rest and during sympathetic activation.

We first tested the hypothesis that consuming a high-fructose corn syrup (HFCS)-sweetened soft drink augments kidney vasoconstriction to sympathetic stimulation compared with water (study 1). In a second study, we examined the mechanisms underlying these observations (study 2). In study 1, 13 healthy adults completed a cold pressor test, a sympathoexcitatory maneuver, before (preconsumption) and 30 min after drinking 500 mL of decarbonated HFCS-sweetened soft drink or water (postconsumption). In study 2, venous blood samples were obtained in 12 healthy adults before and 30 min after consumption of 500 mL water or soft drinks matched for caffeine content and taste, which were either artificially sweetened (Diet trial), sucrose-sweetened (Sucrose trial), or sweetened with HFCS (HFCS trial). In both study 1 and study 2, vascular resistance was calculated as mean arterial pressure divided by blood velocity, which was measured via Doppler ultrasound in renal and segmental arteries. In study 1, HFCS consumption increased vascular resistance in the segmental artery at rest (by 0.5 ± 0.6 mmHg·cm-1·s-1, P = 0.01) and during the cold pressor test (average change: 0.5 ± 1.0 mmHg·cm-1·s-1, main effect: P = 0.05). In study 2, segmental artery vascular resistance increased in the HFCS trial (by 0.8 ± 0.7 mmHg·cm-1·s-1, P = 0.02) but not in the other trials. Increases in serum uric acid were greater in the HFCS trial (0.3 ± 0.4 mg/dL, P ≤ 0.04) compared with the Water and Diet trials, and serum copeptin increased in the HFCS trial (by 0.8 ± 1.0 pmol/L, P = 0.06). These findings indicate that HFCS acutely increases vascular resistance in the kidneys, independent of caffeine content and beverage osmolality, which likely occurs via simultaneous elevations in circulating uric acid and vasopressin.

An Isoform-Selective PTP1B Inhibitor Derived from Nitrogen-Atom Augmentation of Radicicol.

A library of natural products and their derivatives was screened for inhibition of protein tyrosine phosphatase (PTP) 1B, which is a validated drug target for the treatment of obesity and type II diabetes. Of those active in the preliminary assay, the most promising was compound 2 containing a novel pyrrolopyrazoloisoquinolone scaffold derived by treating radicicol (1) with hydrazine. This nitrogen-atom augmented radicicol derivative was found to be PTP1B selective relative to other highly homologous nonreceptor PTPs. Biochemical evaluation, molecular docking, and mutagenesis revealed 2 to be an allosteric inhibitor of PTP1B with a submicromolar Ki. Cellular analyses using C2C12 myoblasts indicated that 2 restored insulin signaling and increased glucose uptake.