Live lactic acid bacteria probiotics(Vsl Pharmaceuticals, Inc.)

Amyotrophic lateral sclerosis (ALS) is a neuromuscular disease. The ALS mice expressing human mutant of transactive response DNA binding protein of 43 kDa (hmTDP43) showed intestinal dysfunction before neuromuscular symptoms. We hypothesize that restoring the intestinal and microbial homeostasis with a bacterial metabolite or probiotics delays the ALS disease onset. We investigate the pathophysiological changes in the intestine and neurons, intestinal and blood-brain barriers, and inflammation during the ALS progression. We then cultured enteric glial cells (EGCs) isolated from TDP43 mice for mechanistic studies. TDP43 mice had significantly decreased intestinal mobility, increased permeability, and weakened muscle, compared with the age-matched wild-type mice. We observed increased hmTDP43 and Glial fibrillary acidic protein (GFAP), and decreased expression of α-smooth muscle actin (α-SMA), tight junction proteins (ZO-1 and Claudin-5) in the colon, spinal cord, and brain in TDP43 mice. TDP43 mice had reduced Butyryl-coenzyme A CoA transferase, decreased butyrate-producing bacteria Butyrivibrio fibrisolvens, and increased Bacteroides fragilis, compared to the WT mice. Serum inflammation cytokines (IL-6, IL-17, and IFN-γ) and LPS were elevated in TDP43 mice. EGCs from TDP43 mice showed aggregation of hmTDP43 associated with increased GFAP and ionized calcium-binding adaptor molecule (IBA1, a microglia marker). TDP43 mice treated with butyrate or probiotic VSL#3 had significantly increased rotarod time, increased intestinal mobility and decreased permeability, compared to the untreated group. Butyrate or probiotics treatment decreased the expression of GFAP, TDP43, and increased α-SMA, ZO-1, and Claudin-5 in the colon, spinal cord, and brain. Also, butyrate or probiotics treatment enhanced the Butyryl-coenzyme A CoA transferase, Butyrivibrio fibrisolvens, and reduced inflammatory cytokines in TDP43 mice. The TDP43 EGCs treated with butyrate or probiotics showed reduced GFAP, IBA1, and TDP43 aggregation. Restoring the intestinal and microbial homeostasis by beneficial bacteria and metabolites provide a potential therapeutic strategy to treat ALS.

Anxiety disorders represent one of the most common and debilitating illnesses worldwide. However, the development of novel therapeutics for anxiety disorders has lagged compared to other mental illnesses. A growing body of research suggests the gut microbiota plays a role in the etiopathology of anxiety disorders and may, therefore, serve as a novel target for their treatment through the use of probiotics. The use of dietary supplements like probiotics is increasing and their interaction with pharmacotherapies is not well understood. Utilizing the chick social-separation stress test, the primary aim of this study was to evaluate the commercially-available multi-strain probiotic found in VSL#3 for potential anxiolytic-like and/or antidepressant-like effects in the stress-vulnerable Black Australorp genetic line. A secondary aim was to evaluate the interaction between probiotics and the SSRI fluoxetine. Animals were treated with either saline, probiotics, fluoxetine, or probiotics + fluoxetine for 8 days prior to exposure to a 90-min isolation stressor that produces both a panic-like (i.e., anxiety-like) state followed by a state of behavioral despair (i.e., depression-like). The 8-day probiotic regimen produced anxiolytic-like effects but did not attenuate behavioral despair. Fluoxetine failed to significantly alter behavior in either of the two phases. Moreover, the combination of fluoxetine with probiotics attenuated the anxiolytic-like effects of probiotics. The fluoxetine + probiotics combination had no effect on behavioral despair. The results of the current study align with other preclinical studies and some clinical trials suggesting probiotics may offer beneficial effects on anxiety. Investigations examining the anxiolytic-like mechanism of probiotics are needed before any conclusions can be made. Additionally, as the use of probiotics becomes more popular, research on the interactions between probiotic-microbiota and psychotropic medications is necessary.