Excess glutamatergic neurotransmission may contribute to excitotoxic loss of nigrostriatal neurons in Parkinson’s disease (PD). Here, we determined if increasing glutamate uptake could reduce the extent of tyrosine hydroxylase (TH) loss in PD progression. The beta-lactam antibiotic, ceftriaxone, increases the expression of glutamate transporter 1 (GLT-1), a glutamate transporter that plays a major role in glutamate clearance in central nervous system and may attenuate adverse behavioral or neurobiological function in other neurodegenerative disease models. In association with >80 % TH loss, we observed a significant decrease in glutamate uptake in the established 6-hydroxydopamine (6-OHDA) PD model. Ceftriaxone (200 mg/kg, i.p.) increased striatal glutamate uptake with ≥ 5 consecutive days of injection in nonlesioned rats and lasted out to 14 days postinjection, a time beyond that required for 6-OHDA to produce >70 % TH loss (~9 days). When ceftriaxone was given at the time of 6-OHDA, TH loss was ~57 % compared to ~85 % in temporally matched vehicle-injected controls and amphetamine-induced rotation was reduced about 2-fold. This attenuation of TH loss was associated with increased glutamate uptake, increased GLT-1 expression, and reduced Serine 19 TH phosphorylation, a calcium-dependent target specific for nigrostriatal neurons. These results reveal that glutamate uptake can be targeted in a PD model, decrease the rate of TH loss in a calcium-dependent manner, and attenuate locomotor behavior associated with 6-OHDA lesion. Given that detection of reliable PD markers will eventually be employed in susceptible populations, our results give credence to the possibility that increasing glutamate uptake may prolong the time period before locomotor impairment occurs.

One carbon (1C) metabolism nutrients influence epigenetic regulation and they are supplied by diet and synthesized by gut microbiota. We examined the association between dietary consumption of methyl donors (methionine, betaine and choline) and B vitamins (folate, B2, B6, and B12) and the community composition and structure of the colonic mucosa-associated gut microbiota determined by 16S rRNA gene sequencing in 97 colonic biopsies of 35 men. We used the food frequency questionnaire to assess daily consumption of nutrients, and the UPARSE and SILVA databases for operational taxonomic unit classification. The difference in bacterial diversity and taxonomic relative abundance were compared between low versus high consumption of these nutrients. False discover rate (FDR) adjusted p value < 0.05 indicated statistical significance. The bacterial richness and composition differed significantly by the consumption of folate and B vitamins (p < 0.001). Compared with higher consumption, a lower consumption of these nutrients was associated with a lower abundance of Akkermansia (folate), Roseburia (vitamin B2), and Faecalibacterium (vitamins B2, B6, and B12) but a higher abundance of Erysipelatoclostridium (vitamin B2) (FDR p values < 0.05). The community composition and structure of the colonic bacteria differed significantly by dietary consumption of folate and B vitamins.

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INTRODUCTION: Studies have demonstrated health benefits of caffeine consumption, including decrease in cardiovascular disease, diabetes, and liver diseases. The exact mechanisms are not known. Caffeine consumption may possibly modulate the gut microbiome and therefore affect health and disease risk. We examined the association between caffeine consumption and the composition and structure of the colonic-gut microbiota. METHODS: In this study, 34 participants underwent a screening colonoscopy and had endoscopically normal colons. We obtained a total of 97 snap-frozen colonic mucosa biopsies from various segments of colon from these individuals. Microbial DNA was extracted, and subsequently amplified for the 16S rRNA gene V4 region and sequenced using the Illumina MiSeq platform. We analyzed the sequencing data using the UPARSE and SILVA database for operational taxonomic unit (OTU) classification. Self-administered BLOCK Food Frequency Questionnaire was used to ascertain daily caffeine consumption. We compared the diversity and relative abundance of bacterial taxonomies by high (≥82.9 mg) vs. low (<82.9 mg) consumption of caffeine. False discover rate (FDR) P-values were reported and <0.05 indicated statistical significance. RESULTS: The alpha diversity was the greatest in high caffeine consumers (Shannon index P < 0.0001). The beta diversity differed significantly between high vs. low caffeine drinkers (P = 0.0001). The composition of microbiomes did not differ at the phylum level based on caffeine consumption. At the genus level, high caffeine consumption was associated with increased relative abundance of Faecalibacterium (P < 0.0005) and Roseburia (P = 0.02), but decreased levels of Erysipelatoclostridium (P value <0.001) and an OTU belonging to the Lachnospiraceae family (Unc8895) (P < 0.0005). The observed association was seen regardless of age and dietary quality. Other bacteria commonly detected in gut microbiomes, including Odoribacter, Dialister, Fusicatenibactor, Alistipes, Blautia, and multiple members of Lachnospiraceae, were significantly more abundant (P < 0.05) in participants with higher caffeine consumption (Table 1). CONCLUSION: Higher caffeine consumption was associated with increased richness and evenness of the mucosa-associated gut microbiota, and higher relative abundance of anti-inflammatory bacteria, such as Faecalibacterium and Roseburia and lower levels of potentially harmful Erysipelatoclostridium.