Please cite this article as: S. Srivastav, S. Neupane, S. Bhurtel, et al., Probiotics mixture increases butyrate, and subsequently rescues the nigral dopaminergic neurons from MPTP and rotenone-induced neurotoxicity, The Journal of Nutritional Biochemistry, https://doi. AbstractMicrobiota in the gut affect brain physiology via various pathways, and dysbiosis seems to play a role in the pathogenesis of Parkinson's disease (PD). Probiotics showed pleiotropic effects on functions of the central nervous system via microbiota-gut-brain axis. However, no studies displayed the neuroprotective effects of probiotics in the Parkinson's disease. This study aimed to test the neuroprotective effects of probiotics in two different models of PD.We evaluated neuroprotective effects of a probiotic cocktail containing Lactobacillus rhamnosus GG, Bifidobacterium animalis lactis, and Lactobacillus acidophilus in PD models induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or rotenone utilizing behavioral tests, immunohistochemistry and neurochemical analysis. To assure the neuroprotection came from increased production of butyrate, we further determined beneficial effects of butyrate in the MPTP-mediated PD model. The probiotic mixture overtly protected the dopaminergic neurons against MPTP neurotoxicity. However, the probiotics downregulated expression of monoamine oxidase (MAO) B in the striatum, which was accompanied by a lower level of 1-methyl-4-phenylpyridinium (MPP + ), the main neurotoxic metabolite of MPTP. Thus, we extended the investigation into the rotenone-induced PD model. Rescuing effects of the probiotics were observed in the setup, which came with increased levels of neurotrophic factors and butyrate in the brain. Lactobacillus rhamnosus GG was identified to be a major contributor to the induction of neurotrophic factors and downregulation of MAO B. Finally, we demonstrated that sodium butyrate attenuated MPTPinduced neuronal loss in the nigrostriatal pathway. Probiotics could ameliorate neurodegeneration at least partially by increasing butyrate level. These data highlight the role of probiotics for brain health, and their potential as a preventive measure for neurodegenerative diseases such as PD. ACCEPTED MANUSCRIPT

The filamentous fungal pathogen Fusarium sp. causes several crop diseases. Some Fusarium sp. are endophytes that produce diverse valuable bioactive secondary metabolites. Here, extensive chemical investigation of the endophytic fungus, Fusarium sp. QF001, isolated from the inner rotten part of old roots of Scutellariae baicalensis resulted in the isolation of two new photosensitive geometrical isomers of lucilactaene (compounds 2 and 3) along with lucilactaene (6) and six other known compounds (fusarubin (1), (+)-solaniol (4), javanicin (5), 9-desmethylherbarine (7), NG391 (8) and NG393 (9)). Newly isolated isomers and lucilactaene were unstable under light at room temperature and tended to be a mixture in equilibrium state when exposed to a polar protic solvent during reversed phase chromatography. Normal phase chromatography under dim light conditions with an aprotic mobile phase led to the successful isolation of the relatively unstable isomers 2 and 3. Their structures were elucidated as 8(Z)-lucilactaene (2) and 4(Z)-lucilactaene (3) based on spectroscopic data. The absolute configuration of 4 was speculated to be R by computer-assisted specific rotation analysis. The isolated compounds could inhibit NO production and suppress pro-inflammatory cytokines expression in LPS-stimulated macrophage cells. These properties of the isolated compounds indicate their potential use as anti-inflammatory drugs.

Polyphasic taxonomic analysis was performed on a novel marine bacterium, designated as strain YJ057T, isolated from marine sediment collected in the Republic of Korea. The strain was Gram-negative, beige-colored, facultatively anaerobic, coccoid or ovoid-shaped and nonmotile. Preliminary 16S rRNA gene sequence-based phylogenetic analysis indicated that this novel marine isolate belongs to the family Rhodobacteraceae of the class Alphaproteobacteria, and has the greatest (96.2%) sequence similarity to Paracoccus aestuariivivens GHD-30T. Major (>10%) fatty acids of strain YJ057T were C16:0 and C18:1 ω7c, G+C content in the genomic DNA of the strain was 63.6 mol% and the sole respiratory quinone was ubiquinone Q-10. It had phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine and some unidentified components (three aminolipids, a glycolipid, a phospholipid and two lipids). As per the distinct phylogenetic position and combination of phenotypic and genotypic traits, the strain is considered a novel species of the genus Paracoccus, and the name Paracoccus ravus sp. nov. is proposed.