Nathaniel Ritz

Sulfate-reducing bacteria impairs working memory in mice.

The ability of gut microbes to bi-directionally communicate with the brain and vice versa form the basis of the gut microbiome-central nervous system axis. It has been shown that inoculation with pathogenic gut bacteria alters the behavior of mice; however, it is not known whether or not non-pathogenic resident microbes have similar effects. In this study, we tested the hypothesis that the administration of sulfate-reducing bacteria (SRB), a specific group of resident gut bacteria that generate hydrogen sulfide (H2S), impair learning and memory performance in mice tested in an 8-arm radial maze and Morris water maze. We found that mice spent more time in the center of the maze when they were gavaged with live SRB as compared to mice given saline (control), lactulose+mannitol (L/M), or killed SRB. SRB-gavaged mice were also tested using the Morris water maze and were found to take longer to complete the test, spend more time further from the platform, and have a longer path length to reach the platform. This effect of SRB on maze performance was associated with a higher concentration of H2S in the small intestine and cecum. We conclude that SRB, a specific resident gut bacterial species, could impair cognitive function in mice.

Sulfate‐reducing bacteria slow intestinal transit in a bismuth‐reversible fashion in mice

Hydrogen sulfide (H2S) serves as a mammalian cell‐derived gaseous neurotransmitter. The intestines are exposed to a second source of this gas by sulfate‐reducing bacteria (SRB). Bismuth subsalicylate binds H2S rendering it insoluble. The aim of this study was to test the hypothesis that SRB may slow intestinal transit in a bismuth‐reversible fashion.

Sulfur Cycling and the Intestinal Microbiome

In this review, we focus on the activities transpiring in the anaerobic segment of the sulfur cycle occurring in the gut environment where hydrogen sulfide is produced. While sulfate-reducing bacteria are considered as the principal agents for hydrogen sulfide production, the enzymatic desulfhydration of cysteine by heterotrophic bacteria also contributes to production of hydrogen sulfide. For sulfate-reducing bacteria respiration, molecular hydrogen and lactate are suitable as electron donors while sulfate functions as the terminal electron acceptor. Dietary components provide fiber and macromolecules that are degraded by bacterial enzymes to monomers, and these are fermented by intestinal bacteria with the production to molecular hydrogen which promotes the metabolic dominance by sulfate-reducing bacteria. Sulfate is also required by the sulfate-reducing bacteria, and this can be supplied by sulfate- and sulfonate-containing compounds that are hydrolyzed by intestinal bacterial with the release of sulfate. While hydrogen sulfide in the intestinal biosystem may be beneficial to bacteria by increasing resistance to antibiotics, and protecting them from reactive oxygen species, hydrogen sulfide at elevated concentrations may become toxic to the host.

Tu1871 Excretion of Breath Hydrogen Is Reduced by Inhibition of Sulfate Reduction by Molybdate in Rats

G A A b st ra ct s increased in the DRG during colitis contains CREB binding sequence in its promoter thus is responsive to CREB activity. AIMS: 1) To examine the phosphorylation of CREB and expression of CGRP by BDNF in vivo and in vitro; and 2) To examine whether the PLC/ calcium pathway is involved in BDNF-induced CREB phosphorylation.METHODS: Colonic inflammation was induced in rats by intracolonic instillation of trinitrobenzene sulfonic acid (TNBS: 1.5 mL/kg of 60 mg/mL solution in 50% EtOH). Control animals received 50% EtOH. Rats were killed on day 3 or 7 following the induction of colitis. CREB phosphorylation was examined by western blot and immunohistochemistry with a specific antibody recognizing CREB phospho-serine 133. The pair-matched DRG explants culture were incubated with BDNF (10 ng/mL) for various time points to examine the effects of BDNF signaling on CREB phosphorylation. Endogenous BDNF was blocked by BDNF neutralizing antibody (36 μg/ kg, i.v.). CGRP expression was examined by real-time PCR. RESULTS: Colitis increased CREB phosphorylation level in the L1 DRG at 3 days and 7 days post TNBS treatment examined by both western blot and immunohistochemistry. CREB phosphorylation in the DRG was expressed in small-to-medium sized sensory neurons. Anti-BDNF treatment of the colitic animals reduced colitis-induced CREB phosphorylation in the L1 DRG. Incubation of DRG explants with BDNF also increased CREB phosphorylation level which was blocked by inhibition of the phospholipase C (PLC) pathway with U-73122. Blockade of endogenous BDNF with BDNF neutralizing antibody also reversed colitis-induced up-regulation of CGRP transcripts in the L1 DRG. CONCLUSION: BDNF regulates CREB activity and CGRP expression through the PLC/calcium pathway in the DRG during colitis. The BDNF-PLC/ calcium-CREB-CGRP axis is an important component in visceral hypersensitivity during colitis.