reuteri 6475 are closely linked with the bacterium’s ability to produce histamine. In vitro studies using a human monocytoid cell line demonstrate that the anti-inflammatory effects of L. This strain has also been shown to reduce production of proinflammatory cytokines by primary macrophages isolated from pediatric Crohn’s Disease patients and to diminish antibiotic-associated side effects in Helicobacter pylori infected patients. reuteri ATCC PTA 6475 (also known as strain MM4-1A) has been shown to reduce inflammation in murine models of colitis and inflammation-associated colorectal cancer. In particular, the human breast milk-derived strain L. Strains from multiple human-associated clades have been used successfully as probiotics. Members of this species can have varied probiotic effects determined by their strain-level genetic diversity. The model probiotic organism, Lactobacillus reuteri is a gram-positive LAB that can be found as a commensal organism among many hosts, including birds, pigs, rodents and humans. It may be difficult to ensure the optimal intracellular conditions for production of either natural or exogenous products in a heterogeneous environment such as the mammalian gastrointestinal tract. While some bacteria maintain their intracellular pH and the ion gradients across their membranes within narrow boundaries, the lactic acid bacteria (LAB) can tolerate large shifts in these values in response to their extracellular environment.
However, bacterial enzyme activity is often affected by pH, and many metabolite transporters rely on voltage- or ion transport-dependent gating mechanisms. reuteri and other gut microbes.īacterial enzymes enable the production of microbial metabolites by the microbiome and confer important effects on microbiome:host dynamics. ClC transporters may serve as tunable modulators for histamine production by L. Histamine production is a potentially beneficial feature for intestinal microbes by promoting long-term colonization and suppression of inflammation and host immune responses.
ClC transport also alters the expression and activity of two key HDC genes: the histidine decarboxylase ( hdcA) and the histidine/histamine exchanger ( hdcP). Using fluorescent reporter assays, we further show that ClC transporters affect histamine output by altering intracellular pH and membrane potential. When the transport activity of either proton/chloride antiporter is disrupted by genetic manipulation, bacterial histamine output is reduced. reuteri possesses two ClC transporters, EriC and EriC2, as well as a complete histidine decarboxylase gene cluster (HDC) for the synthesis and export of histamine. Here we examine the histidine decarboxylase system in relation to ClC antiporters in the probiotic organism Lactobacillus reuteri. This family is unique among transporters by facilitating ion flux in either direction. Chloride channel (ClC)-family proton/chloride antiporters have been proposed to act as electrochemical shunts in conjunction with amino acid decarboxylase systems, correcting ion imbalances generated by decarboxylation through fixed ratio exchange of two chloride ions for one proton. reuteri, histamine synthesis and secretion requires l-histidine decarboxylase and a l-histidine/histamine exchanger. Histamine is a key mediator of the anti-inflammatory activity conferred by the probiotic organism Lactobacillus reuteri ATCC PTA 6475 in animal models of colitis and colorectal cancer.
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