Written by Angeline A. De Leon, Staff Writer. This study demonstrates that L. brevis 23017 effectively prevents Hg-induced injury by promoting Hg binding in the small intestine, by preserving the integrity of the intestinal barrier, reducing intestinal epithelial cell cytotoxicity, protecting TJ proteins, and modulating inflammation and alleviating oxidative stress through both MAPK and NF-κB pathways.
Exposure to mercury (Hg), one of the most toxic elements in the environment, has tremendous harmful effects on human health. Natural sources of mercury include fish and plants 1, but the heavy metal is also heavily used in the painting, mining, and hydroelectric industries 2. Mercury exposure is associated with everything from cardiovascular dysfunction and cancer to renal failure and reproductive disease 3. Newer research is also showing that mercury exposure can adversely affect the gut microbiome 4, damaging tight junction proteins (network of proteins maintaining intestinal barrier and regulating its permeability) and causing inflammation to epithelial cells lining the intestines 5. Certain Lactobacillus strains, including Lactobacillus plantarum and Bacillus coagulans 6, appear to protect against heavy metal toxicity. Studies suggest that Lactobacillus may mitigate inflammation by inhibiting p38 mitogen-activated protein kinases (p 38 MAPK) and nuclear-factor-kB (NF-kB) pathways (both implicated in the production of inflammatory mediators) 7. In a follow-up study 8 published in Frontiers in Microbiology (2018), researchers examined whether this same probiotic strain could protect the gut barrier against toxic mercury exposure in mice, looking specifically at its effects on the p38 MAPK and NF-kB pathways.
L. brevis 23017 was suspended in Lactobacillus MRS agar medium, and a litter of 50 of 4-week-old female mice was evenly divided into five groups: (1) a control group orally dosed with 200 µ L MRS medium; (2) a group dosed with 200 µ L MRS medium for the first 5 days and then an oral solution of Hg (10 mg/kg) on the sixth day (Hg-5d); (3) a group dosed with L. brevis 23017 (109 CFU/200 µ L) for the first 5 days and then an oral solution of Hg (10 mg/kg) on the sixth day (LAB + Hg-5d); (4) a group dosed with 200 µ L MRS medium for the first 5 days, an oral solution of Hg (10 mg/kg) on the sixth day, and then MRS medium again for the last 6 days (Hg-12d); and (5) a group dosed with L. brevis 23017 (109 CFU/200 µ L) for the first 5 days, an oral solution of Hg (10 mg/kg) on the sixth day, and then L. brevis again for the last 6 days (LAB + Hg-12d). Mercury content in feces and muscle was determined using an absorption spectrometry technique, and intestinal tissues were collected from areas of the pancreas and colon for histological examination and analysis of antioxidant activity. Total RNA was extracted from intestinal tissues using an RNA extraction kit, and levels of cytokine gene products (cytokine gene expression) were determined. Finally, Western blot analysis was used to analyze intestinal segments for protein concentrations (p38 MAPK and NF-kB).
Histopathological examinations revealed that while mice exposed to mercury (Hg-5d and Hg-12d) presented with ruptured small intestinal cells, the lactobacillus groups (LAB + Hg-5d and LAB + Hg-12d) retained integrity of the small intestinal villus (involved in nutrient absorption), with the LAB + Hg-12d group showing longer intestinal villus than the LAB + Hg-5d group. Researchers also found that both LAB groups showed significantly lower levels of Hg in muscle tissue, relative to their respective exposure groups (p < 0.05 for both). Analysis of antioxidant activity in Hg-exposed intestinal tissues showed that LAB significantly increased superoxide dismutase (SOD) and glutathione (GSH) (antioxidant) levels and decreased catalase (CAT) and (malondialdehyde) MDA (markers of oxidative stress) levels in the duodenum and colon (p < 0.05 for all). Both LAB groups exhibited higher expression levels of IL-10 (an anti-inflammatory cytokine) in the duodenum and colon, relative to controls (p < 0.05 for both), and increased expression of ZO-1 (tight junction protein) in the duodenum, relative to respective exposed groups (p < 0.01 for both). Finally, Western blot analysis revealed that for the LAB groups, P38 (p < 0.01 for LAB + Hg-5d and p < 0.05 LAB + Hg-12d) and p-NF-kB (p < 0.05 for LAB + Hg-5d and p < 0.01 for LAB + Hg-12d) proteins in the duodenum were inactivated, compared to respective Hg-exposed groups. Both groups of LAB-treated mice also showed reduced expression of P38 in the colon, relative to exposed groups (p < 0.01 for both).
Altogether, evidence from the present study indicates that the Lactobacillus strain L. brevis 23017 is capable of protecting gut barrier function against mercury toxicity in mice. Through various methodologies, researchers demonstrated that L. brevis 23017 can mitigate heavy metal toxicity by preserving integrity of intestinal villi architecture, inhibiting absorption of mercury in the muscle, maintaining relative integrity of tight junction proteins, and reducing inflammation and oxidative stress in the duodenum and colon through the p38 MAPK and NF-kB pathways. Findings elucidate the mechanisms associated with the Lactobacillus strain’s protective action at the gut barrier, confirming its powerful role in mitigating heavy metal toxicity and its overall value as a functional fermented food. Prospective studies are needed to examine the efficacy of L. brevis 23017 in a human model of mercury exposure.
Source: Jiang X, Gu S, Lu D, et al. Lactobacillus brevis 23017 relieves mercury toxicity in the colon by modulation of oxidative stress and inflammation through the interplay of MAPK and NF-kB signaling cascades. Frontiers in Microbiology. 2018; 9: 245. DOI: 10.3389/fmicb.2018.0245.
Copyright © 2018 Jiang, Gu, Liu, Zhao, Xia, He, Chen and Ge. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CCBY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Frontiers
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Posted March 18, 2019.
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