Sodium Humate-Derived Gut Microbiota Ameliorates Intestinal Dysfunction Induced by Typhimurium in Mice

Overview

Journal Microbiol Spectr

Specialty Microbiology

Date 2023 Apr 17

PMID 37067423

Authors

Dong Wang

Yingce Zheng

Yuying Fan

Yanjun He

Kexin Liu

Shouxiang Deng

Yun Liu

Affiliations

Soon will be listed here.

Abstract

is a foodborne pathogen that is one of the main causes of gastroenteric disease in humans and animals. As a natural organic substance, sodium humate (HNa) possesses antibacterial, antidiarrheal, and anti-inflammatory properties. However, it is unclear whether the HNa and HNa-derived microbiota exert alleviative effects on Salmonella enterica serovar Typhimurium-induced enteritis. We found that treatment with HNa disrupted the cell wall of . Typhimurium and decreased the virulence gene expression. Next, we explored the effect of HNa presupplementation on . Typhimurium-induced murine enteritis. The results revealed that HNa ameliorated intestinal pathological damage. In addition, we observed that presupplementation with HNa enhanced intestinal barrier function via modulating gut microbiota, downregulating toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) and NOD-like receptor protein 3 (NLRP3) signaling pathways, regulating intestinal mucosal immunity, and enhancing tight junction protein expression. To further validate the effect of HNa-derived microbiota on . Typhimurium-induced enteritis, we performed fecal microbiota transplantation and found that HNa-derived microbiota also alleviated . Typhimurium-induced intestinal damage. It is noteworthy that both HNa and HNa-derived microbiota improved the liver injury caused by . Typhimurium infection. Collectively, this is the first study to confirm that HNa could alleviate . Typhimurium-induced enteritis in a gut microbiota-dependent manner. This study provides a new perspective on HNa as a potential drug to prevent and treat salmonellosis. Typhimurium is an important zoonotic pathogen, widely distributed in nature. . Typhimurium is one of the leading causes of foodborne illnesses worldwide, and more than 350,000 people died from infection each year, which poses a substantial risk to public health and causes a considerable economic loss. Here, we found that the . Typhimurium infection caused severe intestinal and liver damage. In addition, we first found that sodium humate (HNa) and HNa-derived gut microbiota can alleviate . Typhimurium infection-induced intestinal damage. These findings extend the knowledge about the public health risk and pathogenic mechanisms of . Typhimurium.

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References

van Rensburg C . The Antiinflammatory Properties of Humic Substances: A Mini Review. Phytother Res. 2015; 29(6):791-5. DOI: 10.1002/ptr.5319. View

Li Y, Liu M, Zuo Z, Liu J, Yu X, Guan Y . TLR9 Regulates the NF-κB-NLRP3-IL-1β Pathway Negatively in -Induced NKG2D-Mediated Intestinal Inflammation. J Immunol. 2017; 199(2):761-773. DOI: 10.4049/jimmunol.1601416. View

Tapping R, Akashi S, Miyake K, Godowski P, Tobias P . Toll-like receptor 4, but not toll-like receptor 2, is a signaling receptor for Escherichia and Salmonella lipopolysaccharides. J Immunol. 2000; 165(10):5780-7. DOI: 10.4049/jimmunol.165.10.5780. View

Kovler M, Gonzalez Salazar A, Fulton W, Lu P, Yamaguchi Y, Zhou Q . Toll-like receptor 4-mediated enteric glia loss is critical for the development of necrotizing enterocolitis. Sci Transl Med. 2021; 13(612):eabg3459. PMC: 8859973. DOI: 10.1126/scitranslmed.abg3459. View

Dougan G, John V, Palmer S, Mastroeni P . Immunity to salmonellosis. Immunol Rev. 2011; 240(1):196-210. DOI: 10.1111/j.1600-065X.2010.00999.x. View

Furter M, Sellin M, Hansson G, Hardt W . Mucus Architecture and Near-Surface Swimming Affect Distinct Salmonella Typhimurium Infection Patterns along the Murine Intestinal Tract. Cell Rep. 2019; 27(9):2665-2678.e3. PMC: 6547020. DOI: 10.1016/j.celrep.2019.04.106. View

Na Y, Stakenborg M, Seok S, Matteoli G . Macrophages in intestinal inflammation and resolution: a potential therapeutic target in IBD. Nat Rev Gastroenterol Hepatol. 2019; 16(9):531-543. DOI: 10.1038/s41575-019-0172-4. View

Lu A, Magupalli V, Ruan J, Yin Q, Atianand M, Vos M . Unified polymerization mechanism for the assembly of ASC-dependent inflammasomes. Cell. 2014; 156(6):1193-1206. PMC: 4000066. DOI: 10.1016/j.cell.2014.02.008. View

Yuan Y, Liu Y, He Y, Zhang B, Zhao L, Tian S . Intestinal-targeted nanotubes-in-microgels composite carriers for capsaicin delivery and their effect for alleviation of Salmonella induced enteritis. Biomaterials. 2022; 287:121613. DOI: 10.1016/j.biomaterials.2022.121613. View

10.

Foley S, Tuohy C, Dunford M, Grey M, De Luca H, Cawley C . Gut microbiota regulation of P-glycoprotein in the intestinal epithelium in maintenance of homeostasis. Microbiome. 2021; 9(1):183. PMC: 8425172. DOI: 10.1186/s40168-021-01137-3. View

11.

Ji Y, Zhang A, Chen X, Che X, Zhou K, Wang Z . Sodium humate accelerates cutaneous wound healing by activating TGF-β/Smads signaling pathway in rats. Acta Pharm Sin B. 2016; 6(2):132-40. PMC: 4788707. DOI: 10.1016/j.apsb.2016.01.009. View

12.

Peterson L, Artis D . Intestinal epithelial cells: regulators of barrier function and immune homeostasis. Nat Rev Immunol. 2014; 14(3):141-53. DOI: 10.1038/nri3608. View

13.

Xu Z, Li D, Qu W, Yin Y, Qiao S, Zhu Y . Card9 protects sepsis by regulating Ripk2-mediated activation of NLRP3 inflammasome in macrophages. Cell Death Dis. 2022; 13(5):502. PMC: 9135688. DOI: 10.1038/s41419-022-04938-y. View

14.

Shi S, Wu S, Shen Y, Zhang S, Xiao Y, He X . Iron oxide nanozyme suppresses intracellular Enteritidis growth and alleviates infection . Theranostics. 2019; 8(22):6149-6162. PMC: 6299686. DOI: 10.7150/thno.29303. View

15.

Zegarra Ruiz D, Kim D, Norwood K, Saldana-Morales F, Kim M, Ng C . Microbiota manipulation to increase macrophage IL-10 improves colitis and limits colitis-associated colorectal cancer. Gut Microbes. 2022; 14(1):2119054. PMC: 9450902. DOI: 10.1080/19490976.2022.2119054. View

16.

Dey T, Bose P, Paul S, Karmakar B, Saha R, Gope A . Protective efficacy of fish oil nanoemulsion against non-typhoidal mediated mucosal inflammation and loss of barrier function. Food Funct. 2022; 13(19):10083-10095. DOI: 10.1039/d1fo04419b. View

17.

Pardo-Roa C, Salazar G, Noguera L, Salazar-Echegarai F, Vallejos O, Suazo I . Pathogenicity island excision during an infection by Salmonella enterica serovar Enteritidis is required for crossing the intestinal epithelial barrier in mice to cause systemic infection. PLoS Pathog. 2019; 15(12):e1008152. PMC: 6968874. DOI: 10.1371/journal.ppat.1008152. View

18.

Shi S, Qi Z, Sheng T, Tu J, Shao Y, Qi K . Antagonistic trait of Lactobacillus reuteri S5 against Salmonella enteritidis and assessment of its potential probiotic characteristics. Microb Pathog. 2019; 137:103773. DOI: 10.1016/j.micpath.2019.103773. View

19.

Wu J, Jiang R, Lin W, Ouyang G . Effect of salinity and humic acid on the aggregation and toxicity of polystyrene nanoplastics with different functional groups and charges. Environ Pollut. 2018; 245:836-843. DOI: 10.1016/j.envpol.2018.11.055. View

20.

Thompson A, Fulde M, Tedin K . The metabolic pathways utilized by Salmonella Typhimurium during infection of host cells. Environ Microbiol Rep. 2018; 10(2):140-154. DOI: 10.1111/1758-2229.12628. View