Marginal Zinc Deficiency Aggravated Intestinal Barrier Dysfunction and Inflammation through ETEC Virulence Factors in a Mouse Model of Diarrhea

Wang, Peng; Chen, Qianqian; Gan, Liping; Du, Xinyu; Li, Qiyue; Qiao, Hanzhen; Zhao, Yuqing; Huang, Jin; Wang, JinRong

doi:10.3390/vetsci9090507

Cited by 2 publications

(3 citation statements)

References 38 publications

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“…At the same time, the pathogenicity of ETEC is based on the secretion of LT and ST in the intestinal epithelium, which are the main causes of diarrhea symptoms [ 3 ]. Previous studies have demonstrated that dZn can obviously upregulate the mRNA expression of virulence genes in the cecum contents of ETEC infection mice [ 14 ]. In the present study, the increased expression of genes involved in cellular adhesion (FaeG), LT (eltA and eltB), ST (estB), and biofilm formation (bssS) in the cecum of mice induced by ETEC infection was prevented by pretreatment with ZnLa.…”

Section: Discussionmentioning

confidence: 99%

“…The ETEC infection was performed in accordance with our previous study [ 14 ]. Briefly, mice were treated with streptomycin (5 g/L) and fructose (67 g/L) in drinking water 36 h before the ETEC infection.…”

Section: Methodsmentioning

confidence: 99%

“…Zinc also plays a vital role in the growth, immunity, and mucous membranes through participation in the synthesis of nucleic acids and proteins, energy metabolism, and synthesizing a variety of important metabolic enzymes [ 13 ]. Our previous study demonstrated that zinc alleviated diarrhea induced by ETEC in a virulence-factors-dependent manner [ 14 ]. However, the low availability of zinc in an inorganic form limits its use in practice; this prompted us to develop organic forms of zinc with a higher bacterial inhibitory capacity.…”

Section: Introductionmentioning

confidence: 99%

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Zinc Laurate Protects against Intestinal Barrier Dysfunction and Inflammation Induced by ETEC in a Mice Model

Chen

Wang

et al. 2022

Nutrients

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Enterotoxigenic Escherichia coli (ETEC) infection is one of the most common bacterial causes of diarrhea in children and young farm animals. Medium-chain fatty acids (MCFAs) have been widely used for their antibacterial and immune functions. However, there is limited information regarding the role of MCFAs chelated with Zn in diarrhea induced by ETEC infection. Here, zinc laurate (ZnLa) was used to evaluate its protective effect in a mice diarrhea model induced by ETEC. A total of 45 ICR-weaned female mice were randomly assigned to marginal zinc deficiency (dZn), dZn, and ETEC infection groups (dZn+ETEC); ETEC infection was co-treated with a low, middle, or high dose of ZnLa (ZnLa LOW+ETEC, ZnLa MID+ETEC, and ZnLa HIGH+ETEC), respectively, to explore the effect and its mechanism of ZnLa on diarrhea and intestinal health of mice challenged with ETEC. To further compare the antibacterial efficiency of ZnLa and ZnSO4 in mice with ETEC infection, a total of 36 ICR-weaned female mice were randomly divided into ZnLa, ZnLa+ETEC, ZnSO4, and ZnSO4 and ETEC infection groups (ZnSO4+ETEC); moreover, the growth curve of ETEC also compared ZnLa and ZnSO4 in vitro. Mice pretreated with ZnLa were effectively guarded against body weight losses and increases in diarrhea scores induced by ETEC. ZnLa pretreatment also prevented intestinal barrier damage and ion transport in mice challenged with ETEC, as evidenced by the fact that the intestinal villus height and the ratio of villus height and crypt depth, tight junction protein, and Na+ absorption were higher, whereas intestinal permeability and anion secretion were lower in mice pretreated with ZnLa. In addition, ZnLa conferred effective protection against ETEC-induced intestinal inflammatory responses, as the increases in protein and mRNAs of proinflammatory cytokines were prevented in serum and jejunum, which was likely associated with the TLR4/MYD88/NF-κB signaling pathway. The increase in ETEC shedding and virulence-related gene expression was prevented in mice with ZnLa pretreatment. Finally, the growth of ETEC and virulence-related gene expression were lower in the ZnLa group than in ZnSO4 with an equal concentration of zinc. These findings suggest that ZnLa is a promising prevention strategy to remedy ETEC infection.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Zinc Laurate Protects against Intestinal Barrier Dysfunction and Inflammation Induced by ETEC in a Mice Model

Chen

Wang

et al. 2022

Nutrients

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Zinc status and indicators of intestinal health in enterotoxigenic Escherichia coli F18 challenged newly weaned pigs fed diets with different levels of zinc

Hansen,

Canibe,

Nielsen

et al. 2024

Journal of Animal Science

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This study investigated the impact of an enterotoxigenic Escherichia coli (ETEC) F18 challenge on newly weaned pigs when fed one of three Zn levels (150, 1,400, or 2,500 ppm) on performance, Zn status, ETEC shedding, and diarrhea. The ETEC challenge was hypothesized to have a more pronounced negative impact on pigs fed a diet containing 150 ppm Zn compared to 1,400 or 2,500 ppm Zn for 14 d after weaning. The study included 72 ETEC F18 susceptible pigs weaned at approximately 28 d of age (d 0 of the study). The pigs were distributed according to initial weight and litter to one of the three dietary Zn levels. Half of the pigs were challenged with ETEC on d 1 and 2. The challenge reduced (P ≤ 0.03) feed intake and average daily gain (ADG) during d 3-5. Challenged pigs fed 150 ppm Zn had lower (P = 0.01) ADG during d 5-7 compared to those fed 1,400 or 2,500 ppm Zn, whereas control pigs’ ADG were not affected by dietary Zn content. Challenged pigs fed 150 ppm Zn also showed lower (P < 0.01) fecal dry matter (DM) on d 5 compared to control pigs fed 150 ppm Zn and challenged pigs fed 1,400 or 2,500 ppm Zn. Challenge increased (P < 0.01) ETEC shedding in all groups, but challenged pigs fed 150 ppm Zn showed higher (P ≤ 0.05) fecal shedding of ETEC and toxins than when fed 1,400 or 2,500 ppm. On d 3, C-reactive protein concentration in plasma was lower (P < 0.03) for pigs fed 1,400 and 2,500 compared to 150 ppm Zn. Plasma haptoglobin and pig major acute phase protein were unaffected by dietary Zn content. On d 0, the serum Zn concentration was 586 ± 36.6 µg/L, which pigs fed 150 ppm Zn maintained throughout the study. The serum Zn concentration increased (P ≤ 0.07) in pigs fed 1,400 or 2,500 ppm Zn. The challenge decreased (P < 0.01) the serum Zn concentration in pigs fed 2,500 ppm Zn. On d 5 and 7, serum Zn concentration was similar for challenged pigs fed 1,400 and 2,500 ppm Zn, while control pigs fed 2,500 ppm Zn had higher (P < 0.01) serum Zn concentration than 1,400 ppm Zn. On d 7, serum Zn concentration tended (P = 0.08) to be lower for pigs with diarrhea (fecal DM ≤ 18%). In summary, these results indicate that newly weaned pigs fed 150 ppm Zn are more susceptible to ETEC F18 colonization and its adverse consequences such as diarrhea and reduced growth, even though challenge did not increase acute phase proteins.

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Marginal Zinc Deficiency Aggravated Intestinal Barrier Dysfunction and Inflammation through ETEC Virulence Factors in a Mouse Model of Diarrhea

Cited by 2 publications

References 38 publications

Zinc Laurate Protects against Intestinal Barrier Dysfunction and Inflammation Induced by ETEC in a Mice Model

Zinc Laurate Protects against Intestinal Barrier Dysfunction and Inflammation Induced by ETEC in a Mice Model

Zinc status and indicators of intestinal health in enterotoxigenic Escherichia coli F18 challenged newly weaned pigs fed diets with different levels of zinc

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