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NLRP6-associated host microbiota composition impacts in the intestinal barrier to systemic dissemination of Brucella abortus.

ABSTRACT: Brucella abortus is a Gram-negative bacterium responsible for a worldwide zoonotic infection-Brucellosis, which has been associated with high morbidity rate in humans and severe economic losses in infected livestock. The natural route of infection is through oral and nasal mucosa but the invasion process through host gut mucosa is yet to be understood. Studies have examined the role of NLRP6 (NOD-like receptor family pyrin domain-containing-6 protein) in gut homeostasis and defense against pathogens. Here, we investigated the impact of gut microbiota and NLRP6 in a murine model of Ba oral infection. Nlrp6-/- and wild-type (WT) mice were infected by oral gavage with Ba and tissues samples were collected at different time points. Our results suggest that Ba oral infection leads to significant alterations in gut microbiota. Moreover, Nlrp6-/- mice were more resistant to infection, with decreased CFU in the liver and reduction in gut permeability when compared to the control group. Fecal microbiota transplantation from WT and Nlrp6-/- into germ-free mice reflected the gut permeability phenotype from the donors. Additionally, depletion of gut microbiota by broad-spectrum-antibiotic treatment prevented Ba replication in WT while favoring bacterial growth in Nlrp6-/-. Finally, we observed higher eosinophils in the gut and leukocytes in the blood of infected Nlrp6-/- compared to WT-infected mice, which might be associated to the Nlrp6-/- resistance phenotype. Altogether, these results indicated that gut microbiota composition is the major factor involved in the initial stages of pathogen host replication and partially also by the resistance phenotype observed in Nlrp6 -/- mice regulating host inflammation against Ba infection.

SUBMITTER: Rungue M

PROVIDER: S-EPMC7932538 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Ferrous glycinate (Fe-Gly) has been increasingly used as iron fortification in the diets of weaned piglets and broilers, but the effect of Fe-Gly on intestinal barrier function in meat ducks has not been well defined. This study therefore investigated the effect of Fe-Gly on apparent nutrient utilization, hematological indices, intestinal morphological parameters, intestinal barrier function and microbial composition in meat ducks. A total of 672 one-day-old Cherry Valley ducks were randomly divided into 6 treatments (8 replicates for each treatment and 14 ducks for each replicate) and fed diets with 0 (control), 30, 60, 90 and 120 mg/kg Fe-Gly or 120 mg/kg FeSO4 for 35 d. The results showed that diets supplemented with Fe-Gly significantly increased average daily gain (ADG), average daily feed intake (ADFI), hematocrit (HCT), mean cell volume (MCV), the apparent utilization of dry matter (DM) and metabolizable energy (ME), villus height (VH) and villus height-to-crypt depth ratio (V:C) (P < 0.05). Fe-Gly also significantly up-regulated barrier-related genes including zonula occludens-1 (ZO-1), zonula occludens-2 (ZO-2), mucin 2 (MUC2) and lysozyme (LYZ) (P < 0.05), and down-regulated the mRNA expression of claudin-2 (CLDN2) and occludin (OCLN) in the jejunum (P < 0.05). The 16S rRNA sequence analysis indicated that the diet with Fe-Gly had a higher relative abundance of Intestinimonas and Romboutsia (P < 0.05), which have an ability to produce short chain fatty acids (SCFAs), especially butyric acid. It also decreased the relative abundance of pathobiont, including Megamonas, Eubacterium_coprostanoligenes_group and Plebeius (P < 0.05). Additionally, diets supplemented with 120 mg/kg Fe-Gly significantly increased the apparent utilization of DM and ME (P < 0.05) and decreased the relative abundance of Megamonas_unclassified and Bacteroides_unclassified compared with those fed 120 mg/kg FeSO4 (P < 0.05). These results revealed that diets supplemented with Fe-Gly exerted a potent beneficial effect on physical, chemical, immune and microbial barriers, thereby improving the integrity of the intestinal structure, promoting the digestion and absorption of nutrients to a certain extent, and ultimately elevating the growth performance of ducks.

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NLRP6-associated host microbiota composition impacts in the intestinal barrier to systemic dissemination of Brucella abortus.

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