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. 2022 Jul 6:13:947655.
doi: 10.3389/fimmu.2022.947655. eCollection 2022.

Selenium Deficiency Leads to Inflammation, Autophagy, Endoplasmic Reticulum Stress, Apoptosis and Contraction Abnormalities via Affecting Intestinal Flora in Intestinal Smooth Muscle of Mice

Fuhan Wang  1 , Ni Sun  1 , Hanqin Zeng  1 , Yuan Gao  1 , Naisheng Zhang  1 , Wenlong Zhang  1
Affiliations

Selenium Deficiency Leads to Inflammation, Autophagy, Endoplasmic Reticulum Stress, Apoptosis and Contraction Abnormalities via Affecting Intestinal Flora in Intestinal Smooth Muscle of Mice

Fuhan Wang et al. Front Immunol. .

Abstract

Selenium (Se) is a micronutrient that plays a predominant role in various physiological processes in humans and animals. Long-term lack of Se will lead to many metabolic diseases. Studies have found that chronic Se deficiency can cause chronic diarrhea. The gut flora is closely related to the health of the body. Changes in environmental factors can cause changes in the intestinal flora. Our study found that Se deficiency can disrupt intestinal flora. Through 16s high-throughput sequencing analysis of small intestinal contents of mice, we found that compared with CSe group, the abundance of Lactobacillus, Bifidobacterium, and Ileibacterium in the low selenium group was significantly increased, while Romboutsia abundance was significantly decreased. Histological analysis showed that compared with CSe group, the small intestine tissues of the LSe group had obvious pathological changes. We examined mRNA expression levels in the small intestine associated with inflammation, autophagy, endoplasmic reticulum stress, apoptosis, tight junctions, and smooth muscle contraction. The mRNA levels of NF-κB, IκB, p38, IL-1β, TNF-α, Beclin, ATG7, ATG5, LC3α, BaK, Pum, Caspase-3, RIP1, RIPK3, PERK, IRE1, elF2α, GRP78, CHOP2, ZO-1, ZO-2, Occludin, E-cadherin, CaM, MLC, MLCK, Rho, and RhoA in the LSe group were significantly increased. The mRNA levels of IL-10, p62 BcL-2 and BcL-w were significantly decreased in the LSe group compared with the CSe group. These results suggest that changes in the abundance of Lactobacillus, bifidobacterium, ileum, and Romboutsia may be associated with cellular inflammation, autophagy, endoplasmic reticulum stress, apoptosis, tight junction, and abnormal smooth muscle contraction. Intestinal flora may play an important role in chronic diarrhea caused by selenium deficiency.

Keywords: ERS; apoptosis; autophagy; inflammatory; intestinal flora; selenium; smooth muscle contraction; tight junction.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Species accumulation box plot. The abscissa is the sample size; The y-coordinate is the number of OTU after sampling.
Figure 2
Figure 2
Histogram of relative abundance of species. (A) Histogram of relative abundance of sample species (Top 10, Genus). (B) Histogram of relative abundance of grouped species (Top 10, Genus). (C) Histogram of relative abundance of sample species (Top 35, Species). (D) Histogram of relative abundance of grouped species (Top 35, Species).
Figure 3
Figure 3
Phylogenetic tree analysis of genus level species.
Figure 4
Figure 4
Alpha Diversity index analysis. (A) Chao1 index; (B) Simpson index; (C) Shannon index; (D) Observed species index; (E) ACE index; (F) PD index (G) Good’s Coverage index.
Figure 5
Figure 5
Species dilution curve. (A) rarefaction Curve (Simple); (B) Rank Abundance (Simple);(C) rarefaction Curve (Group); (D) Rank Abundance (Group).
Figure 6
Figure 6
Analysis of differences in Beta diversity index between groups. (A) Beta-weighted-unifrac index; (B) Beta-unweighted-unifrac index; (C) PCA (Principal Component Analysis); (D) PCoA (principal coordinate analysis); (E) NMDS (non-metric multi-dimensional Scaling).
Figure 7
Figure 7
LefSe analysis of bacterial community structure in small intestinal contents of mice.
Figure 8
Figure 8
Tax4Fun function predictive analysis. According to the functional notes and abundance information of samples in the database, the top 35 functions and their abundance information in each sample were selected to draw a heat map. And cluster from the level of functional difference. The abscissa is the sample name and the ordinate is the feature comment.
Figure 9
Figure 9
Se deficiency caused apoptosis and injury of small intestine in mice. (A, B) Histopathology of small intestine. (A) CSe group; (a) An enlarged image of CSe Group; (B) LSe group; (b) An enlarged image of LSe group; (C, D) TUNEL analysis of small intestinal tissue; (C) CSe group; (D) LSe group.
Figure 10
Figure 10
Analysis of mRNA expression level in small intestine tissue. The Ct values measured by PCR were calculated by 2-△△ Ct and then standardized. The abscissa is the sample name and the ordinate is the gene name. p < 0.05.
See this image and copyright information in PMC

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