Abstract
Objectives: To investigate the specific role of Toll-like receptor 4 (TLR4) in the regulation of the intestinal mucosa-associated microbiota by vitamin A (VA).Methods: Both TLR4-/- (knockout, KO) and wild-type (WT) female mice were randomly fed a VA normal (VAN) or VA deficient (VAD) diet for 4 weeks to establish the following four mouse model groups: TLR4-/- mice fed a VAN diet (KO VAN), TLR4-/- mice fed a VAD diet (KO VAD), WT mice fed a VAN diet (WT VAN), and WT mice fed a VAD diet (WT VAD). Then, the mice from each experimental group were mated with male mice with the same genetic background. The pups in the KO VAD and WT VAD groups were subsequently fed the VAD diet after weaning, while the pups in the KO VAN and WT VAN groups were fed the VAN diet continuously after weaning. The serum retinol levels of 7-week-old offspring were determined using high-performance liquid chromatography, and colons were collected from mice in each group and analyzed via 16S rRNA gene sequencing using an Illumina MiSeq platform to characterize the overall microbiota of the samples.Results: The abundance and evenness of the colon mucosa-associated microbiota were unaffected by dietary VA and TLR4 KO. VAD decreased the abundance of Anaerotruncus (Firmicutes), Oscillibacter (Firmicutes), Lachnospiraceae _NK4A136 _group (Firmicutes) and Mucispirillum (Deferribacteres) and increased the abundance of Parasutterella (Proteobacteria). TLR4 KO decreased the abundance of Bacteroides (Bacteroidetes) and Alloprevotella (Bacteroidetes). However, the abundance of Allobaculum (Firmicutes), Ruminiclostridium_9 (Firmicutes), Alistipes (Bacteroidetes), and Rikenellaceae_RC9 (Bacteroidetes) impacted the interaction between VA and TLR4.Conclusion: TLR4 may play a pivotal role in regulation of the intestinal mucosa-associated microbiota by VA to maintain the intestinal microecology.
Highlights
Vitamin A is an essential fat-soluble vitamin that maintains normal growth and development, participates in the immune response, promotes reproduction, and maintains visual function (Stephensen, 2001; Clagett-Dame and DeLuca, 2002)
To explore whether Toll-like receptor 4 (TLR4) participates in regulation of intestinal microbial homeostasis by vitamin A (VA), we established vitamin A normal (VAN) and vitamin A deficiency (VAD) mouse models in both TLR4−/− (KO VAN and KO VAD) and WT mice (WT VAN and with VAD (WT VAD))
Similar results were observed for the TLR4−/− mice, and the serum retinol levels were significantly repressed in the KO VAD group (0.328 ± 0.054 μmol/L) compared with those in the KO VAN group (1.171 ± 0.104 μmol/L)
Summary
Vitamin A is an essential fat-soluble vitamin that maintains normal growth and development, participates in the immune response, promotes reproduction, and maintains visual function (Stephensen, 2001; Clagett-Dame and DeLuca, 2002). Children experiencing VAD are especially prone to gastrointestinal (GI) tract infections (Thornton et al, 2014). Studies by us and others have shown that VAD can decrease gut integrity and impact the immune response of the GI tract in humans and animals (Quadro et al, 2000; Liu et al, 2014). The diversity and balance of the gut microbiota is important for maintaining the normal biological barrier function of the intestine (Topping and Clifton, 2001; Round et al, 2010). Our preliminary study found that VAD impacts the structural segregation of the gut microbiota in children with persistent diarrhea (Lv et al, 2016)
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