25-hydroxycholecalciferol reverses heat induced alterations in bone quality in finisher broilers associated with effects on intestinal integrity and inflammation

Huaiyong Zhang,Keying Zhang,George Daube,Bernard Taminiau,Joris Michiels,Djoere Gaublomme,Dirk Elewaut,Iván Josipovic,Maryam Majdeddin,Matthieu Boone

doi:10.1186/s40104-021-00627-6

Abstract

BackgroundAlterations in ambient temperature have been associated with multiple detrimental effects on broilers such as intestinal barrier disruption and dysbiosis resulting in systemic inflammation. Inflammation and 25-hydroxycholecalciferol (25-OH-D3) have shown to play a negative and positive role, respectively, in the regulation of bone mass. Hence the potential of 25-OH-D3 in alleviating heat induced bone alterations and its mechanisms was studied.ResultsHeat stress (HS) directly induced a decrease in tibia material properties and bone mass, as demonstrated by lower mineral content, and HS caused a notable increase in intestinal permeability. Treatment with dietary 25-OH-D3 reversed the HS-induced bone loss and barrier leak. Broilers suffering from HS exhibited dysbiosis and increased expression of inflammatory cytokines in the ileum and bone marrow, as well as increased osteoclast number and activity. The changes were prevented by dietary 25-OH-D3 administration. Specifically, dietary 25-OH-D3 addition decreased abundance of B- and T-cells in blood, and the expression of inflammatory cytokines, especially TNF-α, in both the ileum and bone marrow, but did not alter the diversity and population or composition of major bacterial phyla. With regard to bone remodeling, dietary 25-OH-D3 supplementation was linked to a decrease in serum C-terminal cross-linked telopeptide of type I collagen reflecting bone resorption and a concomitant decrement in osteoclast-specific marker genes expression (e.g. cathepsin K), whereas it did not apparently change serum bone formation markers during HS.ConclusionsThese data underscore the damage of HS to intestinal integrity and bone health, as well as that dietary 25-OH-D3 supplementation was identified as a potential therapy for preventing these adverse effects.

Highlights

Heat stress (HS) is well documented to have a negative influence on livestock productivity and climate change may exacerbate the incidence of HS
It has been reported that HS directly affects gut integrity and induces the activation of the innate immune system resulting in systemic inflammation in bovine [10], rats [11], and laying hens [12]
Germ-free mice were showing a reduced number of osteoclasts and lower level of Interleukin (IL)-6, receptor activator of nuclear factor-κ B ligand (RANKL), tumor necrosis factor alpha (TNFα), and CD4+T cells in bone [18, 19]. These features were normalized by colonization with gut microbiota from conventionally raised mice [19]. This suggests that the interaction between gut microbiota and the immune system may play a significant role in bone metabolism [9]

Summary

Results

The outcome of inflammation analysis revealed that the mRNA levels of proinflammatory factors, including IL-1β, IL-6, and TNF-α, were increased in the ileum of HS birds compared with Ctrl and/or PF broilers (P < 0.05). Abundances of pro-inflammatory factors were correspondingly modulated by dietary 25-OH-D3 treatment, i.e. IL-1β and TNF-α expression in ileum were remarkably suppressed by 25-OH-D3 supplementation while a trend for higher mRNA abundance of TGF-β was seen (P = 0.078) (Fig. 5D). As far as osteoclastogenesis-related factors in bone, HS increased the expression level of RANKL (P < 0.01) and did not change osteoprotegerin (OPG) mRNA abundance, and notably increased RANKL-to-OPG ratio when compared to Ctrl or PF groups (P < 0.05). Dietary 25-OH-D3 treatment elevated the expression level of VDR, and notably increased OPG mRNA expression, and decreased RANKL-to-OPG ratio relative to HS broilers (Fig. 6C; P < 0.05).

Introduction

Materials and methods

Discussion

Conclusion