Epigenetic changes in poultry due to reprogramming of the gut microbiota

Dietary fibre is fermented by the gut microbiota and protects against the development of cardiovascular disease (CVD) through the production of gut microbial metabolites. We hypothesised dietary fibre intake during pregnancy may prevent the development of CVD in the offspring via in utero epigenetic mechanisms. To investigate this, we fed C57BL/6J female mice diets high or low in resistant starches (‘high-fibre’ and ‘low-fibre’, respectively) during gestation. At 6-weeks of age, we performed single-cell RNA-sequencing in the offspring (n=8/group) or they were challenged with saline (sham) or angiotensin II (Ang II, 0.25mg/kg/day, n=18-23/group). Maternal diet resulted in a distinct gut microbial composition ( P =0.001). This was still evident in the adult offspring, with high-fibre offspring having a different gut microbial colonisation ( P =0.001), irrespective of sham/Ang II treatment. Maternal fibre intake significantly changed the cardiac cellular and molecular landscape and promoted differential gene signatures in the offspring. This included upregulation of genes associated with extracellular matrix production in the offspring from low-fibre mothers. When challenged with Ang II, low-fibre offspring developed increased cardiac hypertrophy ( P =0.034) and fibrosis ( P =0.01) compared to high-fibre offspring. This was accompanied with decreased ejection fraction ( P =0.001) and increased left ventricular posterior wall thickness ( P= 0.017). These changes were independent of blood pressure. High-fibre offspring had decreased expression of natriuretic peptides ( Nppa , P =0.03, Nppb , P =0.002) compared to low-fibre offspring. Chromatin-immunoprecipitation assay revealed decrease in H3-acetylation at the cis-regulatory region of Nppa gene in Ang II-treated high-fibre offspring (P=0.002), suggesting that maternal fibre intake influences the epigenetic changes of the Nppa gene in the offspring’s heart. Together, these data reveal maternal high-fibre intake leads to foetal epigenetic reprogramming, likely through maternal to foetal transfer of gut microbial-derived metabolites.

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Dietary metabolites derived from gut microbiota: critical modulators of epigenetic changes in mammals

Nutrition Reviews ◽

10.1093/nutrit/nux001 ◽

2017 ◽

Vol 75 (5) ◽

pp. 374-389 ◽

Cited By ~ 67

Author(s):

Mohd Iqbal Bhat ◽

Rajeev Kapila

Keyword(s):

Gut Microbiota ◽

Epigenetic Changes

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Review for "Gut microbiota alterations affect glioma growth and innate immune cells involved in tumor immunosurveillance in mice"

10.1002/eji.201948354/v2/review1 ◽

2020 ◽

Keyword(s):

Gut Microbiota ◽

Immune Cells ◽

Innate Immune ◽

Innate Immune Cells ◽

Tumor Immunosurveillance ◽

Glioma Growth

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Decision letter for "Gut microbiota alterations affect glioma growth and innate immune cells involved in tumor immunosurveillance in mice"

10.1002/eji.201948354/v2/decision1 ◽

2020 ◽

Keyword(s):

Gut Microbiota ◽

Immune Cells ◽

Innate Immune ◽

Innate Immune Cells ◽

Tumor Immunosurveillance ◽

Glioma Growth

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Review for "Gut microbiota alterations affect glioma growth and innate immune cells involved in tumor immunosurveillance in mice"

10.1002/eji.201948354/v1/review2 ◽

2019 ◽

Keyword(s):

Gut Microbiota ◽

Immune Cells ◽

Innate Immune ◽

Innate Immune Cells ◽

Tumor Immunosurveillance ◽

Glioma Growth

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Review for "Gut microbiota alterations affect glioma growth and innate immune cells involved in tumor immunosurveillance in mice"

10.1002/eji.201948354/v1/review1 ◽

2019 ◽

Keyword(s):

Gut Microbiota ◽

Immune Cells ◽

Innate Immune ◽

Innate Immune Cells ◽

Tumor Immunosurveillance ◽

Glioma Growth

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Folate and vitamin B-12 deficiencies additively impaired memory function and disturbed the gut microbiota in amyloid-β infused rats

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000624 ◽

2019 ◽

pp. 1-13 ◽

Cited By ~ 2

Author(s):

Sunmin Park ◽

Sunna Kang ◽

Da Sol Kim

Keyword(s):

Insulin Resistance ◽

Gut Microbiota ◽

Insulin Signaling ◽

Gut Microbiome ◽

Metabolic Diseases ◽

Memory Function ◽

Amyloid Β ◽

Impaired Memory ◽

Ca1 Region ◽

Folate And Vitamin B12

Abstract. Folate and vitamin B12(V-B12) deficiencies are associated with metabolic diseases that may impair memory function. We hypothesized that folate and V-B12 may differently alter mild cognitive impairment, glucose metabolism, and inflammation by modulating the gut microbiome in rats with Alzheimer’s disease (AD)-like dementia. The hypothesis was examined in hippocampal amyloid-β infused rats, and its mechanism was explored. Rats that received an amyloid-β(25–35) infusion into the CA1 region of the hippocampus were fed either control(2.5 mg folate plus 25 μg V-B12/kg diet; AD-CON, n = 10), no folate(0 folate plus 25 μg V-B12/kg diet; AD-FA, n = 10), no V-B12(2.5 mg folate plus 0 μg V-B12/kg diet; AD-V-B12, n = 10), or no folate plus no V-B12(0 mg folate plus 0 μg V-B12/kg diet; AD-FAB12, n = 10) in high-fat diets for 8 weeks. AD-FA and AD-VB12 exacerbated bone mineral loss in the lumbar spine and femur whereas AD-FA lowered lean body mass in the hip compared to AD-CON(P < 0.05). Only AD-FAB12 exacerbated memory impairment by 1.3 and 1.4 folds, respectively, as measured by passive avoidance and water maze tests, compared to AD-CON(P < 0.01). Hippocampal insulin signaling and neuroinflammation were attenuated in AD-CON compared to Non-AD-CON. AD-FAB12 impaired the signaling (pAkt→pGSK-3β) and serum TNF-α and IL-1β levels the most among all groups. AD-CON decreased glucose tolerance by increasing insulin resistance compared to Non-AD-CON. AD-VB12 and AD-FAB12 increased insulin resistance by 1.2 and 1.3 folds, respectively, compared to the AD-CON. AD-CON and Non-AD-CON had a separate communities of gut microbiota. The relative counts of Bacteroidia were lower and those of Clostridia were higher in AD-CON than Non-AD-CON. AD-FA, but not V-B12, separated the gut microbiome community compared to AD-CON and AD-VB12(P = 0.009). In conclusion, folate and B-12 deficiencies impaired memory function by impairing hippocampal insulin signaling and gut microbiota in AD rats.

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