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丁酸盐给药不足以改善抗逆转录病毒治疗的 SIV 感染猕猴的免疫重建。

Butyrate administration is not sufficient to improve immune reconstitution in antiretroviral-treated SIV-infected macaques.

机构信息

Barrier Immunity Section, Laboratory of Viral Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.

Viral Immunity and Pathogenesis Unit, Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD, 20892, USA.

出版信息

Sci Rep. 2022 May 6;12(1):7491. doi: 10.1038/s41598-022-11122-x.

DOI:10.1038/s41598-022-11122-x
PMID:35523797
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9076870/
Abstract

Defective gastrointestinal barrier function and, in turn, microbial translocation have been identified as significant contributors to persistent inflammation in antiretroviral (ARV)-treated people living with HIV. Metabolic supplementation of short-chain fatty acids (SCFAs), generally produced by the commensal microbiome, may improve these outcomes. Butyrate is a SCFA that is essential for the development and maintenance of intestinal immunity and has a known role in supporting epithelial integrity. Herein we assessed whether supplementation with the dietary supplement sodium butyrate would improve immune reconstitution and reduce inflammation in ARV-treated, simian immunodeficiency virus (SIV)-infected rhesus macaques. We demonstrate that butyrate supplementation does not significantly improve immune reconstitution, with no differences observed in systemic CD4+ T-cell frequencies, T-cell functionality or immune activation, microbial translocation, or transcriptional regulation. Our findings demonstrate that oral administration of sodium butyrate is insufficient to reduce persistent inflammation and microbial translocation in ARV-treated, SIV-infected macaques, suggesting that this therapeutic may not reduce co-morbidities and co-mortalities in treated people living with HIV.

摘要

胃肠道屏障功能缺陷,进而导致微生物易位,被认为是导致抗逆转录病毒(ARV)治疗的 HIV 感染者持续炎症的重要因素。短链脂肪酸(SCFAs)的代谢补充,通常由共生微生物组产生,可能改善这些结果。丁酸盐是一种 SCFA,对肠道免疫的发育和维持至关重要,并且已知在支持上皮完整性方面发挥作用。在此,我们评估了膳食补充剂丁酸钠补充是否会改善 ARV 治疗的、感染猴免疫缺陷病毒(SIV)的恒河猴的免疫重建并减少炎症。我们证明,丁酸盐补充并没有显著改善免疫重建,全身 CD4+T 细胞频率、T 细胞功能或免疫激活、微生物易位或转录调节均无差异。我们的研究结果表明,口服丁酸钠不足以减少 ARV 治疗的、感染 SIV 的猕猴中的持续炎症和微生物易位,这表明该治疗方法可能无法降低接受治疗的 HIV 感染者的合并症和死亡率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/870a/9076870/357758fe88e7/41598_2022_11122_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/870a/9076870/7fada8b4b315/41598_2022_11122_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/870a/9076870/25fcd530d088/41598_2022_11122_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/870a/9076870/b5d8f24b4bfb/41598_2022_11122_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/870a/9076870/357758fe88e7/41598_2022_11122_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/870a/9076870/7fada8b4b315/41598_2022_11122_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/870a/9076870/25fcd530d088/41598_2022_11122_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/870a/9076870/b5d8f24b4bfb/41598_2022_11122_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/870a/9076870/357758fe88e7/41598_2022_11122_Fig4_HTML.jpg

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