High-Fat Diet Induced Gut Microbiota Alterations Associating With Ghrelin/Jak2/Stat3 Up-Regulation to Promote Benign Prostatic Hyperplasia Development

Abstract

The role of high-fat diet (HFD) induced gut microbiota alteration and Ghrelin as well as their correlation in benign prostatic hyperplasia (BPH) were explored in our study. The gut microbiota was analyzed by 16s rRNA sequencing. Ghrelin levels in serum, along with Ghrelin and Ghrelin receptor in prostate tissue of mice and patients with BPH were measured. The effect of Ghrelin on cell proliferation, apoptosis, and induction of BPH in mice was explored. Our results indicated that BPH mice have the highest ratio of Firmicutes and Bacteroidetes induced by HFD, as well as Ghrelin level in serum and prostate tissue was significantly increased compared with control. Elevated Ghrelin content in the serum and prostate tissue of BPH patients was also observed. Ghrelin promotes cell proliferation while inhibiting cell apoptosis of prostate cells. The effect of Ghrelin on enlargement of the prostate was found almost equivalent to that of testosterone propionate (TP) which may be attenuated by Ghrelin receptor antagonist YIL-781. Ghrelin could up-regulate Jak2/pJak2/Stat3/pStat3 expression in vitro and in vivo. Our results suggested that Gut microbiota may associate with Ghrelin which plays an important role in activation of Jak2/Stat3 in BPH development. Gut microbiota and Ghrelin might be pathogenic factors for BPH and could be used as a target for mediation.

Alterations of gut microbiota diversity, composition and metabonomics in testosterone-induced benign prostatic hyperplasia rats

“…This suggests that the occurrence and development of BPH may be strongly correlated with the alteration of Bacteroidetes and Firmicutes . Another study has reported that gut microbiota may be associated with ghrelin which plays an important role in activation of JAK2/STAT3 in BPH development, indicating ghrelin might be pathogenic factors for BPH and could be used as a target for mediation [ 48 ]. As we all know, ghrelin is a gastric hormone which could be affected by metabolic syndrome.…”

The mechanism of Lingze tablets in the treatment of benign prostatic hyperplasia based on network pharmacology and molecular docking technology

“…JAK2/ STAT3 pathway is one of the important signal transduction pathways of various cytokines and growth factors in mammalian bodies. Gu et al found that it could promote prostatic gland and interstitial hyperplasia by activating JAK2/STAT3 pathway (Gu et al, 2021).…”

Gut Microbiota and Neonatal Acute Kidney Injury

“…80 On the other hand, gut dysbiosis, particularly an increased abundance of Firmicutes and Bacteroidetes, may upregulate ghrelin, thereby promoting cell proliferation and inhibiting apoptosis. 81 In addition, metabolites of gut microbiota such as SCFAs, amino acids, formyl peptides, lipopolysaccharides, and hydrogen sulfide regulate ghrelin in a direct or an indirect manner. 82 For example, SCFAs can attenuate ghrelin-mediated signals, such as ghrelin-dependent mobilization of intracellular calcium.…”