scholarly journals Growth Hormone Deficiency and Excess Alter the Gut Microbiome in Adult Male Mice

Endocrinology ◽  
2020 ◽  
Vol 161 (4) ◽  
Author(s):  
Elizabeth A Jensen ◽  
Jonathan A Young ◽  
Zachary Jackson ◽  
Joshua Busken ◽  
Edward O List ◽  
...  

Abstract The gut microbiome has been implicated in host metabolism, endocrinology, and pathophysiology. Furthermore, several studies have shown that gut bacteria impact host growth, partially mediated through the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis. Yet, no study to date has examined the specific role of GH on the gut microbiome. Our study thus characterized the adult gut microbial profile and intestinal phenotype in GH gene-disrupted (GH-/-) mice (a model of GH deficiency) and bovine GH transgenic (bGH) mice (a model of chronic, excess GH action) at 6 months of age. Both the GH-/- and bGH mice had altered microbial signatures, in opposing directions at the phylum and genus levels. For example, GH-/- mice had significantly reduced abundance in the Proteobacteria, Campylobacterota, and Actinobacteria phyla, whereas bGH mice exhibited a trending increase in those phyla compared with respective controls. Analysis of maturity of the microbial community demonstrated that lack of GH results in a significantly more immature microbiome while excess GH increases microbial maturity. Several common bacterial genera were shared, although in opposing directions, between the 2 mouse lines (e.g., decreased in GH-/- mice and increased in bGH mice), suggesting an association with GH. Similarly, metabolic pathways like acetate, butyrate, heme B, and folate biosynthesis were predicted to be impacted by GH. This study is the first to characterize the gut microbiome in mouse lines with altered GH action and indicates that GH may play a role in the growth of certain microbiota thus impacting microbial maturation and metabolic function.

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Elizabeth Ann Jensen ◽  
Zachary Jackson ◽  
Jonathan Alan Young ◽  
Jaycie Kuhn ◽  
Maria Onusko ◽  
...  

Abstract Emerging evidence proposes that the gut microbiome has an vital role in host growth, metabolism and endocrinology. That is, gut microbes impact growth by potentially altering the growth hormone (GH)/insulin-like growth factor-1 axis. Our previous research has also shown that GH - in states of absence and excess - is associated with altered gut microbial composition, maturity and predictive metabolic function in mice. Moreover, both GH and the gut microbiome are implicated in development and aging. Yet, it is unknown how GH impacts the longitudinal microbiome. This study thus aimed to characterize the longitudinal changes in the gut microbial profile of bovine GH transgenic mice (a model of chronic, excess GH action and accelerated aging). Microbial composition was quantified from fecal pellets of the same bGH and control mice at 3, 6 and 12 months of age through 16S rRNA gene sequencing and QIIME 2. Additional bioinformatic analyses assessed the unique signature and predictive metabolic function of the microbiome. The bGH mice had a distinct microbial profile compared to controls longitudinally. At 3 months, bGH mice had increased Firmicutes and Actinobacteria, decreased Bacteroidetes, Proteobacteria and Campylobacterota, and a significant reduction in microbial richness and evenness. By 6 months, all of the aforesaid phyla were increased with the exception of Firmicutes. By 12 months, bGH mice exhibited dysbiosis with increased Firmicutes and Proteobacteria and reduced Bacteroidetes, microbial richness and evenness. Moreover, abundance in Firmicutes, Bacteroidetes and Campylobacterota were significantly explained by the combined effect of genotype and age (p = 0.006, 0.005 and 0.02, respectively). Across all timepoints, bGH mice had a significantly different microbiome compared to controls (p = 0.002), and the development of microbial richness and evenness were also significantly different in bGH mice (p = 0.034 and 0.023). Bacterial genera Lactobacillus, Ruminococcaceae and Lachnospiraceae were identified as a unique candidates in bGH mice across all timepoints. Likewise, metabolic pathways involved in biosynthesis of heme b, menaquinol, acetate and butyrate differentiated the longitudinal bGH microbiome. Collectively, these results show that chronic, excess GH impacts the development and aging of the gut microbiome. Notably, several of the stated bacterial genera and metabolic pathways were associated with GH in our previous study, suggesting that GH may influence the longitudinal presence of certain gut microbes and metabolic functions. Additional studies will be performed to further explore the GH-associated gut microbiome and its impact on host health. Research was partially funded by the John J. Kopchick MCB/TBS Fellowship, a fellowship from the Osteopathic Heritage Foundation and the MMPC at UC, Davis (NIH grant U240DK092993).


2011 ◽  
Vol 1 (3) ◽  
pp. 174-182 ◽  
Author(s):  
Diptesh Gupta ◽  
Michael Gardner ◽  
Adam Whaley-Connell

2021 ◽  
Vol 22 (15) ◽  
pp. 7800
Author(s):  
Sally Temraz ◽  
Farah Nassar ◽  
Firas Kreidieh ◽  
Deborah Mukherji ◽  
Ali Shamseddine ◽  
...  

Disruptions in the human gut microbiome have been associated with a cycle of hepatocyte injury and regeneration characteristic of chronic liver disease. Evidence suggests that the gut microbiota can promote the development of hepatocellular carcinoma through the persistence of this inflammation by inducing genetic and epigenetic changes leading to cancer. As the gut microbiome is known for its effect on host metabolism and immune response, it comes as no surprise that the gut microbiome may have a role in the response to therapeutic strategies such as immunotherapy and chemotherapy for liver cancer. Gut microbiota may influence the efficacy of immunotherapy by regulating the responses to immune checkpoint inhibitors in patients with hepatocellular carcinoma. Here, we review the mechanisms by which gut microbiota influences hepatic carcinogenesis, the immune checkpoint inhibitors currently being used to treat hepatocellular carcinoma, as well as summarize the current findings to support the potential critical role of gut microbiome in hepatocellular carcinoma (HCC) immunotherapy.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Elizabeth Jensen ◽  
Zachary Jackson ◽  
Joshua Busken ◽  
Jonathan Young ◽  
Jaycie Kuhn ◽  
...  

PEDIATRICS ◽  
1981 ◽  
Vol 68 (2) ◽  
pp. 260-264
Author(s):  
Stephen LaFranchi ◽  
Neil R. M. Buist ◽  
Banoo Jhaveri ◽  
Harvey Klevit

In order to investigate the role of amino acid (AA) substrates in the hypoglycemia associated with human growth hormone (hGH) deficiency, we measured 12-hour fasting blood glucose and total quantitative AA concentrations in 11 children with hGH deficiency during three study periods: (1) before hGH replacement; (2) after 12 months of hGH treatment; and (3) after discontinuation of hGH for three months. The results were compared to studies in 16 control subjects. Fasting blood glucose concentrations were significantly (P < .05) lower in the hGH-deficient children prior to hGH treatment as compared to the control subjects (67.0 ± 5.3 vs 80.7 ± 5.3 mg/100 ml, X ± SE). Fasting total serum AA concentrations were similar in the patients and in the control subjects; however, after 12 months of hGH replacement, there was a significant (P < .01) elevation of serum AA (2,750 ± 170 vs 2,283 µmoles/liter). Fasting serum concentrations of alanine, glycine, arginine, and tryptophan were also significantly elevated (P < .01) with hGH treatment; ornithine, tyrosine, lysine, methionine, and phenylalanine showed lesser elevations (P < .05), whereas threonine decreased significantly (P < .01). The fasting hypoglycemia seen with isolated hGH deficiency is not an AA substrate-limited disorder. The finding of increased concentrations of AA with hGH replacement suggests increased retention of nitrogen and synthesis of AA or a decreased requirement of AA for gluconeogenesis due to availability of other substrates.


Sign in / Sign up

Export Citation Format

Share Document