3β-Hydroxysteroid dehydrogenase expressed by gut microbes degrades testosterone and is linked to depression in males

Di, Li; Liu, Ran; Wang, Ming; Peng, Rui; Fu, Shuai; Fu, Aisi; Le, Juan; Yao, Qian; Yuan, Tengfei; Chi, Haoming; Mu, Xin; Sun, Ting; Liu, Hang; Pan, Yan; Wang, Shao-Ting; Cheng, Shu; Deng, Zixin; Liu, Zhongchun; Wang, Gaohua; Li, Yan; Liu, Tiangang

doi:10.1016/j.chom.2022.01.001

Cited by 56 publications

(42 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, new therapeutic strategies are urgently required. In addition, the redox reactions of androgens occurring in the animal gut may alter circulating testosterone levels and thus lead to adverse effects on host physiology (Li et al, 2022). In the animal gut, which has a highly reducing environment, testosterone is often reduced to DHT, the most potent natural androgen (Colldén et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

“…In the animal gut, which has a highly reducing environment, testosterone is often reduced to DHT, the most potent natural androgen (Colldén et al, 2019). Therefore, gut microbes responsible for androgen reduction are often considered unfavorable species (Li et al, 2022). Our data indicate the possible applicability of androgen-catabolic gut bacteria as potent probiotics in alternative therapy of hyperandrogenism.…”

Section: Discussionmentioning

confidence: 99%

“…The deconjugated androgens, mainly testosterone and DHT, are present in the bacteria-rich colon of young men at concentrations much higher than those in the serum (Colldén et al, 2019). Most gut androgens (approximately 80%) are reabsorbed into the blood through enterohepatic circulation (Li et al, 2022; Sandberg and Slaunwhite, 1956).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Circulating androgen regulation by androgen-catabolizing gut bacteria in male mouse gut

Hsiao

Chou

Chen

et al. 2022

Preprint

View full text Add to dashboard Cite

SummaryAbnormally high circulating androgen levels have been considered a causative factor for benign prostatic hypertrophy and prostate cancer. Recent studies suggested that gut bacteria can alter sex steroid profile of host; however, the underlying mechanisms and bacterial taxa remain elusive. Thauera sp. strain GDN1 is an unusual betaproteobacterium capable of aerobic and anaerobic androgen catabolism in environmental conditions (37°C) resembling the mammalian gut. The strain GDN1 administration to C57BL/6J mice through oral gavage profoundly affected gut bacterial community, along with an approximately 50% reduction in serum androgen level in male mice. Our RT–qPCR results revealed the differential expression of aerobic and anaerobic androgen catabolic genes in the mouse ileum (microaerobic) and caecum (anaerobic), respectively. Furthermore, androgenic ring-cleaved metabolites were detected in the mouse fecal extract. This study discovered that androgen serves as a carbon source of gut microbes and that androgen-catabolizing gut bacteria can modulate host circulating androgen levels.HighlightsThauera sp. strain GDN1 administration through oral gavage regulated mouse serum androgen levels.The biochemical, genetic, and metabolite profile analyses revealed the occurrence of bacterial androgen catabolism in the mouse gut.Androgen catabolism proceeds through the O2-dependent and O2-independent catabolic pathways in mouse ileum and caecum, respectively.A possibility to harness Thauera sp. strain GDN1 as a functional probiotic to treat hyperandrogenism.Graphical AbstractIn briefHsiao et al. found that oral administration of androgen-catabolizing Thauera species regulated mouse serum androgen level. They characterized the gut microbe–mediated androgen catabolism through genetic and biochemical analyses. Their discovery portends a possibility of harnessing androgen-catabolic gut bacteria as functional probiotics to treat hyperandrogenism.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Circulating androgen regulation by androgen-catabolizing gut bacteria in male mouse gut

Hsiao

Chou

Chen

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Because 7α/β-dehydroxylation is restricted to free bile acids, deconjugation is a prerequisite. 7α/β-Hydroxysteroid dehydrogenases (7α/β-HSDHs) have been identified in gut bacteria such as Clostridium ( 116 – 118 ), Bacteroides ( 119 – 121 ), Escherichia ( 122 – 124 ) and Eubacterium ( 125 – 127 ). While 7α-dehydroxylation functions as the most quantitatively vital bacterial biotransformation of BAs, 7β-dehydroxylation appears to be not essential in the human colon ( 128 ).…”

Section: Relationship Between Gut Microbial Metabolites and T2dmmentioning

confidence: 99%

Gut microbiota: A new target for T2DM prevention and treatment

et al. 2022

View full text Add to dashboard Cite

Type 2 diabetes mellitus (T2DM), one of the fastest growing metabolic diseases, has been characterized by metabolic disorders including hyperglycemia, hyperlipidemia and insulin resistance (IR). In recent years, T2DM has become the fastest growing metabolic disease in the world. Studies have indicated that patients with T2DM are often associated with intestinal flora disorders and dysfunction involving multiple organs. Metabolites of the intestinal flora, such as bile acids (BAs), short-chain fatty acids (SCFAs) and amino acids (AAs)may influence to some extent the decreased insulin sensitivity associated with T2DM dysfunction and regulate metabolic as well as immune homeostasis. In this paper, we review the changes in the gut flora in T2DM and the mechanisms by which the gut microbiota modulates metabolites affecting T2DM, which may provide a basis for the early identification of T2DM-susceptible individuals and guide targeted interventions. Finally, we also highlight gut microecological therapeutic strategies focused on shaping the gut flora to inform the improvement of T2DM progression.

show abstract

“…65 Microbial expression of 3-β-hydroxysteroid dehydrogenase has also been linked to changes in mental health. 66 Furthermore, FMT from patients with depression to microbiotadeficient rats induced characteristic features of depression and alterations in tryptophan metabolism in the recipients. 65 Finally, a metaanalysis of 34 case-control studies found that perturbations of gut microbiota, including depletion of anti-inflammatory, and enrichment of pro-inflammatory bacteria, were associated with depression, bipolar disorder, anxiety, and schizophrenia.…”

mentioning

confidence: 99%

Updates in the Role of Pre- and Probiotics in Health and Disease: Where Do We Stand Today?

Humphry¹

2022

EMJ Gastroenterol

View full text Add to dashboard Cite

The 2022 International Scientific Conference of Probiotics, Prebiotics, Gut Microbiota and Health® took place in Bratislava, Slovakia, from 27th–30th June. A common theme throughout the conference was that, although significant progress has been made, considerable work remains to be done in understanding how probiotics work, aligning definitions of microbiome-modifying agents, and communicating evidence-based recommendations to clinicians and consumers. There was also an overarching concern around the ease with which food supplements receive marketing approval compared to drugs, and where probiotics lie on this spectrum. Arthur Ouwehand, International Flavors & Fragrances, Inc. (IFF), Kantvik, Finland, presented updates to the 2022 International Life Sciences Institute (ILSI) Concise Monograph on probiotics, prebiotics, and the gut microbiota in human health. Hania Szajewska, Medical University of Warsaw, Poland, focused on clinical recommendations for the use of probiotics, suggesting ways to approach the differences between guidelines. Regulatory agencies now recognise probiotics as a new category of medicinal products termed ‘live biotherapeutic products’, and Sin-Hyeog Im, Pohang University of Sciences and Biotechnology, Pohang, South Korea, and ImmunoBiome Inc., Pohang, South Korea, discussed the importance of characterising a new probiotic and understanding its mechanism of action to fulfil regulatory requirements. Benjamin Jensen, Department of Biomedical Sciences, University of Copenhagen, Denmark, stressed the importance of considering the gastrointestinal target and the diet and condition of the patient when developing probiotics, and Martin Haranta, PerBiotiX – Microbiome Solutions, Kysucké Nové Mesto, Slovakia, expanded on this subject, emphasising the promise that personalised and targeted modulation of gut microbiota holds for chronic disease. Sean Gibbons, Institute for Systems Biology, Seattle, Washington, USA, and University of Washington, Seattle, USA, described some of the current and emerging tools to support research into microbiota-based therapies and how these could be harnessed to achieve personalised medicine. Finally, links between the gut microbiome and the liver and central nervous system (CNS), and potential therapies to exploit these connections were illustrated by Peter Konturek, Thuringia-Clinic Saalfeld, Germany, and Gerard Clarke, University College Cork, Ireland.

show abstract

3β-Hydroxysteroid dehydrogenase expressed by gut microbes degrades testosterone and is linked to depression in males

Cited by 56 publications

References 43 publications

Circulating androgen regulation by androgen-catabolizing gut bacteria in male mouse gut

Circulating androgen regulation by androgen-catabolizing gut bacteria in male mouse gut

Gut microbiota: A new target for T2DM prevention and treatment

Updates in the Role of Pre- and Probiotics in Health and Disease: Where Do We Stand Today?

Contact Info

Product

Resources

About