TRT Gut: How Testosterone Influences Your Microbiome

Testosterone replacement therapy (TRT) is commonly used to address low testosterone levels, but its effects extend beyond muscle growth and energy. Emerging research suggests it also influences gut health by altering microbiome composition, which plays a key role in digestion, immunity, and overall well-being.

Understanding how TRT affects gut bacteria could reveal potential benefits or unintended consequences for digestive and immune function.

Relationship Between TRT And Gut Microbial Diversity

TRT has been shown to alter gut microbiota, with studies indicating shifts in microbial diversity following hormone supplementation. Research published in Nature Communications (2021) found that testosterone levels correlate with bacterial population changes, particularly in individuals undergoing TRT for hypogonadism. These changes vary based on dosage, duration of therapy, and baseline microbiome composition. The gut microbiome, a complex ecosystem of bacteria, fungi, and archaea, plays a role in metabolic processes, and alterations in its diversity can impact nutrient absorption and gastrointestinal function.

One of the most notable findings is the shift in alpha and beta diversity, which measure species richness and community composition. A 2022 study in Frontiers in Endocrinology observed that men receiving TRT exhibited reduced microbial evenness, with certain bacterial taxa becoming more dominant while others declined. This suggests testosterone may create a selective environment favoring specific microbial groups. Bacteroides and Prevotella, genera associated with carbohydrate metabolism, have been reported to fluctuate in response to exogenous testosterone, potentially altering the gut’s ability to process dietary fibers and polysaccharides.

TRT also influences the balance between Firmicutes and Bacteroidetes, two major bacterial phyla linked to metabolic health. A higher Firmicutes-to-Bacteroidetes ratio has been associated with obesity, while a lower ratio is linked to lean body composition. Some studies suggest testosterone may promote a more favorable balance by increasing Akkermansia muciniphila, a bacterium known for maintaining gut barrier integrity and regulating metabolism. This could have implications for individuals using TRT to manage metabolic syndrome or age-related testosterone decline.

Mechanisms Influencing Gastrointestinal Environment

TRT affects the gastrointestinal environment through hormonal signaling, enzymatic activity, and gut motility. Androgen receptors (ARs), present in the intestinal lining, mediate testosterone’s influence on intestinal permeability, nutrient transport, and epithelial turnover. Androgens enhance gut barrier integrity by promoting tight junction proteins like occludin and zonula occludens-1 (ZO-1), which regulate intestinal wall permeability. This may reduce endotoxin translocation, a process where bacterial components like lipopolysaccharides (LPS) enter the bloodstream and contribute to systemic inflammation.

Testosterone also modulates bile acid metabolism, influencing microbial composition by selecting for bacteria capable of metabolizing these compounds. Research published in Cell Metabolism (2020) found that testosterone alters bile acid profiles, favoring bile salt hydrolase-producing species such as Lactobacillus and Bifidobacterium. These bacteria contribute to secondary bile acid formation, linked to improved lipid metabolism and reduced intestinal inflammation. Changes in bile acid composition may also impact short-chain fatty acid (SCFA) production, as some gut microbes use these compounds for energy and immune signaling.

Gut motility is another factor influenced by testosterone, with TRT often associated with changes in transit time and peristaltic activity. Androgens interact with the enteric nervous system (ENS), which governs intestinal contractions. A 2021 study in Neurogastroenterology & Motility reported that testosterone supplementation increases colonic transit speed, potentially affecting microbial fermentation patterns. Faster transit times may reduce fermentative bacteria proliferation, while slower motility can encourage the overgrowth of opportunistic species, influencing nutrient absorption and gut-brain signaling.

Key Bacterial Groups Under Testosterone

TRT reshapes the gut microbiome by favoring bacterial groups involved in energy metabolism and intestinal homeostasis. One of the most consistent shifts involves Akkermansia muciniphila, a mucin-degrading bacterium crucial for gut barrier function. Elevated testosterone levels have been associated with increased Akkermansia abundance, which may enhance mucosal integrity by stimulating mucus production and reducing gut permeability. This bacterium has also been linked to improved glucose metabolism, suggesting TRT-induced changes could extend beyond digestion.

Testosterone also affects the balance between Bacteroides and Prevotella, two genera involved in carbohydrate metabolism. Bacteroides, efficient degraders of polysaccharides, often become more dominant under TRT, potentially enhancing the breakdown of complex carbohydrates. Meanwhile, Prevotella, typically associated with high-fiber diets, has shown fluctuating trends in response to testosterone, which may influence the gut’s ability to ferment dietary fibers into SCFAs.

TRT impacts the Firmicutes-to-Bacteroidetes ratio, a commonly studied marker of gut composition. While a higher ratio has been linked to obesity, the specific taxa within these phyla are more relevant than the ratio alone. TRT has been shown to increase Faecalibacterium prausnitzii, a butyrate-producing bacterium with anti-inflammatory properties. Butyrate serves as a primary energy source for colonocytes and supports gut homeostasis by regulating pH and epithelial repair. The presence of Faecalibacterium may indicate a more favorable gut environment under TRT, potentially counteracting metabolic disturbances linked to hormonal imbalances.

Immune Response Alterations

TRT influences immune function by modulating cytokine production, immune cell differentiation, and inflammatory signaling. Androgens are known immunomodulators, affecting both innate and adaptive immune responses.

Testosterone suppresses pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β), which drive systemic inflammation. This suppression may lower baseline inflammation, benefiting individuals with chronic inflammatory conditions. At the same time, testosterone enhances anti-inflammatory cytokines like interleukin-10 (IL-10), which helps regulate immune balance and prevent excessive immune responses.

TRT also affects immune cell populations, particularly T cells and macrophages. Research suggests testosterone promotes regulatory T cell (Treg) differentiation, which helps suppress autoimmunity and maintain immune tolerance. This may explain why men, who generally have higher testosterone levels than women, exhibit lower rates of certain autoimmune disorders. However, testosterone’s immunosuppressive effects may also reduce immune vigilance, potentially increasing susceptibility to infections by dampening natural killer (NK) cell and macrophage activity.

Observations From Animal-Based Studies

Animal models have provided insights into testosterone’s influence on gut microbiota. Rodent studies have been particularly valuable in isolating its effects, as hormonal manipulation allows for controlled observations.

A study in The Journal of Endocrinology (2021) found that castrated male mice exhibited significant shifts in gut bacterial populations, with a reduction in Akkermansia muciniphila and an increase in pro-inflammatory bacteria like Desulfovibrio. When these mice were administered exogenous testosterone, their microbial profiles partially reverted, suggesting a direct relationship between androgen levels and bacterial balance. This shift coincided with improvements in gut barrier function, as measured by decreased intestinal permeability and lower circulating endotoxin levels.

Beyond microbial composition, animal studies highlight testosterone’s role in gut-derived metabolite regulation. Experiments on germ-free mice, which lack an intestinal microbiome, show that testosterone influences bile acid metabolism, indirectly selecting for bile-enriched bacteria. In testosterone-treated rats, researchers observed an increase in secondary bile acid-producing bacteria, which play a role in lipid digestion and metabolic regulation. Additionally, androgen administration has been linked to alterations in SCFA profiles, with increases in butyrate-producing species like Faecalibacterium prausnitzii. Given butyrate’s role in maintaining colonic health and reducing inflammation, these findings suggest testosterone may contribute to gut homeostasis by fostering a metabolically beneficial microbial environment.