Male fertility is usually discussed in terms of hormones, sperm count and reproductive anatomy. But emerging research suggests the gut may also be part of the picture.

A 2026 prospective cohort study looked at the gut microbiota in men with non-obstructive azoospermia (NOA) and asked whether microbiome patterns were associated with spermatogenic capacity and with the success of sperm retrieval during microdissection testicular sperm extraction, or micro-TESE.

The study included 39 men with azoospermia: 14 with obstructive azoospermia and 25 with non-obstructive azoospermia. The researchers identified distinct microbial patterns between the groups and, importantly, differences within the NOA group according to whether sperm could successfully be retrieved from the testes. The authors described these findings as exploratory and stressed that they require validation in larger cohorts.

This does not prove that the gut microbiome determines sperm production. Instead it raises an intriguing question: Could the intestinal microbiome influence the biological environment in which spermatogenesis takes place?

What is the gut–testis axis?

The concept of a gut–testis axis describes the possibility that the intestinal microbiome communicates with the male reproductive system through immune, metabolic and hormonal pathways.

Gut bacteria do far more than simply help digest food. They produce metabolites, interact with the immune system, influence intestinal barrier integrity and participate in metabolic and endocrine signalling.

The emerging model is therefore best understood as a chain of connected physiological effects:

microbiome → inflammation → oxidative stress → metabolic signalling → hormones → testicular environment → sperm production.

1. Microbiome

Changes in the composition and diversity of the gut microbiome can alter the metabolites produced in the intestine and affect the integrity of the gut barrier. Human research in men with non-obstructive azoospermia has already identified differences in microbial composition and microbial metabolic pathways compared with controls.

2. Inflammation

If intestinal barrier function becomes impaired, microbial products may gain greater access to the circulation and stimulate systemic immune activity. The testes, however, require a tightly regulated immune environment for normal sperm development. Developing germ cells are partly protected by the blood–testis barrier, and persistent inflammatory signalling may therefore influence the environment in which spermatogenesis occurs.

3. Oxidative stress

Inflammation and metabolic dysfunction can increase the production of reactive oxygen species.

Sperm are particularly vulnerable to oxidative damage because their membranes contain high concentrations of polyunsaturated fatty acids and their intrinsic antioxidant defences are relatively limited. Excessive oxidative stress may affect:

• sperm membranes
  
• mitochondrial function
  
• motility
  
• DNA integrity

A large meta-analysis has found significantly higher markers of oxidative stress and lower antioxidant capacity in seminal plasma from infertile men compared with controls.

4. Metabolic signalling

The microbiome also influences glucose regulation, lipid metabolism, bile-acid signalling and the production of metabolites such as short-chain fatty acids. If dysbiosis occurs alongside central obesity, insulin resistance or poor metabolic health, inflammatory and oxidative stress may increase further. This matters because the metabolic environment also influences reproductive endocrine function.

5. Hormonal signalling

Sperm production is controlled through the hypothalamic–pituitary–testicular axis, involving hormones including GnRH, LH, FSH and testosterone. The 2023 human microbiome study found associations between specific microbial patterns and clinical parameters including testosterone, FSH and BMI.

Although this does not tell us whether microbial changes altered hormone signalling, or hormonal changes affected the microbiome, or whether another metabolic factor influenced both, nonetheless it does reinforce the idea that the two systems are interconnected.

6. The testicular environment

The testes need a carefully controlled combination of hormonal signalling, nutrient availability, immune tolerance, vascular supply and oxidative balance.

Sertoli cells support developing germ cells, while Leydig cells produce testosterone. Both operate within this wider physiological environment. Changes in inflammation, oxidative stress, metabolism or endocrine signalling may therefore affect the conditions required for normal spermatogenesis.

7. Sperm production

If several of these disturbances occur together, the eventual result may be impaired spermatogenesis, poorer sperm quality or reduced reproductive capacity.

This does not mean that gut dysbiosis automatically causes infertility. It means that the microbiome may be one component of a wider physiological network influencing male reproductive function.

What have human studies found?

The 2026 study is particularly interesting because it did not simply compare fertile and infertile men. It compared men whose azoospermia resulted from an obstruction with men whose testes were failing to produce adequate sperm.

Compared with obstructive azoospermia, men with NOA showed differences in microbial composition, including reduced Bacteroidota and increased Proteobacteria. Within the NOA group itself, microbiome profiles also differed according to whether sperm could ultimately be retrieved during micro-TESE.

Earlier human work points in the same direction. A 2023 study using shotgun metagenomic sequencing found significant differences in gut microbial diversity and composition in men with NOA compared with healthy controls. Differences were also seen in microbial metabolic pathways, and some bacterial patterns were associated with testosterone, FSH and BMI.

Again, association does not prove causation, but taken together these studies suggest that severe male reproductive dysfunction may coexist with measurable changes in the intestinal ecosystem.

It may not only be the gut

Another developing area is the male reproductive microbiome itself. Microorganisms have been identified within semen and other parts of the reproductive tract, and altered microbial communities have been associated with impaired semen parameters and reproductive inflammation.

Rather than thinking about one isolated “fertility microbiome”, we may ultimately need to consider communication between the intestinal microbiome, systemic immune environment and reproductive tract microbiome. Sperm production does not occur in biological isolation.

What does this mean clinically?

The microbiome should not become another simplistic explanation for male infertility. Infertility can arise from genetic abnormalities, endocrine disorders, testicular injury, varicocele, infection, medication effects, environmental exposures, metabolic disease and many other causes. A man with impaired fertility therefore still requires an appropriate reproductive and medical assessment, but the emerging gut–testis research suggests that broader questions may also be relevant:

• How is his digestion?
• Are gastrointestinal symptoms persistent?
• What is his metabolic health like?
• Is insulin resistance or central adiposity present?
• How is he sleeping?
• Is chronic stress affecting endocrine or metabolic function?
• Is there a wider inflammatory or oxidative burden?

This does not replace conventional fertility investigation. It adds another layer to it.

How can herbal medicine fit into the gut–testis picture?

If the gut–testis axis is part of male reproductive health, treatment should not focus on sperm in isolation. The aim is not simply to increase sperm count, but to improve the wider physiological environment in which spermatogenesis takes place. This means looking at the individual as a whole — gut function, inflammation, oxidative balance, metabolism, stress and hormonal signalling — and selecting herbs according to the pattern that is actually present.

Herbal medicine can then be used to address the systems that appear most relevant in that individual case.

If digestive symptoms or signs of dysbiosis are present, we may consider herbs such as Cichorium intybus for its prebiotic support, or Althaea officinalis where the intestinal mucosa appears irritated or sensitive. Chicory-derived inulin-type fructans have been shown in human trials and meta-analysis to increase Bifidobacterium abundance, although these findings relate to gut ecology rather than fertility itself.

When oxidative stress is part of the picture, Camellia sinensis and Punica granatum may be considered for their polyphenol-rich antioxidant and anti-inflammatory actions.

Metabolic dysfunction may call for a different emphasis, with herbs such as Cinnamomum spp. or Gynostemma pentaphyllum selected to support glucose regulation and insulin sensitivity. Human clinical work with Gynostemma, for example, has shown improvements in glycaemia and insulin resistance in people with type 2 diabetes, although this evidence is metabolic rather than fertility-specific.

Where chronic stress, fatigue or poor recovery are affecting the wider picture, restorative and adaptogenic herbs such as Withania somnifera, Eleutherococcus senticosus or Panax ginseng may be considered.

Panax ginseng is particularly interesting in male fertility. In Traditional Chinese Medicine it has long been used within individualised formulas where reproductive weakness occurs alongside fatigue, depletion or reduced vitality. Modern research has begun to provide a physiological explanation for some of this traditional use. A randomized clinical trial in infertile men with varicocele reported improvements in several semen parameters with Korean red ginseng, while reviews suggest possible actions involving oxidative stress, inflammation and spermatogenic signalling. However, systematic review evidence remains limited and heterogeneous.

Withania somnifera has also been studied directly in male infertility. A systematic review found promising improvements in semen parameters, reproductive hormones and oxidative-stress markers, but the authors emphasised that the number and quality of available clinical trials were insufficient for firm conclusions.

The important point is that these herbs are not chosen simply because a patient has “low sperm count”. They are selected according to the wider physiological pattern that may be interfering with normal reproductive function.

Diet and the microbiome

Diet is one of the major influences on the intestinal microbial environment. A varied diet rich in vegetables, legumes, whole grains, berries, nuts, seeds and other sources of fermentable fibre and plant polyphenols provides substrates that support microbial diversity and microbial metabolism.

The dietary pattern may also influence male reproductive health more directly. A 2024 systematic review involving 2,032 men found that six of ten included studies reported a positive association between greater adherence to a Mediterranean-style diet and semen quality, particularly measures such as sperm concentration and motility.

A subsequent systematic review and meta-analysis involving 2,558 men also found positive associations between Mediterranean-diet adherence and several semen parameters, although evidence for pregnancy and assisted-reproduction outcomes remains considerably less certain.

The practical message is therefore not to search for one supposedly “fertility-enhancing” food.

It is to build a dietary environment rich in:

• plant diversity
  
• fermentable fibre
  
• polyphenols
  
• healthy fats
  
• whole foods

It is also addressing metabolic factors such as central obesity, insulin resistance, excessive alcohol intake, smoking, poor sleep and sedentary behaviour. The objective is to create an intestinal and metabolic environment that supports normal reproductive physiology.

What about probiotics?

This is an area of growing interest. Early studies suggest that selected probiotics and synbiotics may influence oxidative stress, inflammatory signalling and some semen parameters. But evidence remains preliminary. Different trials use different bacterial strains, doses and treatment periods, and an improvement in semen analysis does not necessarily mean improved conception or live-birth rates.

For now, probiotics are better viewed as a potentially useful tool in selected individuals rather than as an established treatment for male infertility.

The Clinical Insight

We have traditionally thought about male fertility largely through the reproductive system:

testes → hormones → sperm

The emerging research suggests a much broader network:

microbiome → inflammation → oxidative stress → metabolic signalling → hormones → testicular environment → sperm production

We are still at the beginning of understanding this relationship. The current evidence does not show that gut dysbiosis causes azoospermia, nor that altering the microbiome can reliably restore sperm production.

The finding that men with non-obstructive azoospermia have distinct gut microbial patterns — and that those patterns may even differ according to whether sperm can be retrieved from the testes — suggests that the gut–testis axis deserves much closer attention. Male fertility may prove to be another example of something we repeatedly observe in human physiology:

an organ rarely functions in isolation from the systems around it.

Wildberry Clinic | Men’s Health Series

Clinical herbal medicine grounded in science and individualised care.

This article is for educational purposes and does not replace individual medical or fertility assessment.

References

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8. Park HJ, Choe S, Park NC. Effects of Korean red ginseng on semen parameters in male infertility patients: a randomized, placebo-controlled, double-blind clinical study. Chinese Journal of Integrative Medicine. 2016;22(7):490–495. doi:10.1007/s11655-015-2139-9.
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