Fertility is influenced by a wide range of biological and environmental factors in both women and men. Age, hormone regulation, lifestyle, infections, and genetic makeup all play important roles (1). Genetics, for example, determine the quality and quantity of eggs and sperm, the regulation of reproductive hormones, and the ability of embryos to develop normally. Certain genetic variants have been linked to reduced fertility or reproductive complications. For example, mutations affecting genes involved in ovarian function or spermatogenesis, such as FMR1, CFTR and Y-chromosome genes, have been associated with impaired fertility, while variants involved in folate metabolism, including MTHFR polymorphisms, have been investigated for associations with pregnancy outcomes such as recurrent pregnancy loss (2, 3). Alongside these established influences, research has begun to explore the role of the human microbiome.

In women, the vaginal and endometrial microbial communities are increasingly recognized as supportive for reproductive health (4, 5). When species of Lactobacillus dominate, they help maintain a protective acidic environment, reducing the risk of infections and creating conditions that may be more favourable for conception and pregnancy (6). However, it is important to emphasize that women with a range of microbial patterns can and do conceive and carry pregnancies successfully.

In men, sperm health is shaped by genetics, oxidative stress (an imbalance between reactive oxygen species and antioxidant defences that can damage sperm membranes and DNA), and lifestyle factors (for example, smoking, excessive alcohol, poor diet and environmental pollutants) (2, 7, 8). Emerging evidence suggests that the gut and reproductive tract microbiota may also contribute by influencing inflammation and hormone activity, factors that can affect sperm function and quality (9, 10).

Fertility is therefore best understood as the product of multiple interwoven factors. The microbiome is indeed a promising area of research within this broader landscape, but it should be considered one part of a much larger picture. The purpose of this review is to examine current evidence on the role of the gut and reproductive tract microbiomes in fertility and to evaluate the potential of probiotics, diet, and lifestyle factors as supportive strategies for reproductive health.

In women, a vaginal microbial community rich in Lactobacillus species is generally considered supportive for reproductive health. This type of microbial environment helps protect against infections and may play a role in creating favourable conditions for conception and early pregnancy (4,​​​​​​​ 6). Some studies have found associations between a more variable microbial environment and fertility challenges, but results are inconsistent, and it is not yet clear whether the microbiome itself plays a causal role (4, 11, 12).

In men, microbial communities in the gut and reproductive organs are thought to influence sperm quality by modulating inflammation and oxidative stress. For example, beneficial microbes may help to protect sperm through anti-inflammatory and antioxidative effects. While early associations have been described, this remains a developing field, and findings should be interpreted as exploratory (9, 13).

One of the most intriguing areas of current study is how the gut microbiota communicates with reproductive organs through biochemical “crosstalk.” Gut microbes can influence sex hormone metabolism, particularly oestrogens and androgens, by producing enzymes that recycle these hormones (14, 15). This means that an imbalanced gut microbiome may alter circulating hormone levels, potentially impacting ovulation in women and testosterone regulation in men.

In woman, beneficial microbes, such as Lactobacillus, produce lactic acid and antimicrobial compounds, which maintains a low vaginal pH, reducing infection risk and providing a more hospital environment for sperm (6, 16, 17). When the microbial balance shifts, inflammatory signals and enzyme activity may alter cervical mucus and uterine tissue (18, 19). For example, bacterial vaginosis–associated communities can be enriched with organisms like Gardnerella, Atopobium, or Prevotella, which may increase local immune responses. These microbes can stimulate pro-inflammatory cytokines and produce enzymes such as mucin-degrading proteases and sialidases, which may alter cervical mucus properties and disrupt epithelial barrier function in the reproductive tract (20–22). However, the strength and consistency of these effects on fertility outcomes are not yet fully understood (11).

In the gut, microbial metabolism can affect oestrogen recycling and availability (14, 23). Oestrogen is a key hormone for reproductive function, influencing endometrial receptivity and ovarian health (23). Oestrogens are metabolised in the liver and excreted into the intestine as conjugated metabolites. Certain intestinal bacteria produce β-glucuronidase enzymes that deconjugate oestrogen metabolites in the intestine, allowing them to be reabsorbed into circulation rather than excreted, thereby influencing systemic oestrogen availability (23). These subset of gut bacteria are often referred to as the estrobolome. This highlights how microbial activity in one part of the body may influence distant reproductive organs.

It is also worth noting that the vaginal microbiome can fluctuate throughout a woman’s life, during puberty, menstruation, pregnancy, and menopause (24, 25). Hormonal changes, sexual activity, and hygiene practices all influence microbial balance (26). For example, oestrogen promotes glycogen accumulation in vaginal epithelial cells. This glycogen is degraded in the vaginal lumen by host enzymes such as α-amylase into smaller sugars that can be metabolized by Lactobacillus species to produce lactic acid, thereby lowering vaginal pH and helping maintain a Lactobacillus-dominated microbiome. This illustrates why hormonal and microbial factors are closely interconnected in maintaining vaginal health (6, 27, 28).

In men, microbial dysbiosis may also influence fertility through inflammatory and oxidative pathways (7). Increased inflammatory signalling and production of reactive oxygen species can damage sperm membranes, impair motility, and affect DNA integrity, thereby reducing sperm quality (9). Systemic hormonal balance and adequate micronutrient status are also essential for normal sperm production (29, 30), suggesting that broader metabolic changes may contribute indirectly to reproductive outcomes.

Stress is also a factor that can influence fertility (31, 32). Through the hypothalamic pituitary adrenal (HPA) axis, stress increases cortisol, which can disrupt ovulation in women and impair sperm production in men (33). Chronic stress is also linked with inflammation and immune imbalances, which may affect reproductive tissues (34, 35).

The “gut–brain–reproductive axis” is an emerging concept describing how mental and emotional states can influence reproductive biology through the microbiome. By supporting microbial balance, probiotics may help modulate physiological stress responses through gut–brain signalling pathways. Changes in gut microbiota composition have been linked to altered production of microbial metabolites, inflammatory signalling, and regulation of the hypothalamic–pituitary–adrenal (HPA) axis, which influences cortisol levels and can affect hormone regulation (36–39). Reviews suggest that probiotics may modestly reduce perceived stress and cortisol levels (40, 41), though no study has yet linked this directly to improved fertility outcomes. This means that probiotics might support fertility indirectly by helping to regulate stress responses, but the evidence is preliminary.

Psychological wellbeing also influences relationship dynamics, sexual function, and adherence to lifestyle changes, all of which affect fertility. Recognizing the mind-body connection reinforces the idea that fertility care should not focus solely on biological interventions but should include holistic stress management and emotional support.

Diet can also influence systemic inflammation and reproductive health through multiple pathways (42). Dietary patterns that reduce inflammation, such as those rich in fruits, vegetables, and healthy fats, have been linked to improved fertility outcomes and lower inflammation in some populations (43, 44). Antioxidant-rich plant foods provide bioactives including polyphenols such as proanthocyanidins and flavonoids, as well as carotenoids and vitamin C, which can help counter oxidative stress and may be relevant to reproductive physiology (45). Prebiotic fibres and other fermentable substrates in foods including compounds such as inulin, fructo-oligosaccharides, and galacto-oligosaccharides, can be utilised by beneficial gut bacteria, increasing the production of short-chain fatty acids, which can modulate inflammatory signalling pathways (46, 47). Together, dietary nutrients and microbiota-mediated metabolism may help lower oxidative stress and inflammation in ways that are relevant to reproductive health (44, 48).

Clinical research on probiotics for women’s fertility is still limited, and results are mixed. Most of the available evidence comes from studies assessing outcomes that are indirectly linked to fertility, such as vaginal microbial balance, reduction of infections, and improvement in metabolic or hormonal health.

Species such as Lactobacillus crispatus, Lacticaseibacillus gasseri, Lactobacillus acidophilus, and Limosilactobacillus fermentum have been studied for their ability to support vaginal microbial balance. L. crispatus has been shown in randomized trials to reduce recurrence of bacterial vaginosis and is being investigated in pregnancy-related contexts (49, 50). Other probiotic strains, including Lacticaseibacillus rhamnosus GR-1 and Limosilactobacillus reuteri RC-14, have also been studied for the treatment of vaginal dysbiosis and bacterial vaginosis, with clinical trials demonstrating improved restoration of Lactobacillus-dominated vaginal microbiota (51, 52). L. gasseri CECT 30648 has demonstrated the ability to colonize the vagina after oral intake of 1 x 10⁹ CFU/capsule with peak colonisation observed between days six and fifteen (53), while L. acidophilus LA02 and L. fermentum LF10 have been studied using slow-release vaginal tablets (at 0.8 billion live cells per tablet) in women with recurrent vulvovaginal candidiasis, where supplementation reduced recurrence rates as part of a two phase prophylactic treatment (54). These findings suggest that certain Lactobacillus species can contribute to vaginal ecological stability, which may indirectly support reproductive health (55–57).

Several clinical studies have also evaluated probiotics in women undergoing assisted reproduction. Randomized and controlled trials have investigated Lactobacillus-based probiotics administered orally or intravaginally to women undergoing in vitro fertilization (IVF) with the aim of restoring Lactobacillus-dominant vaginal microbiota and reducing dysbiosis associated with implantation failure. While improvements in vaginal microbial composition have been reported in some studies, most trials have not demonstrated consistent improvements in pregnancy or live birth rates compared with control groups, highlighting the need for larger well-designed studies (12, 58).

One of the first human trials to evaluate a fertility outcome with an oral probiotic was a triple-blind, placebo-controlled study in couples with unexplained infertility preparing for in vitro fertilization. Supplementation with the probiotic strain Ligilactobacillus salivarius CECT5713 administered orally as one capsule daily (3 × 10⁹ viable cells per day) for approximately six months prior to IVF treatment and continued during the IVF cycle was associated with a higher rate of pregnancies resulting in live birth compared with placebo (59). In contrast, a large multinational randomized trial (the NiPPeR study) testing a combined formulation containing myo-inositol, probiotics (L. rhamnosus NCC 4007 and Bifidobacterium animalis subsp. lactis NCC 2818), and micronutrients in women trying to conceive naturally found no significant benefit for time-to-pregnancy, clinical pregnancy, or live birth compared with a control supplement (60). Importantly, the probiotics were administered as part of a multi-ingredient supplement, so the specific contribution of the probiotic strains cannot be determined.

Taken together, these studies suggest that probiotics may support reproductive health indirectly by improving microbial balance, reducing infection recurrence, or supporting hormonal regulation. Future probiotic research in women’s fertility may explore not only which bacterial species and strain are most effective, but also when they should be used, for example, whether certain phases of the menstrual cycle or stages of fertility treatment respond better to microbial support.

In men, most probiotic research has focused on semen quality rather than direct fertility or pregnancy outcomes. This line of research looks at whether probiotics can improve biological features of sperm that are essential for conception, such as how many are produced (sperm concentration), how effectively they swim (motility), how healthy they appear (morphology), and whether their genetic material remains undamaged (DNA integrity). Several controlled trials report that probiotic or synbiotic supplementation may improve these parameters of sperm health (61). For example, in a randomized double-blind pilot study involving men with idiopathic oligoasthenoteratospermia, supplementation with a synbiotic formulation containing 5 billion cells of Lacticaseibacillus paracasei B21060 together with prebiotic substrates for six months resulted in significant improvements in sperm concentration, progressive motility, morphology, and ejaculate volume compared with a control group (62). These improvements were accompanied by reductions in markers of oxidative stress, suggesting that modulation of the gut microbiota may influence reproductive physiology through metabolic and inflammatory pathways. However, most studies in this area involve relatively small sample sizes and focus primarily on semen parameters rather than clinical fertility outcomes. While probiotics may improve certain semen parameters, there is currently no consistent evidence from large-scale trials demonstrating improvements in conception or live birth outcomes following male supplementation (63).

Beyond semen quality, some probiotic species have been explored for their effects on urogenital health, as urogenital infections and inflammation are a significant etiologic factor in male infertility (64). L. paracasei CNCM I-1572 (Lactobacillus casei DG®) has been evaluated as an adjunct to antibiotic therapy in men with chronic bacterial prostatitis. In a phase IV clinical study, supplementation with the probiotic for three months following antibiotic treatment was associated with reduced symptom recurrence, improved symptom scores, and decreased antibiotic use compared with standard therapy alone (65). Probiotics may therefore be considered as possible supportive measures for male reproductive health.

Lifestyle factors strongly influence reproductive health. Diets rich in plant-based foods, fibre, and healthy fats support microbial stability and systemic health, while diets high in sugar and processed foods may increase inflammation (66,​​​​​​​ 67). Nutritional studies have shown that Mediterranean-style diets, rich in vegetables, fruits, legumes, whole grains, and omega-3 fatty acids, are associated with improved reproductive outcomes (68, 69). These diets naturally support beneficial gut bacteria such as Bifidobacterium, Lactobacillus, Faecalibacterium, and Roseburia, which ferment dietary fibres to produce anti-inflammatory metabolites including short-chain fatty acids such as acetate, propionate, and butyrate that help regulate immune and metabolic signalling (70). Adequate sleep is also essential.

Insufficient or poor-quality sleep disrupts circadian regulation of reproductive and metabolic hormones, including melatonin, cortisol, leptin, and ghrelin, which can alter appetite regulation, increase physiological stress, and affect ovulatory and metabolic function (71–73). Sleep disruption has also been associated with changes in gut microbiota composition, suggesting that sleep patterns may influence both microbial balance and reproductive health (74, 75). Supporting healthy lifestyle patterns, including balanced nutrition, adequate sleep, stress management, and physical activity, remains a cornerstone of fertility care for both women and men. Age, endocrine conditions such as PCOS or thyroid disorders, certain medications, and environmental exposures all play important roles. The microbiome should therefore be seen as one emerging contributor within a much larger network of factors that influence reproductive health.

Fertility challenges are deeply personal and emotionally difficult. Scientific research into the microbiome offers new insights, but this field is still developing. Probiotics may support reproductive health indirectly, through microbial balance, infection prevention, and metabolic or stress-related pathways. Future large-scale, independent randomized controlled trials will be essential to determine whether probiotics can meaningfully impact fertility outcomes. The most supportive approach combines lifestyle care, including nutrition, sleep, stress management, and medical guidance, with emerging science. The microbiome may ultimately become part of a more holistic approach to reproductive health and should be seen as a promising area of research.