Gut Microbes to the Rescue: Probiotics Shield Kidneys and Sperm From E. coli Damage in Rats

Escherichia coli is best known as a gut dweller, but when it escapes into the urinary and reproductive tracts it becomes one of the most damaging bacterial pathogens in medicine. Urinary tract infections caused by E. coli are among the most common bacterial illnesses worldwide, and in men recurrent infections are closely linked to declining fertility. With antibiotic resistance eroding the reliability of standard therapy, researchers are increasingly turning to the body’s own microbial allies for answers. A new study published in Veterinary Medicine and Science now offers some of the most systematic evidence yet that Lactobacillus-based probiotics and their nonviable derivatives, known as postbiotics, can defend both kidneys and testes against E. coli–induced injury.

The research team, working at Islamic Azad University’s Central Tehran Branch in collaboration with Shahid Beheshti University, set out to fill a conspicuous gap in the literature. Although Lactobacillus strains have long been associated with protective effects in the female genitourinary tract, their potential to safeguard male reproductive health under active bacterial challenge had never been rigorously tested in a controlled experimental model. The investigators designed a study using a native Iranian probiotic and postbiotic formulation containing three strains: Lactobacillus casei, Lactobacillus rhamnosus, and Lactobacillus helveticus. Their goal was to assess whether these interventions could protect renal integrity, testicular function, and sperm quality in rats experimentally infected with E. coli.

The experimental design was straightforward but comprehensive. Twenty-eight adult male Wistar rats, each weighing between 200 and 250 grams, were acclimatized for one week under controlled conditions of a 12-hour light-dark cycle and an ambient temperature of 23 degrees Celsius. The animals were then divided into four groups: an uninfected control group, a group infected orally with E. coli at a concentration of 10 to the eighth colony-forming units per millilitre for three consecutive days, and two infected groups that subsequently received either the probiotic mixture or the postbiotic preparation by daily oral gavage for 35 days. The postbiotic was prepared by culturing the probiotic powder, centrifuging the suspension, and filtering it through a 0.22-micrometre membrane to obtain cell-free metabolites, ensuring that no living bacteria remained in that treatment arm.

The results were striking. Histopathological examination of kidney tissue revealed that infected rats suffered severe damage, including vacuolar degeneration of tubular cells, extensive haemorrhage, collagen fibre deposition, cellular necrosis, and dense lymphocyte infiltration. Periodic acid–Schiff staining, which highlights basement membrane integrity, confirmed the extent of the injury. In contrast, rats treated with either probiotics or postbiotics showed markedly attenuated pathology, with reduced vacuolization, diminished inflammatory infiltration, and improved glomerular structure. Three blinded pathologists independently scored the sections, achieving an inter-observer agreement coefficient of 0.82, which lends considerable statistical weight to the visual findings.

The testes told a parallel story. Infection caused a significant drop in testicular weight and volume, shrank the diameter of seminiferous tubules from roughly 243 micrometres in controls to 173 micrometres in infected animals, and thinned the germinal epithelium that houses developing sperm cells. The lumen of the tubules, meanwhile, expanded abnormally, a hallmark of germ cell loss. Probiotic and postbiotic supplementation partially reversed these changes: tubule diameter recovered to around 212 to 214 micrometres, germ cell layer thickness rebounded from 149 to roughly 244 to 250 micrometres, and testicular weight climbed back toward control values. Sperm analysis reinforced the pattern, with infected rats showing reduced sperm counts, impaired viability, and abnormal morphology, all of which improved modestly with either treatment.

Blood chemistry provided further evidence of renal protection. Serum urea and creatinine, two classic markers of kidney dysfunction, rose sharply in infected rats compared with controls. Treatment with probiotics or postbiotics significantly lowered both markers relative to the infected group, with creatinine reductions reaching statistical significance at the p less than 0.01 level. Serum potassium followed a similar trend, while sodium concentrations remained unchanged across all groups, indicating that the interventions did not disturb electrolyte homeostasis. These biochemical improvements aligned closely with the histological recovery observed under the microscope.

At the molecular level, the researchers used real-time polymerase chain reaction to quantify the expression of genes governing apoptosis and inflammation. Infection drove a significant upregulation of Bax, a pro-apoptotic gene, alongside elevated expression of the inflammatory cytokines tumour necrosis factor-alpha and interleukin-6 in both kidney and testicular tissue. The anti-apoptotic gene Bcl-2, by contrast, was suppressed. Probiotic and postbiotic treatment flipped this profile: Bax, TNF-alpha, and IL-6 expression fell dramatically compared with infected animals, while Bcl-2 rose significantly. The authors interpret this dual modulation of apoptotic and inflammatory pathways as the central mechanism by which the interventions preserved tissue integrity.

Antioxidant capacity emerged as another critical piece of the puzzle. Total antioxidant capacity in both kidney and testicular tissue was significantly depleted by infection, reflecting the oxidative stress that bacterial pathogens impose on host cells. Supplementation restored these values substantially, with postbiotic-treated animals even showing a modest, though not statistically significant, increase above control levels in kidney tissue. This restorative effect on antioxidant defences likely complements the anti-inflammatory and anti-apoptotic actions, since reactive oxygen species and inflammatory signalling reinforce one another in a vicious cycle that probiotic metabolites appear able to interrupt.

The mechanisms behind these effects are consistent with a growing body of microbiome research. Lactobacillus strains produce lactic acid, hydrogen peroxide, and bacteriocins that directly inhibit pathogenic colonization, while reinforcing epithelial barrier function and modulating toll-like receptor signalling, dendritic cell activity, and cytokine production. Postbiotics, comprising proteins, lipids, short-chain fatty acids, and other fermentation products, deliver many of these benefits without the logistical and safety concerns associated with live microorganisms, which is particularly relevant for immunocompromised patients. The multi-strain approach used here may also amplify protection, as prior studies suggest that combining strains with diverse metabolic and immunomodulatory properties produces synergistic effects.

The authors are careful to note that recovery was partial rather than complete, and that the study was conducted in a rodent model with a defined bacterial challenge rather than the complex, recurrent infections seen in clinical practice. Dose optimization, strain selection, timing of administration, and long-term safety evaluation all remain open questions before such interventions can be recommended for human use. Nevertheless, the findings add meaningful weight to the argument that microbiota-based therapies could serve as adjuncts or alternatives to antibiotics at a moment when antimicrobial resistance is escalating globally. If the protective effects observed in these rats translate to humans, a simple mixture of Lactobacillus strains or their metabolites might one day help men preserve both kidney function and fertility in the face of one of medicine’s most persistent bacterial adversaries.

Subject of Research: Protective effects of Lactobacillus-derived probiotics and postbiotics on renal and reproductive function in E. coli-infected rats

Article Title: Protective Effects of Lactobacillus‐Derived Probiotics and Postbiotics on Renal and Reproductive Function in Escherichia coli–Infected Rats

Article References: Sedghi, S., Keshtmand, Z., & Hosseini, S. (2026). Protective Effects of Lactobacillus ‐Derived Probiotics and Postbiotics on Renal and Reproductive Function in Escherichia coli –Infected Rats. Veterinary Medicine and Science, 12(6), Article e71258. https://doi.org/10.1002/vms3.71258

Image Credits: AI Generated

DOI: 10.1002/vms3.71258

Keywords: probiotics, postbiotics, Lactobacillus, Escherichia coli, urinary tract infection, male infertility, kidney injury, testicular function, sperm quality, oxidative stress, apoptosis, antimicrobial resistance