Lactulose Improves Fecal Microflora in CKD Patients Original paper

What was studied?

This randomized clinical trial investigated how lactulose improves fecal microbiota composition in chronic kidney disease (CKD) and whether supplementation increases beneficial taxa depleted in CKD, particularly Bifidobacteria and Lactobacilli. The study directly examined whether an 8-week course of lactulose produces measurable microbiome changes and whether these shifts correspond with alterations in renal biomarkers, including serum creatinine and blood urea nitrogen (BUN). The investigators evaluated bacterial genera via anaerobic culturing, enabling quantification of colony-forming units before and after treatment. The study also assessed uremic waste products to contextualize microbiome changes within the metabolic environment characteristic of CKD. According to the results reported on page 1, lactulose produced a significant bifidogenic effect, increasing both Bifidobacteria and Lactobacilli counts compared with placebo.

Who was studied?

The trial included 32 adults with stage 3 or 4 CKD, randomized equally into lactulose and placebo groups. The patient population (mean age approximately 58 years, 43.8 percent male) was clinically stable and free from recent antibiotic exposure or medications affecting gut microbiota. Participants consumed 30 mL lactulose syrup three times daily or matching placebo for eight weeks. All baseline microbiome and clinical characteristics were comparable between groups, as shown in Table 1 on page 3. Patients adhered to standard diets but avoided fermented foods or prebiotics to minimize confounding influences on gut flora. Stool samples collected at baseline and week 8 were processed under anaerobic conditions and cultured on selective media to quantify Bifidobacteria and Lactobacilli (pages 2–3). Importantly, no participants withdrew, and lactulose was well tolerated with no report of major gastrointestinal adverse events.

Most important findings

The most notable finding was the significant enrichment of beneficial taxa, consistent with known dysbiotic signatures of CKD characterized by reduced SCFA-producing organisms and expansion of proteolytic, uremic toxin-generating bacteria. Bifidobacteria counts increased from 3.61 ± 0.54 to 4.90 ± 0.96 log CFU/g in the lactulose group (P <0.001), whereas the placebo group showed no meaningful change (Table 3, page 4). Lactobacilli similarly increased from 2.79 ± 1.00 to 3.87 ± 1.13 log CFU/g, also without improvement in the placebo arm. These taxa represent major microbial associations relevant to CKD because of their role in reducing luminal pH, suppressing pathogenic clostridia and Bacteroidaceae, and generating beneficial metabolites.

Renal function trends supported the microbiome findings. Serum creatinine significantly decreased in the lactulose group (3.90 ± 1.43 to 3.60 ± 1.44 mg/dL, P = 0.003) and significantly increased in the placebo group (3.87 ± 2.08 to 4.11 ± 1.99 mg/dL, P = 0.03). Although BUN did not differ significantly, the directionality suggested reduced nitrogenous waste retention. The analysis of percent change (page 3) revealed a statistically significant difference between groups, with creatinine decreasing in the lactulose arm and worsening in controls. The study did not measure specific uremic toxins such as p-cresol or indoxyl sulfate, but prior research cited within the article supports lactulose’s capacity to reduce toxin burden by modulating proteolytic fermentation.

Key implications

These findings provide evidence to clinicians that lactulose acts as a microbiome-targeted intervention in CKD, selectively expanding health-associated commensals and counteracting the dysbiosis that contributes to toxin generation. The increase in Bifidobacteria and Lactobacilli supports metabolic shifts toward saccharolytic rather than proteolytic fermentation, potentially reducing gut-derived uremic toxin formation. As CKD progression is tightly linked to intestinal dysbiosis and barrier dysfunction, restoring beneficial taxa may mitigate systemic inflammation and metabolic complications. The observed stabilization or improvement in creatinine further supports lactulose as an adjunctive therapy capable of modifying both microbial composition and renal biochemical markers. Given its affordability, safety profile, and bifidogenic potency, lactulose represents a feasible therapeutic candidate to integrate into microbiome-informed CKD management strategies.

Citation

Tayebi-Khosroshahi H, Habibzadeh A, Niknafs B, Ghotaslou R, Yeganeh Sefidan F, Ghojazadeh M, et al. The effect of lactulose supplementation on fecal microflora of patients with chronic kidney disease; a randomized clinical trial. J Renal Inj Prev. 2016;5(3):162-167. doi:10.15171/jrip.2016.34