Written by Alexa Heathorn, MS, CNS, Science Writer. Eight weeks of supplementation with a multi-strain probiotic combined with an energy-surplus diet significantly improved serum zonulin, reduced markers of oxidative stress and systemic inflammation, and enhanced biomarkers of gut barrier function in undernourished adults compared with diet alone.

According to the World Health Organization, undernutrition, defined as insufficient energy and nutrient intake, affects approximately 390 million adults worldwide.¹ Undernutrition is associated with disruption of the gut microbiome, impaired intestinal barrier function, systemic inflammation, and oxidative stress.¹ An imbalance in the gut microbiota can alter tight junction proteins, including zonulin and occludin, increasing intestinal permeability and allowing toxins to enter the bloodstream and promote inflammation.¹

One strategy to support gut health is probiotic supplementation. Probiotics are beneficial microorganisms that produce short-chain fatty acids, support intestinal barrier integrity, reduce inflammation and oxidative stress, and enhance antioxidant activity.¹ Among the most widely studied are Lactobacillus species, including Lactobacillus acidophilus, which supports gut barrier integrity; Lactobacillus casei, which supports mucosal immunity and reduces inflammation; and Lactobacillus rhamnosus, which has been associated with weight gain in undernourished populations.¹ Despite encouraging findings, studies evaluating probiotics and gut barrier function have produced mixed results, and most research has focused on overweight individuals or those with chronic disease.¹ Consequently, the effects of multi-strain probiotics in underweight adults, particularly when combined with a weight-gain dietary intervention, remain underexplored.¹

This 8-week, double-blind, randomized, placebo-controlled trial investigated the effects of a multi-strain probiotic supplement containing Lactobacillus acidophilus, Lactobacillus casei, and Lactobacillus rhamnosus, combined with a weight-gain dietary intervention, on gut barrier function, inflammation, and oxidative stress in underweight adults.¹ The primary outcome was serum zonulin, a marker of intestinal permeability.¹ Secondary outcomes included markers of oxidative stress (total antioxidant capacity, glutathione peroxidase, malondialdehyde, and total oxidant status) and inflammation (C-reactive protein and erythrocyte sedimentation rate).¹

The study included 95 adults aged 18–60 years with undernutrition, defined as a BMI below 18.5 kg/m².¹ Participants were randomly assigned to receive either two probiotic capsules or identical placebo capsules daily while following a diet providing a 500 kcal/day energy surplus.¹

The results were as follows:

Gut Barrier Function
Serum zonulin, a marker of intestinal permeability, decreased significantly more in the probiotic group than in the placebo group (−0.98 ± 1.61 vs. −0.22 ± 1.12 ng/mL; p = 0.047), suggesting improved gut barrier integrity.¹

Oxidative Stress
Compared with placebo, probiotic supplementation significantly increased total antioxidant capacity (+0.40 vs. −0.01 mmol/L) and glutathione peroxidase (+4.0 vs. −0.8 nmol/mL), while reducing total oxidant status (−4.22 vs. +0.79 μmol/L) and malondialdehyde (−0.046 vs. +0.006 nmol/mL) (all p < 0.001).¹

Inflammation
Systemic inflammation also improved in the probiotic group. C-reactive protein (CRP) decreased by 0.50 mg/L compared with an increase of 0.10 mg/L in the placebo group, while erythrocyte sedimentation rate (ESR) decreased by 1 mm/h compared with an increase of 1 mm/h in the placebo group (both p < 0.001).¹

Several limitations should be considered when interpreting these findings. All participants followed a 500 kcal/day energy-surplus diet, making it difficult to distinguish how much of the observed improvements were due to the probiotic supplementation versus the increased calorie intake.¹ The study also included only underweight adults and lasted just 8 weeks, limiting the generalizability of the findings to healthy or overweight populations and preventing conclusions about long-term benefits.¹ Additionally, the researchers measured laboratory markers of gut health, oxidative stress, and inflammation rather than clinical outcomes. Future studies evaluating digestive symptoms, quality of life, and other patient-centered outcomes would provide a more complete understanding of the intervention’s clinical impact. Finally, because only one probiotic formulation was evaluated, the findings cannot be generalized to other probiotic strains or dosages.¹

Despite these limitations, this study provides promising evidence that a targeted multi-strain probiotic combined with an energy-surplus diet can improve markers of gut barrier integrity, oxidative stress, and systemic inflammation in undernourished adults.¹ While additional research is needed to determine whether these biomarker improvements translate into better digestive health, quality of life, and long-term clinical outcomes, these findings support the potential role of targeted probiotic supplementation as a safe and effective adjunct to nutritional therapy for undernutrition.¹

Click here to read the full text study.

Posted July 7, 2026.

Alexa Heathorn, MS, CNS-c, is a clinical nutritionist specializing in metabolic health, hormonal balance, and gastrointestinal restoration through root-cause functional nutrition. She earned her master’s degree in Nutrition from Bastyr University and is currently a Certified Nutrition Specialist (CNS) candidate. Alexa also works as a research writer and functional health consultant, translating complex science into actionable strategies for practitioners and wellness companies. Learn more at www.bloomedwellness.com.

References:

1. Ahmadi-Khorram M, Hatami A, Eskandari MH, et al. A Novel Combination of Probiotic Supplements Reduces Gut Permeability, Oxidative Stress, and Inflammation in Undernourished Adults: A Randomized Controlled Trial. Food Sci Nutr. 2026;14(6):e71915. Published 2026 May 27. doi:10.1002/fsn3.71915