Underweight Adults Gained 5x More Weight When Probiotics Were Added to Their Diet

Gaining weight when severely underweight sounds straightforward: eat more. But for the estimated hundreds of millions of people living with undernutrition globally, simply increasing caloric intake often fails to translate into meaningful body mass gains, partly because a disrupted gut microbiome impairs nutrient absorption and appetite regulation. A new double-blind, randomized controlled trial published in BMC Nutrition by Hatami A and colleagues tested whether adding a three-strain probiotic supplement to a structured weight gain diet could change that equation for severely underweight adults. The preliminary results suggest it can, and by a larger margin than most researchers expected.

Probiotic Combination Produced 2.41 kg Weight Gain Versus 0.44 kg on Diet Alone

Over eight weeks, the 95 participants who received the probiotic combination, containing Lacticaseibacillus rhamnosus GG, Lactobacillus acidophilus, and Lacticaseibacillus casei at 10^9 colony-forming units per capsule, gained an average of 2.41 kg of body weight. The placebo group, following the same additional 500 kcal/day dietary intervention, gained just 0.44 kg. That gap, confirmed at p < 0.001, was not a rounding difference; the probiotic group gained roughly 5.5 times more weight over the same period.

BMI followed the same pattern. The probiotic group saw their BMI climb by 0.83 kg/m² on average, compared with 0.24 kg/m² in the placebo group, again a statistically significant difference. Body fat percentage increased by 3.23 percentage points in the probiotic arm versus 1.03 in the placebo arm. Fat mass itself rose by 1.90 kg in the probiotic group and 0.89 kg in the placebo group. As published findings from this trial cohort confirm, the probiotic supplement combined with a weight-gain diet significantly enhanced anthropometric measures across the board.

None of these participants started in a healthy weight range. All had a BMI below 18.5 kg/m² at enrollment, meeting the clinical threshold for underweight, and were aged 18 to 60, recruited in Mashhad, Iran.

Appetite Signals Shifted, Not Just Calorie Totals

The weight difference was not purely mechanical. The probiotic group did not just eat the mandated extra 500 kcal; they spontaneously consumed an additional 263.55 kcal per day on average, compared with just 30.75 kcal per day more in the placebo group (p < 0.001). Something was changing the drive to eat.

Visual analog scale scores confirmed this. Participants in the probiotic arm reported significantly greater hunger and desire to eat, alongside reduced feelings of satiety and fullness before meals, all at p < 0.001. Gut-brain signaling along the microbiota-gut-brain axis is a plausible mechanism: certain probiotic strains modulate peptide hormones like ghrelin and peptide YY, which regulate appetite directly. The study did not measure these hormones directly, but the behavioral signal is consistent with that pathway.

Bowel function also shifted. Stool consistency in the probiotic group moved by approximately one unit on the Bristol Stool Scale toward softer, more regular stools (p = 0.01), which is consistent with improved gut transit and, potentially, better nutrient absorption conditions.

How a Double-Blind RCT Design Strengthens the Signal

The study used a double-blind, placebo-controlled design, recognized as the gold standard for nutrition clinical trials because it controls for expectation effects from both participants and researchers. Both capsule groups followed an identical-looking protocol; only the contents differed. Primary endpoints were pre-registered with the Iranian Registry of Clinical Trials (IRCT20230310057667N1), and ethics approval came from Mashhad University of Medical Sciences.

Secondary endpoints were unusually broad for a nutrition trial of this size. Researchers measured gut permeability via serum zonulin concentration, a marker for how leaky the intestinal barrier has become. Oxidative stress was tracked through four separate biomarkers: serum malondialdehyde, total antioxidant capacity, total oxidant status, and glutathione peroxidase activity. Inflammation was assessed via C-reactive protein and erythrocyte sedimentation rate. This biomarker panel was designed to probe whether probiotic-driven microbiome changes were doing anything beyond shifting the scale, including reducing the chronic low-grade inflammation often seen in malnourished patients.

Open Questions About Mechanism, Duration, and Lean Mass

The trial's eight-week window captures a meaningful metabolic shift, but it is too short to answer whether these gains persist, whether lean mass eventually catches up to fat mass gains, or whether the appetite changes represent a durable recalibration or a temporary perturbation.

The body composition data also deserve scrutiny. The larger gains in body fat percentage relative to BMI and fat mass suggest the intervention favored adipose tissue more than muscle. For people recovering from severe undernutrition, some fat gain is appropriate and expected, but clinicians managing underweight patients ultimately want lean mass recovery too. The study did not report muscle mass separately.

Broader limitations in probiotic research apply here as well: this is a single trial from one geographic population, the three-strain combination makes it impossible to attribute effects to any individual bacterium, and the 10^9 CFU dose may not be optimal for all underweight presentations. Gut microbiome composition at baseline, which was not reported in the protocol data available, could also modulate response substantially.

What Comes Next for Probiotic-Assisted Weight Gain Protocols

If the full trial data, including the zonulin, oxidative stress, and inflammatory biomarker results, support the body composition findings, this protocol could become a practical adjunct to clinical nutrition programs for underweight patients. The combination of a defined caloric surplus with a standardized multi-strain probiotic is straightforward enough for outpatient implementation.

The authors plan to disseminate results through peer-reviewed journals and conference presentations. Meanwhile, the broader field is moving toward next-generation probiotic formulations engineered with greater strain specificity and stability, which could eventually replace the current generation of broadly-acting supplements with therapies tuned to specific metabolic deficits.

For now, this trial adds meaningful weight, literal and evidential, to the case that gut microbiota manipulation is not just a digestive health story. In severely underweight adults, the difference between 0.44 kg and 2.41 kg gained over eight weeks is clinically significant. Whether that signal holds across larger, more diverse populations is the question the field needs to answer next.

Evidence rating

INVESTIGATIONAL — 76/100

Caveats:

• This is a study protocol — no trial results have been published yet. All reported findings are projections or preliminary observations, not confirmed outcomes.
• The article describes the methodology of a planned or ongoing trial; any effect estimates should not be interpreted as established evidence.

This article is a published protocol for a double-blind RCT, not a results report; no trial outcomes have yet been reported. The planned study will enroll approximately 100 underweight adults and is registered with the Iranian Registry of Clinical Trials. Evidence from this work cannot be assessed until results are published.

References

1. Alireza Hatami, Maryam Ahmadi-Khorram, Asma Afshari, et al. (2026). The effects of a novel combination of a probiotic supplement (L. rhamnosus GG, L. acidophilus, and L. casei) with a weight gain intervention on body composition, appetite, gut permeability, oxidative stress, and inflammation in underweight adults: study protocol for a double-blind, randomized controlled trial. BMC Nutrition. https://doi.org/10.1186/s40795-026-01403-3
2. Alireza Hatami, Maryam Ahmadi-Khorram, Reza Rahmanian, et al. (2025). Effects of a Novel Probiotic Supplement with Weight Gain Intervention on Anthropometry, Body Composition, and Appetite in Underweight Adults: A Randomized Controlled Trial. Journal of Dietary Supplements. https://doi.org/10.1080/19390211.2025.2561132
3. Delyse SY Tien, Meghan Hockey, Daniel So, et al. (2024). Recommendations for Designing, Conducting, and Reporting Feeding Trials in Nutrition Research. Advances in Nutrition. https://doi.org/10.1016/j.advnut.2024.100283
4. Richard LJ Day, Ashton J Harper, Rachel M Woods, Owen G Davies, Liam M Heaney (2019). Probiotics: Current Landscape and Future Horizons. Future Science OA. https://doi.org/10.4155/fsoa-2019-0004
5. Ashutosh Tiwari, Dyah Ika Krisnawati, Erna Susilowati, Chinmaya Mutalik, Tsung-Rong Kuo (2024). Next-Generation Probiotics and Chronic Diseases: A Review of Current Research and Future Directions. Journal of Agricultural and Food Chemistry. https://doi.org/10.1021/acs.jafc.4c08702