Could the bacteria living in our digestive system influence how we feel emotionally?
Scientists have investigated this question for years, and a new clinical trial suggests certain probiotics may offer modest additional benefits alongside conventional depression treatment in older adults.
The study, published in the Journal of the American Geriatrics Society on June 17, 2026, examined whether daily probiotic supplementation could reduce symptoms of depression and anxiety in people aged 60 and older.
Researchers in India found that participants receiving probiotics alongside standard antidepressant care had lower overall depression and anxiety scores than those receiving a placebo. Both groups, however, improved substantially during the study.
The probiotic group also showed changes in a biological marker associated with brain function and increased levels of the supplemented bacteria in their gut.
These results are encouraging, but they come with important qualifications.
The trial included only 58 participants, experienced substantial dropout, and did not show a clear additional improvement in quality of life.
The findings suggest that probiotics deserve further investigation as a possible addition to standard depression care, not that they can replace antidepressants or psychotherapy.
Original study: Sinha et al., PRODG Clinical Trial, Journal of the American Geriatrics Society (2026).
Why Depression in Older Adults Needs More Attention
Depression is a serious mental health condition that can affect people at any age, including later life.
In older adults, symptoms may include persistent sadness, loss of interest in activities, changes in sleep or appetite, fatigue, difficulty concentrating, and feelings of hopelessness.
Depression may also occur alongside chronic pain, cardiovascular disease, reduced mobility, loneliness, bereavement, or other health challenges.
However, depression is not a normal or inevitable part of ageing.
The US National Institute on Ageing emphasises that older adults can benefit from established treatments, including psychotherapy, medication, or a combination of approaches.
Treating depression later in life can sometimes be complicated by multiple medical conditions, medication interactions, and differences in how older bodies process drugs.
Some patients do not respond adequately to their first treatment, while others experience adverse effects that make continued medication difficult.
These challenges have encouraged researchers to explore additional approaches that might support conventional care.
One area receiving increasing attention is the relationship between gut microorganisms and mental health.
Source: National Institute on Aging Depression and Older Adults.
What Is the Gut-Brain Axis?
The digestive system contains trillions of microorganisms, including bacteria, viruses, and fungi.
Collectively, these organisms and their genetic material form the gut microbiome.
Researchers have discovered that the gut and brain communicate through several interconnected pathways.
This communication network is commonly called the gut-brain axis.
It involves the nervous system, immune signalling, hormonal responses, and substances produced or modified by gut microorganisms.
For example, intestinal microbes can influence short-chain fatty acid production and tryptophan metabolism, an amino acid involved in serotonin-related pathways.
They may also interact with inflammation and the body’s stress response.
Scientists are investigating whether changes in these pathways can influence mood, anxiety, and other aspects of brain function.
However, the relationship is complex.
An association between certain gut bacteria and depression does not prove that the bacteria caused the condition.
Likewise, changing the gut microbiome does not automatically mean that depression will improve.
Human clinical trials are needed to determine whether modifying gut microorganisms produces meaningful mental health benefits.
What Are Probiotics?
Probiotics are live microorganisms that, when administered in adequate amounts, can provide a health benefit to the person consuming them.
They are found in certain supplements and fermented foods, although not every fermented food contains microorganisms that meet the scientific definition of a probiotic.
Different probiotic strains may produce different effects.
That distinction matters because evidence supporting one probiotic preparation doesn’t automatically apply to another product.
For example, two supplements may contain bacteria from the same species but use different strains, doses, and manufacturing methods.
Researchers have investigated probiotics for digestive conditions, immune responses, and, increasingly, mental health.
Probiotics being studied specifically for possible psychological effects are sometimes described as psychobiotics.
The term reflects an area of scientific research, not proof that such products are established treatments for psychiatric conditions.
For additional information, see the National Institutes of Health fact sheet on probiotics.
What Was the PRODG Clinical Trial?
The 2026 PRODG trial was designed to investigate whether adding probiotics to existing depression treatment could provide additional benefits for older adults.
PRODG stands for PRObiotics in Depression among Geriatrics.
The trial was conducted at two tertiary medical centres in India:
- All India Institute of Medical Sciences (AIIMS), New Delhi.
- National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru.
Researchers enrolled 58 adults aged 60 years or older who had been diagnosed with moderate unipolar depression.
Unipolar depression refers to depressive illness without the manic or hypomanic episodes characteristic of bipolar disorder.
Participants were randomly assigned to one of two groups.
Probiotic Group
Twenty-nine participants received a daily probiotic capsule alongside standard antidepressant treatment.
Placebo Group
Twenty-nine participants received a matching placebo capsule alongside standard antidepressant treatment.
Participants took the supplements for 12 weeks, followed by another 12 weeks of observation.
This created a total follow-up period of 24 weeks.
The researchers used a randomised, double-masked, placebo-controlled design.
This meant participants were randomly assigned to treatment groups, and neither participants nor relevant study personnel knew who received probiotics until the study’s blinding procedures were completed.
This design helps reduce some forms of bias, although it cannot eliminate all limitations.
Which Probiotic Bacteria Were Used?
The probiotic supplement contained two bacterial species:
1. Lactobacillus helveticus
This species is used in some fermented dairy products and probiotic preparations.
Researchers have studied certain strains for their possible effects on stress-related responses and emotional well-being.
2. Bifidobacterium longum
This species commonly occurs in the human intestinal microbiome.
Researchers have investigated certain strains for their effects on gut health, immune signalling, and psychological stress.
The supplement provided approximately 6 billion colony-forming units (CFU) daily, divided between the two bacterial species.
A colony-forming unit is a laboratory measure used to estimate the quantity of viable microorganisms in a preparation.
Participants were instructed to take one capsule after dinner.
These details describe the experimental intervention, not a medically established dosage for treating depression.
Importantly, the study does not demonstrate that every commercial supplement containing these species will produce the same results.
What Did the Researchers Measure?
The researchers evaluated several outcomes to understand whether probiotics might influence mental health or related biological processes.
The primary outcome was depression treatment response after 12 weeks.
A treatment response was defined as a reduction of at least 50% in scores on the Montgomery–Åsberg Depression Rating Scale (MADRS).
The MADRS is a clinical assessment tool that measures depressive symptom severity.
The team also examined:
- Anxiety symptoms using the Generalised Anxiety Disorder 7-item scale (GAD-7).
- Cognitive performance using the Montreal Cognitive Assessment (MoCA).
- Quality of life using the WHOQOL-BREF questionnaire.
- Blood levels of brain-derived neurotrophic factor (BDNF).
- Changes in selected gut microorganisms.
- Adverse events and treatment tolerability.
These measures allowed the researchers to examine psychological symptoms alongside selected biological changes.
Key Findings: Did Probiotics Improve Depression?
The trial produced several interesting results, but the findings require careful interpretation.
1. Depression Symptoms Improved in Both Groups
Participants receiving either probiotics or placebo showed substantial improvement in depression scores during follow-up.
The researchers’ statistical models also found that overall depression scores were lower in the probiotic group.
For the treatment-group comparison, the reported result was statistically significant (p = 0.001).
This suggests a possible additional benefit associated with probiotics.
However, the researchers did not find a statistically significant interaction between treatment group and time.
In simpler terms, although the probiotic group had lower overall symptom scores, the pattern of improvement over time was not clearly different between the two groups.
This limits how confidently we can interpret the results as evidence of a distinct probiotic treatment effect.
The study therefore supports a cautious conclusion: probiotics may offer modest additional symptom benefits, but the size and reliability of that benefit remain uncertain.
2. Anxiety Scores Were Also Lower in the Probiotic Group
The researchers observed a similar pattern for anxiety.
Both groups improved over time, but overall anxiety scores were lower among participants assigned to probiotics.
The between-group comparison was statistically significant (p = 0.002).
However, as with depression scores, the treatment-by-time interaction was not significant.
These findings suggest that probiotics could have additional effects on anxiety symptoms, but the results do not establish a consistent treatment advantage at every follow-up point.
Larger studies will be needed to determine whether the difference is clinically meaningful and reproducible.
3. Quality of Life Improved, but Not More With Probiotics
One of the trial’s important findings was that improvements in depression and anxiety scores did not translate into a clearly greater improvement in everyday quality of life.
Researchers assessed physical, psychological, social, and environmental aspects of quality of life.
All four domains improved significantly over time.
However, the probiotic group showed a clear additional benefit compared with standard treatment and placebo.
This distinction matters because successful depression treatment involves more than reducing symptom scores.
Meaningful recovery can include improved daily functioning, social relationships, independence, and overall well-being.
The study did not establish that probiotics produced superior outcomes in these broader areas.
4. Brain-Derived Neurotrophic Factor Increased
The researchers also investigated brain-derived neurotrophic factor (BDNF).
BDNF is a protein involved in neuronal survival, plasticity, and processes associated with learning and memory.
Neuroplasticity refers to the brain’s ability to adapt and modify connections between nerve cells.
Changes in BDNF signalling have been investigated in relation to depression and responses to treatment.
In the PRODG trial, the probiotic group showed a statistically significant increase in serum BDNF compared with placebo at 12 weeks (p = 0.04).
This result is biologically interesting because it suggests that probiotic supplementation may influence pathways associated with nervous system function.
However, measuring BDNF in blood does not directly establish that brain BDNF increased or that probiotics improved brain plasticity.
The study also cannot prove that BDNF changes caused the reported mood differences.
BDNF should therefore be considered an exploratory biological finding rather than evidence of brain repair.
5. The Supplemented Bacteria Increased in Stool Samples
Researchers examined stool samples from a small subset of participants to evaluate changes in the gut microbiome.
They reported that the relative abundance of the supplemented bacteria increased approximately eight- to tenfold during probiotic treatment.
This supports the conclusion that supplementation changed the measured intestinal microbial profile.
However, the microbiome analysis included only four participants per treatment group.
Such a small sample cannot establish a reliable relationship between bacterial changes and improvements in depression.
The study also did not prove that the supplemented microorganisms permanently colonised the intestine.
Further investigation is needed to determine whether these changes persist after treatment and whether they directly contribute to clinical outcomes.
Summary of the PRODG Trial Results
| Outcome | Main finding |
| Depression symptoms | Improved in both groups; lower overall scores with probiotics |
| Anxiety symptoms | Improved in both groups; lower overall scores with probiotics |
| Improvement over time | No significant treatment-by-time interaction for depression or anxiety |
| Quality of life | Improved in both groups without clear additional probiotic benefit |
| Serum BDNF | Increased in the probiotic group at 12 weeks |
| Supplemented gut bacteria | Higher measured abundance in a small probiotic subgroup |
| Tolerability | Mostly mild gastrointestinal complaints reported |
| Overall conclusion | Preliminary evidence of possible modest adjunctive benefits |
Source: Read the full PRODG study.
Were the Probiotics Safe?
The researchers reported that the probiotic intervention was generally well tolerated during the trial.
No serious psychiatric adverse events were reported.
However, seven participants in the probiotic group experienced mild gastrointestinal symptoms during the first six weeks.
These included bloating, abdominal fullness, and constipation.
The small study population and short treatment period limit conclusions about uncommon or long-term adverse effects.
Probiotics are often well tolerated by generally healthy adults, but they are not completely risk-free.
According to the US National Centre for Complementary and Integrative Health, people with severe illnesses or weakened immune systems may face greater risks from live microorganism supplements.
Although serious infections linked to probiotics are uncommon, medically vulnerable populations have reported them.
This is particularly relevant to older adults who may have multiple medical conditions or use immune-suppressing treatments.
Anyone considering probiotics alongside prescribed depression medication should discuss the decision with a qualified healthcare professional.
Source: NCCIH Probiotics: Usefulness and Safety.
Why the Study’s Limitations Matter
The results are promising enough to justify further investigation, but they are not strong enough to establish probiotics as a standard treatment for late-life depression.
Several limitations are particularly important.
1. Only 58 Participants Were Enrolled
The original enrollment target was 80 participants, but researchers recruited 58.
This is a small sample for evaluating a treatment effect, especially when depressive symptoms and treatment responses can vary substantially between individuals.
2. More Than Half the Participants Were Lost to Follow-Up
By 24 weeks, 29 of the 58 participants had been lost to follow-up.
That represents 50% of the randomised participants.
The high dropout rate creates substantial uncertainty about the results, particularly because participants who remain in a study may differ from those who leave.
The researchers also could not perform a conventional intention-to-treat analysis with imputation because of the amount of missing data.
3. Participants Received Different Standard Treatments
All participants received usual antidepressant care, but treatment was managed according to clinical needs.
Some also received medications for anxiety or sleep-related symptoms.
Differences in antidepressant doses and benzodiazepine use influenced selected study outcomes.
This makes it harder to isolate the probiotics’ effects.
4. The Trial Did Not Demonstrate Clear Improvement in Quality of Life
Although depression and anxiety scores improved, probiotics did not produce a clear additional quality-of-life benefit.
This raises questions about the functional significance of the observed symptom differences.
5. Biological Changes Do Not Prove the Proposed Mechanism
The increase in serum BDNF and the measured bacterial changes are interesting.
However, they do not show that changing gut bacteria improved brain function or mood.
6. The Results May Not Apply to All Older Adults
The study excluded people with several important conditions, including significant cognitive impairment, certain neurological disorders, severe psychiatric risks, uncontrolled illnesses, and immunosuppressive treatment.
As a result, the findings cannot automatically be generalised to older adults with these conditions.
October 2026 Update: Researchers Question the Statistical Interpretation
An important development followed the original PRODG study’s publication.
On October 21, 2026, a letter titled PRODG Multi-Center Trial: A Critical Appraisal of Efficacy Estimates and Statistical Interpretation appeared in the Journal of the American Geriatrics Society.
Tingting Sun and Yin Wang authored the commentary.
Its publication highlights ongoing scientific scrutiny of how to interpret the trial’s efficacy estimates and statistical findings.
The distinction between an overall treatment-group difference and a statistically significant treatment-by-time interaction is especially important when evaluating the original results.
The publicly available citation confirms that this critical appraisal was published, but you should review its full argument before attributing specific additional criticisms to the authors.
The PRODG trial should therefore be understood as exploratory research that requires independent replication.
Reference: PRODG Multi-Center Trial: A Critical Appraisal of Efficacy Estimates and Statistical Interpretation.
Could Probiotics Become Part of Depression Treatment?
The trial contributes to an emerging area of research examining whether targeted changes to the gut microbiome can support mental health care.
Scientists remain interested for several reasons.
First, certain gut microorganisms may influence immune activity and metabolism.
Second, microbial products can interact with pathways involved in stress regulation and communication between the gut and nervous system.
Third, probiotics may be more accessible than some more intensive treatments, although their affordability and suitability vary by location and product.
However, these possibilities do not establish that taking probiotics is an effective treatment for clinical depression.
A larger clinical trial would need to confirm that a defined probiotic preparation produces meaningful benefits beyond placebo.
It would also need to assess remission, quality of life, daily functioning, safety, and longer-term outcomes.
Researchers would ideally use standardised background depression treatment and limit missing follow-up data.
Until such evidence is available, probiotics should be considered an experimental adjunct rather than a replacement for established care.
What Should Older Adults With Depression Do Now?
For older adults experiencing depressive symptoms, the strongest available clinical evidence continues to support established treatments.
Depending on a person’s needs and medical history, these may include:
- Psychotherapy, such as cognitive behavioural therapy or interpersonal therapy.
- Antidepressant medications prescribed and monitored by a healthcare professional.
- A combination of medication and psychotherapy.
- Assessment and treatment of other medical conditions contributing to symptoms.
- Additional specialist treatments when depression does not respond adequately to initial care.
The American Psychological Association recommends evidence-based psychotherapies and certain antidepressant medications for older adults with depression.
People who are interested in probiotic supplementation should first discuss potential benefits, risks, and product selection with their treating clinician.
No one should stop prescribed antidepressants, reduce their dose, or replace psychotherapy with probiotic supplements based on this trial.
Source: American Psychological Association Depression Treatments for Older Adults.
Conclusion: Promising Research, but Not Yet a Proven Treatment
The 2026 PRODG trial adds an intriguing contribution to research on the gut microbiome-mental health relationship.
Researchers found modest overall improvements in depression and anxiety measures among older adults who received probiotics alongside standard treatment.
The intervention also produced measurable changes in serum BDNF and selected intestinal microorganisms.
However, the trial’s small size, substantial participant dropout, variable background treatment, and lack of additional quality-of-life benefits limit the strength of its conclusions.
The October 2026 critical appraisal reinforces the importance of careful statistical interpretation and independent confirmation.
For now, the most appropriate conclusion is that probiotics may have potential as an additional intervention for late-life depression, but their clinical effectiveness remains uncertain.
Further research may help determine whether specific bacterial strains can provide reliable benefits for particular patients.
Until then, evidence-based mental health treatment remains the foundation of depression care.
References
1. Original PRODG Clinical Trial (2026)
Sinha, P., Chatterjee, P., Kathiresan, P., et al. Efficacy of Adjunct Probiotics as Compared to the Standard Care in Moderate Unipolar Depression Among Geriatric Patients: A Randomized Double-Blind Placebo-Controlled Pilot Multi-Center Trial (PRODG). Journal of the American Geriatrics Society, 74(7), 2021–2031.
https://doi.org/10.1111/jgs.70530
2. Full Open-Access Research Paper
PubMed Central, US National Library of Medicine.
https://pmc.ncbi.nlm.nih.gov/articles/PMC13418558
3. October 2026 Critical Appraisal
Sun, T., & Wang, Y. PRODG Multi-Center Trial: A Critical Appraisal of Efficacy Estimates and Statistical Interpretation.
https://doi.org/10.1111/jgs.70806
4. National Institute on Aging
Depression and Older Adults.
https://www.nia.nih.gov/depression
5. American Psychological Association
Depression Treatments for Older Adults.
https://www.apa.org/depression-guideline/older-adults
6. National Institutes of Health Office of Dietary Supplements
Probiotics: Health Professional Fact Sheet.
https://ods.od.nih.gov/factsheets/Probiotics-HealthProfessional
7. National Center for Complementary and Integrative Health
Probiotics: Usefulness and Safety.
https://www.nccih.nih.gov/health/probiotics-usefulness-and-safety
8. Wiley Research News (June 17, 2026)
Can Probiotics Help Treat Depression?