Probiotic + Prebiotic for Fatty Liver in HIV/AIDS

(GLAM HIV NAFLD Trial)

Overseen By Curtis L Gabriel, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Vanderbilt University Medical Center

Must be taking: Antiretrovirals

Must not be taking: Corticosteroids, Tamoxifen, Methotrexate, others

Disqualifiers: Pregnancy, Celiac, Hepatitis C, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

63 Participants Needed

Trial Summary

What is the purpose of this trial?

Persons with human immunodeficiency virus (HIV) have higher risk of developing fatty liver disease (NAFLD) than HIV-negative persons but the reasons for this discrepancy are not known. Changes in the intestinal microbiome may contribute to the development of NAFLD in persons with HIV (PWH) through impairment of barrier function of the intestinal wall and by producing metabolites that are harmful to the liver. This project will test the hypothesis that HIV-related NAFLD is associated with differences in the intestinal microbiome and that supplementation with probiotic and prebiotic fiber will lead to improvements in markers of NAFLD in PWH.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those on certain medications like systemic corticosteroids, tamoxifen, and methotrexate. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Probiotic + Prebiotic for Fatty Liver in HIV/AIDS?

Research shows that probiotics and prebiotics can improve liver health by reducing liver enzymes and cholesterol levels in people with nonalcoholic fatty liver disease (NAFLD). This suggests they might also help manage fatty liver in individuals with HIV/AIDS. ^{1 2 3 4 5}

Is the combination of probiotics and prebiotics safe for humans, including those with HIV/AIDS?

Research suggests that prebiotics and probiotics are generally safe for humans, including those with HIV/AIDS. Studies have shown that they can help improve gut health and immune function without significant safety concerns. ^{6 7 8 9 10}

How does the probiotic and prebiotic treatment for fatty liver in HIV/AIDS differ from other treatments?

This treatment is unique because it combines probiotics (beneficial bacteria) and prebiotics (food for these bacteria) to improve gut health, which may help reduce inflammation and oxidative stress (damage caused by free radicals) associated with fatty liver disease. Unlike traditional treatments that may focus on medication or lifestyle changes, this approach targets the gut microbiota (community of microorganisms in the intestines) to potentially improve liver health. ^{3 11 12 13 14}

Eligibility Criteria

This trial is for adults with HIV who have high triglycerides, signs of metabolic syndrome, or a diagnosis of fatty liver disease. They must be on stable antiretroviral therapy with controlled HIV and not pregnant, planning pregnancy, or have other liver diseases. Participants need to speak English and have access to a private fridge.

Inclusion Criteria

Persistently abnormal transaminases: elevated liver enzymes defined by transaminases ≥1.5 upper limit of normal ([ULN] = 35 IU/mL) and/or gammaglutamyltransferase level ≥2 ULN (ULN = 60 IU/L) on 2 blood samples within at least a 3-month interval

BMI ≥ 30 kg/m2

Documented HIV infection

Exclusion Criteria

I have been diagnosed with celiac disease.

I have been diagnosed with a liver disease other than NAFLD.

I have had cirrhosis or a liver transplant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a probiotic containing multiple strains of bacteria supporting butyrate synthesis and prebiotic fiber

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Prebiotic
• Probiotic

Trial Overview The study investigates if probiotics and prebiotics can improve markers of fatty liver disease in people with HIV by altering the gut microbiome. It's testing whether these supplements can help maintain a healthy gut-liver relationship.

Participant Groups

Group I: Probiotic and Prebiotic Fiber Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Findings from Research

In a study involving 72 patients with nonalcoholic fatty liver disease (NAFLD), consuming probiotic yogurt for 8 weeks led to significant reductions in liver enzymes and cholesterol levels, indicating potential benefits for managing NAFLD.

Specifically, the probiotic yogurt reduced alanine aminotransferase and aspartate aminotransferase levels by approximately 4.67% and 5.42%, respectively, and lowered total cholesterol and LDL cholesterol by 4.1% and 6.92%, suggesting it may help improve metabolic factors associated with NAFLD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of probiotic yogurt consumption on metabolic factors in individuals with nonalcoholic fatty liver disease. Nabavi, S., Rafraf, M., Somi, MH., et al.[2022]

A systematic review of 105 studies involving 6826 subjects found that oral intake of probiotics led to significant improvements in metabolic risk factors for overweight individuals, including reductions in body weight, body mass index, waist circumference, body fat mass, and visceral fat.

In type 2 diabetics, probiotics were effective in lowering fasting glucose, glycated hemoglobin, insulin levels, and insulin resistance, indicating their potential role in managing diabetes and related metabolic conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of bacterial probiotics on obesity, diabetes and non-alcoholic fatty liver disease related variables: a systematic review and meta-analysis of randomised controlled trials. Koutnikova, H., Genser, B., Monteiro-Sepulveda, M., et al.[2020]

Supplementation with prebiotics or symbiotics may lead to changes in the intestinal microbiota of patients with non-alcoholic fatty liver disease (NAFLD), based on a systematic review of four studies.

Despite these changes in gut microbiota, the current evidence does not support the clinical use of these supplements as a treatment for NAFLD due to high risk of bias in the studies reviewed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PROBIOTIC, PREBIOTIC OR SYMBIOTIC SUPPLEMENTATION IMPACTS ON INTESTINAL MICROBIOTA IN PATIENTS WITH NONALCOHOLIC FATTY LIVER DISEASE: A SYSTEMATIC REVIEW. Souza, CA., Rocha, R., Costa, PRF., et al.[2022]

In a clinical trial with 50 NASH patients, synbiotic supplementation combined with nutritional counseling led to significant reductions in liver fat (steatosis), weight loss, and decreased body measurements compared to nutritional counseling alone.

While the synbiotic treatment did not improve intestinal permeability or levels of lipopolysaccharides, it was effective in reducing steatosis, highlighting its potential as a beneficial intervention for managing NASH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beneficial Effect of Synbiotic Supplementation on Hepatic Steatosis and Anthropometric Parameters, But Not on Gut Permeability in a Population with Nonalcoholic Steatohepatitis. Ferolla, SM., Couto, CA., Costa-Silva, L., et al.[2022]

Probiotic supplementation significantly reduced liver enzymes (ALT, AST, GGT) and triglyceride levels in patients with nonalcoholic fatty liver disease (NAFLD) compared to a control group, indicating its potential efficacy in improving liver health.

Prebiotic supplementation also showed beneficial effects on liver enzymes and lipid profiles, suggesting that both probiotics and prebiotics may help manage metabolic parameters in NAFLD patients, although no significant differences were found between the groups after the intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of probiotic and prebiotic supplementation on metabolic parameters, liver aminotransferases, and systemic inflammation in nonalcoholic fatty liver disease: A randomized clinical trial. Behrouz, V., Aryaeian, N., Zahedi, MJ., et al.[2020]

In a study involving 30 obese women over 3 months, treatment with inulin-type fructans (ITF prebiotics) significantly altered gut microbiota composition, increasing beneficial bacteria like Bifidobacterium and Faecalibacterium prausnitzii, which are linked to lower serum lipopolysaccharide levels.

The ITF prebiotics also resulted in a slight decrease in fat mass and changes in plasma metabolites, suggesting that these prebiotics can modestly influence host metabolism and may have implications for obesity and diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insight into the prebiotic concept: lessons from an exploratory, double blind intervention study with inulin-type fructans in obese women. Dewulf, EM., Cani, PD., Claus, SP., et al.[2022]

A 6-week prebiotic supplementation significantly improved the gut microbiota in HIV-infected individuals, especially in viremic untreated patients, by increasing the diversity and abundance of active bacteria with beneficial properties.

The prebiotics not only reduced dysbiosis but also enhanced the presence of immunomodulatory bacteria, such as Bifidobacteriaceae, to levels comparable to healthy individuals, indicating a potential therapeutic strategy for managing gut health in HIV patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of HIV, antiretroviral therapy and prebiotics on the active fraction of the gut microbiota. Deusch, S., Serrano-Villar, S., Rojo, D., et al.[2019]

In a study using fecal cultures from healthy and morbidly obese adults, different prebiotics were tested, revealing that 1-kestose had the most significant impact on gut microbiota composition and metabolic activity.

Prebiotic modulation led to increased Bacteroides and Faecalibacterium in obese individuals, while normal-weight individuals showed higher levels of Bifidobacterium and Faecalibacterium, highlighting the need for tailored prebiotic treatments based on individual microbiota profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vitro Evaluation of Different Prebiotics on the Modulation of Gut Microbiota Composition and Function in Morbid Obese and Normal-Weight Subjects. Nogacka, AM., Salazar, N., Arboleya, S., et al.[2023]

In a pilot study involving 44 participants, including untreated HIV+ patients and those on antiretroviral therapy, a 6-week prebiotic intervention significantly improved gut microbiota composition, particularly in untreated HIV+ individuals, reducing HIV-associated dysbiosis.

The intervention led to declines in markers of bacterial translocation and T-cell activation, along with increased butyrate production, suggesting that targeting the bacterial butyrate synthesis pathway could be a promising strategy for improving immune function in HIV patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of prebiotics on microbial dysbiosis, butyrate production and immunity in HIV-infected subjects. Serrano-Villar, S., Vázquez-Castellanos, JF., Vallejo, A., et al.[2023]

In a 3-year observational study involving 68 participants consuming probiotic yogurt and 82 control participants, yogurt consumption was linked to a significant increase in CD4 count, with an average increase of 0.28 cells/μL/day after starting the yogurt (P=0.003).

The study suggests that probiotic yogurt can enhance immune function in people living with HIV/AIDS, as the increase in CD4 count remained significant even after adjusting for antiretroviral medication use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probiotic yogurt consumption is associated with an increase of CD4 count among people living with HIV/AIDS. Irvine, SL., Hummelen, R., Hekmat, S., et al.[2022]

The prebiotic oligofructose (OFS) significantly reduced energy intake, weight gain, and fat mass in obese rats, indicating its strong impact on body composition compared to the probiotic Bifidobacterium animalis subsp. lactis BB-12.

Both OFS and BB-12 improved glycemic control, with OFS increasing GLP-1 levels and BB-12 enhancing GLP-2 levels, highlighting the beneficial effects of both prebiotics and probiotics on metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined effects of oligofructose and Bifidobacterium animalis on gut microbiota and glycemia in obese rats. Bomhof, MR., Saha, DC., Reid, DT., et al.[2014]

In a study involving 75 patients with non-alcoholic fatty liver disease (NAFLD), supplementation with probiotics and/or prebiotics significantly reduced body weight, body mass index, waist and hip circumferences, and inflammatory markers like tumor necrosis factor-α compared to a placebo.

The combination of probiotics and prebiotics was particularly effective in lowering high-sensitive C-reactive protein (hs-CRP), indicating enhanced anti-inflammatory effects, while no significant differences were found between the individual and combined treatments for other oxidative stress markers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pro- and prebiotic effects on oxidative stress and inflammatory markers in non-alcoholic fatty liver disease. Javadi, L., Khoshbaten, M., Safaiyan, A., et al.[2019]

A meta-analysis of 28 clinical trials involving 1555 patients with nonalcoholic fatty liver disease (NAFLD) showed that probiotic therapy significantly improved several health markers, including body mass index and liver enzymes, over treatment periods of 4 to 28 weeks.

Probiotics were found to be more effective than placebo in managing NAFLD, suggesting they could serve as a valuable complementary treatment option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review with Meta-Analysis: The Effects of Probiotics in Nonalcoholic Fatty Liver Disease. Xiao, MW., Lin, SX., Shen, ZH., et al.[2022]

In a double-blind, placebo-controlled trial involving 58 type 2 diabetes patients with nonalcoholic fatty liver disease (NAFLD), the probiotic 'Symbiter' significantly reduced the fatty liver index (FLI) from 84.33 to 78.73, indicating a decrease in liver fat (p<0.001).

The probiotic treatment also led to significant reductions in serum aminotransferase levels (AST and GGT) and inflammatory markers TNF-α and IL-6, suggesting that modulating gut microbiota could be a promising new therapy for NAFLD, warranting further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Multi-strain Probiotic Reduces the Fatty Liver Index, Cytokines and Aminotransferase levels in NAFLD Patients: Evidence from a Randomized Clinical Trial. Kobyliak, N., Abenavoli, L., Mykhalchyshyn, G., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Effects of probiotic yogurt consumption on metabolic factors in individuals with nonalcoholic fatty liver disease. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Impact of bacterial probiotics on obesity, diabetes and non-alcoholic fatty liver disease related variables: a systematic review and meta-analysis of randomised controlled trials. [2020]

3. Brazil pubmed.ncbi.nlm.nih.gov

PROBIOTIC, PREBIOTIC OR SYMBIOTIC SUPPLEMENTATION IMPACTS ON INTESTINAL MICROBIOTA IN PATIENTS WITH NONALCOHOLIC FATTY LIVER DISEASE: A SYSTEMATIC REVIEW. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Beneficial Effect of Synbiotic Supplementation on Hepatic Steatosis and Anthropometric Parameters, But Not on Gut Permeability in a Population with Nonalcoholic Steatohepatitis. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Effects of probiotic and prebiotic supplementation on metabolic parameters, liver aminotransferases, and systemic inflammation in nonalcoholic fatty liver disease: A randomized clinical trial. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Insight into the prebiotic concept: lessons from an exploratory, double blind intervention study with inulin-type fructans in obese women. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Effects of HIV, antiretroviral therapy and prebiotics on the active fraction of the gut microbiota. [2019]

8. Switzerland pubmed.ncbi.nlm.nih.gov

In Vitro Evaluation of Different Prebiotics on the Modulation of Gut Microbiota Composition and Function in Morbid Obese and Normal-Weight Subjects. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

The effects of prebiotics on microbial dysbiosis, butyrate production and immunity in HIV-infected subjects. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Probiotic yogurt consumption is associated with an increase of CD4 count among people living with HIV/AIDS. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Combined effects of oligofructose and Bifidobacterium animalis on gut microbiota and glycemia in obese rats. [2014]

12. China pubmed.ncbi.nlm.nih.gov

Pro- and prebiotic effects on oxidative stress and inflammatory markers in non-alcoholic fatty liver disease. [2019]

13. Egypt pubmed.ncbi.nlm.nih.gov

Systematic Review with Meta-Analysis: The Effects of Probiotics in Nonalcoholic Fatty Liver Disease. [2022]

14. Romania pubmed.ncbi.nlm.nih.gov

A Multi-strain Probiotic Reduces the Fatty Liver Index, Cytokines and Aminotransferase levels in NAFLD Patients: Evidence from a Randomized Clinical Trial. [2019]