Prebiotics for AUD and HIV/AIDS

Overseen By Lena DiBenedetto, B.S

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Rush University Medical Center

Must be taking: Antiretrovirals

Must not be taking: Anticoagulants, Immunosuppressives, NSAIDs, others

Disqualifiers: Substance abuse, Obesity, Diabetes, others

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

Compensation: Varies

Number of Visits: 2

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must be able to temporarily stop using antiplatelet or anticoagulant medications for endoscopy. If you are on these medications, discuss with the trial team to see if you can safely pause them.

What data supports the effectiveness of the treatment Prebiotic, Oligofructose-enriched inulin (OEI), Prebiotin for AUD and HIV/AIDS?

Research shows that prebiotics, like inulin-type fructans, can improve gut health by increasing beneficial bacteria and reducing harmful ones. In HIV-infected individuals, prebiotics have been found to improve gut microbiota composition and reduce inflammation, which may help manage symptoms related to HIV/AIDS. ^{1 2 3 4 5}

Is the prebiotic treatment safe for humans?

Research on inulin-type fructans (a type of prebiotic) suggests they are generally safe for humans, with studies showing benefits like improved gut health and increased absorption of minerals. However, individual responses can vary, and more research is needed to fully understand their effects. ^{2 3 6 7 8}

How does the prebiotic treatment for AUD and HIV/AIDS differ from other treatments?

This treatment is unique because it uses prebiotics, specifically inulin-type fructans, to improve gut health by promoting beneficial bacteria. Unlike traditional treatments that may focus on medication, this approach aims to enhance the gut microbiota, which can have positive effects on overall health and metabolism. ^{2 3 7 9 10}

What is the purpose of this trial?

Alcohol use disorder (AUD) has been associated with high prevalence of inflammation-associated co-morbidities in people living with HIV even those receiving effective antiretroviral therapy (ART). Our preliminary data support a model in which the combined insult of AUD and HIV on the gut, specifically on the microbiota and intestinal barrier integrity, exacerbates inflammation. Our preliminary data using intestinal organoids also suggest a potential mechanism for AUD-mediated changes in the gut barrier function during HIV; the intestines of HIV+ individuals have low resilience to alcohol induced intestinal barrier disruption caused by high levels of oxidative stress. Finally, our preliminary data also suggest a potential approach to enhance the integrity of the intestinal barrier and reduce gut derived inflammation in people living with HIV with/without AUD- short chain fatty acid prebiotics. These prebiotics prevent alcohol mediated adverse effects on the intestinal barrier and inflammation by preventing oxidative stress. These prebiotics are safe and decrease gut inflammation in humans. 20 HIV+ ART+ (10 AUD- and 10 AUD +), will be recruited for a prebiotic intervention. This is a proof-of-concept observational study to establish a causal link between microbiota-gut and HIV pathology during ART by asking whether modifying microbiota and gut milieu impacts intestinal barrier function, systemic inflammation, and brain pathology in HIV+ people. Participants will have two study visits, where stool collection and blood draw will be collected, as well as questionnaires. These participants are part of the larger observation study (n=160), which will test the hypothesis that intestines from HIV+ individuals have lower resilience to alcohol mediated gut barrier disruption than intestines from HIV-negative controls. We will recruit the following groups of participants: HIV+ ART+ AUD-; HIV+ ART+ AUD+; HIV- AUD- ; HIV- AUD+. Blood, urine, stool, and intestinal biopsies will be collected from participants to compare intestinal barrier integrity, system and gut inflammation, immune activation, oxidative stress, microbiome/metabolome. and HIV reservois. Second, lleal/colonic organoids from HIV- and HIV ART+ individuals will be generated to examine their resilience to alcohol-induced intestinal barrier disruption.

Eligibility Criteria

This trial is for people aged 45-70 with HIV on ART therapy for at least a year, with stable treatment and undetectable viral load for six months. It's also open to HIV-negative individuals matching the same age, lifestyle, and health criteria. Excluded are those with certain medical conditions or risks related to endoscopy, substance abuse issues, recent vaccines or infections, immunosuppressive treatments, alcoholism including binging behavior.

Inclusion Criteria

HIV+ Group: Ability and willingness to provide informed consent

I am HIV positive, confirmed by tests.

I have been on HIV treatment for at least a year.

Exclusion Criteria

I have had surgery on my digestive system.

I am unable to sign a consent form.

Any condition that, in the opinion of the gastrointestinal (GI) specialist, would either be a contraindication to endoscopy or would increase the risk from sedation, endoscopy, or mucosal biopsies

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Prebiotic Intervention

Participants receive a commercially available prebiotic (FOS) for 10 days

10 days

2 visits (in-person)

Follow-up

Participants are monitored for changes in plasma and stool SCFA levels, stool and intestinal microbiota composition, and intestinal permeability

4 weeks

Treatment Details

Interventions

• Prebiotic

Trial Overview The study tests if prebiotics can improve gut health and reduce inflammation in people living with HIV who may also have an alcohol use disorder (AUD). Participants will consume prebiotics for ten days and provide stool samples and blood draws during two visits. The larger study includes both HIV-positive/negative groups with/without AUD to compare intestinal resilience against alcohol-induced damage.

Participant Groups

Group I: HIV-infected ART-suppressed individuals with no AUD Experimental Treatment 1 Intervention

Only 10 HIV+ ART+,AUD - individuals will be invited to take part in a prebiotic sub study, which they will take a commercially available prebiotic (FOS) for 10 days

Group II: HIV-infected ART-suppressed individuals with AUD Experimental Treatment 1 Intervention

Only 10 HIV+ ART+,AUD + individuals will be invited to take part in a prebiotic sub study, which they will take a commercially available prebiotic (FOS) for 10 days

Who Is Running the Clinical Trial?

Rush University Medical Center

Lead Sponsor

Trials

448

Recruited

247,000+

Findings from Research

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 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]

Inulin-type fructans (ITF) have been shown to positively influence the intestinal microbiota by increasing beneficial bacteria such as Bifidobacterium and Lactobacillus, which can lead to improved gut health and function.

ITF intake is associated with several health benefits, including better intestinal barrier function, improved insulin sensitivity, lower triglycerides, enhanced mineral absorption, and increased feelings of fullness, although more research is needed to understand how chain length affects these outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Prebiotic Potential of Inulin-Type Fructans: A Systematic Review. Hughes, RL., Alvarado, DA., Swanson, KS., 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 pilot study involving 57 HIV-1-infected adults, a prebiotic oligosaccharide mixture significantly improved gut microbiota composition, increasing beneficial bifidobacteria and reducing harmful bacteria over 12 weeks.

The treatment also led to a reduction in activated CD4(+) T cells and soluble CD14 levels, along with enhanced natural killer (NK) cell activity, suggesting potential immune system benefits for HAART-naive individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Specific prebiotics modulate gut microbiota and immune activation in HAART-naive HIV-infected adults: results of the "COPA" pilot randomized trial. Gori, A., Rizzardini, G., Van't Land, B., et al.[2023]

Infants consuming formula with prebiotics (galacto-oligosaccharides and fructo-oligosaccharides) showed a significantly higher abundance and proportion of beneficial bifidobacteria compared to those without prebiotics, indicating a positive effect on gut microbiota composition.

The prebiotic-containing formula was well tolerated and resulted in lower fecal pH, but did not affect stool patterns, tolerance, or growth compared to the control group, suggesting it is a safe option for infant nutrition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of prebiotic-containing infant formula on gastrointestinal tolerance and fecal microbiota in a randomized controlled trial. Holscher, HD., Faust, KL., Czerkies, LA., et al.[2020]

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 study of 66 adult men with functional constipation, a synbiotic preparation significantly increased stool frequency and improved stool consistency after 4 weeks of treatment compared to a placebo.

No adverse effects were reported in the synbiotic group, suggesting it is a safe option for treating functional constipation, but further research is needed to confirm its efficacy in broader populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synbiotic preparation in men suffering from functional constipation: a randomised controlled trial. Fateh, R., Iravani, S., Frootan, M., et al.[2022]

In a study involving conventional rats, a 2-week intervention with a probiotic mixture supplemented with galacto-oligosaccharide (GOS) significantly increased the previously undetectable levels of bifidobacteria, while lactic acid bacteria levels remained unchanged due to already high baseline numbers.

In healthy human subjects, the probiotic mixture with polydextrose (PDX) led to a notable increase in bifidobacteria and lactic acid bacteria counts, suggesting that the effectiveness of pro- and prebiotics depends on the initial levels of these bacteria, and highlighting the importance of tailored combinations for optimal results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of prebiotic supplementation on a probiotic bacteria mixture: comparison between a rat model and clinical trials. Tiihonen, K., Suomalainen, T., Tynkkynen, S., et al.[2016]

Native chicory inulin enhances the production of beneficial short-chain fatty acids, particularly propionic and butyric acid, in the human gut, indicating its prebiotic potential.

Real-time PCR is more effective than traditional culture methods for detecting increases in bifidobacteria populations along the colon, showing that inulin has a significant prebiotic effect from the proximal to distal colon.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prebiotic effects of chicory inulin in the simulator of the human intestinal microbial ecosystem. de Wiele, TV., Boon, N., Possemiers, S., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

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

2. 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]

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

The Prebiotic Potential of Inulin-Type Fructans: A Systematic Review. [2023]

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

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

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

Specific prebiotics modulate gut microbiota and immune activation in HAART-naive HIV-infected adults: results of the "COPA" pilot randomized trial. [2023]

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

Effects of prebiotic-containing infant formula on gastrointestinal tolerance and fecal microbiota in a randomized controlled trial. [2020]

7. 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]

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

Synbiotic preparation in men suffering from functional constipation: a randomised controlled trial. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Effect of prebiotic supplementation on a probiotic bacteria mixture: comparison between a rat model and clinical trials. [2016]

10. England pubmed.ncbi.nlm.nih.gov

Prebiotic effects of chicory inulin in the simulator of the human intestinal microbial ecosystem. [2023]