Are Probiotics the Next Wonder Drug in HIV Care?

Slideshow

• 

  Slide

  Photo Credit: Dr Gopal Murti/Science Source.

• 

  Effect on Diarrhea

  Diarrhea is a common problem in HIV-infected persons. The virus and the use of antiretroviral therapy have been associated with chronic (≥4 weeks) and occasional diarrhea. In these patients, diarrhea is associated with significant morbidity, decreased quality of life, and an increased risk for mortality in those with advanced disease.¹ Therefore, prevention and effective treatment of diarrhea are essential, and some studies have suggested probiotics may be the solution.²

  A systematic review found level B evidence for use of probiotics to treat diarrhea, but not enough data were available to make recommendations regarding their use in HIV-infected patients.² Two studies assessing the fungal species Saccharomyces boulardii in patients with advanced AIDS reported significant benefits, indicating this species may be particularly promising; however, further studies are needed to determine which doses and species alone or in combination may provide the most benefit.² Photo Credit: Scimat /Science Source

• 

  Effect on CD4 Counts

  HIV has been found to attack the gut and gut-associated lymphoid tissue, which is the largest immune compartment in the body, harboring more than 60% of the body's immune cells, including CD4 cells.^3,4 This has led researchers to investigate whether probiotics might improve or help maintain CD4 cell counts in people living with HIV.⁵

  In a 2016 systematic review of 13 studies that assessed the effect of probiotics on CD4 counts, 7 studies reported benefit and 6 reported insignificant benefits or negative CD4 outcomes.⁵ On the basis of these findings, the authors concluded "consumption of probiotics over a prolonged period of time may improve CD4 counts in people living with HIV."⁵ Another systematic review, which included 15 studies, reached a similar conclusion, with the authors noting, "our analysis suggests a potential role for the use of probiotics in improving CD4 counts modestly.”²

• 

  Preventing HIV-Associated Bacterial Translocation

  Bacterial translocation is "the passage of viable bacteria from the [gastrointestinal] tract to extraintestinal sites, such as the mesenteric lymph node complex, liver, spleen, kidneys, and bloodstream."⁶ In HIV-infected persons, it can occur when the virus breaches the gut's mucosal integrity, enabling gut microbiome organisms to migrate to other organ systems, resulting in infections. Animal studies have suggested probiotics may prevent bacterial translocation by improving intestinal barrier function.⁷

  A 2016 systematic review provided further evidence of this, with 4 of 6 studies showing probiotics to have some beneficial effects on bacterial translocation markers, such as increases in CD4 counts and reductions in interleukin 6 and lipopolysaccharide binding protein.² The authors concluded that although "the data are inconclusive, there is a signal that prebiotics may have a modest impact on markers of translocation and/or markers of inflammation and immune activation.”²

• 

  Delaying Disease Progression

  Gut microbiota dysbiosis has been associated with HIV disease progression. One study found abundant Proteobacteria and depleted Bacteroidia in HIV+ patients, which was associated with mucosal immune disruption, T-cell activation, and chronic inflammation, including in those receiving highly active antiretroviral therapy.⁸ The level of dysbiosis correlated with tryptophan catabolism and plasma concentrations of interleukin 6. On the basis of these findings, the authors concluded "gut-resident microbial populations may influence intestinal homeostasis during HIV disease."⁸

  Probiotics have been reported to facilitate intestinal epithelial homeostasis via numerous biological mechanisms, such as by preventing cytokine and chemical-induced epithelial apoptosis and disruption of barrier function.⁹ Studies examining whether maintaining epithelial homeostasis via probiotics can protect against HIV are ongoing.

• 

  Protecting Against Inflammation

  Although modern antiretroviral therapy has significantly enhanced the care and life expectancies of HIV+ patients, they continue to be at higher risk for adverse health conditions, such as cardiovascular, neurodegenerative, and gastrointestinal diseases resulting from HIV-associated inflammation. A 2016 study by investigators in Rome suggests a high concentration of probiotic could reduce inflammation in these patients.¹⁰

  The study investigators measured the inflammatory markers neopterin in cerebrospinal fluid and expression of indolamine-2,3-dioxygenase mRNA in gut-associated lymphoid tissue in HIV-1-infected patients receiving effective combined antiretroviral therapy at baseline and 6 months after adding a probiotic regimen using a high-potency formulation containing 8 bacterial strains. They found a significant reduction of both markers after probiotic supplementation.¹⁰ Other studies investigating the probiotic combination are ongoing and are recruiting patients (ClinicalTrials.gov: NCT02441231; NCT02441244).

• 

  Most Common Adverse Effects

  Because probiotics are ingested as living organisms, there is potential for toxicity and even infections.¹³ But probiotics are generally well tolerated across patient populations, with few to no adverse effects and benefits that far outweigh any risks.

  When adverse effects occur, they are typically gastrointestinal-related, with gas and bloating being the most common. A systematic review found that patients with HIV or AIDS are no more vulnerable to experiencing these effects than noninfected persons.² However, a variety of factors can affect probiotics' overall safety and tolerability, including vulnerability of the user (eg, age, presence of underlying medical conditions), dose and duration of consumption, and method and frequency of administration, all of which should be considered by clinicians before recommending probiotics to individual patients.¹⁴

• 

  Risk for Systemic Infections

  There is some evidence that probiotics might increase the risk for systemic infections, including bacteremia and fungemia, in a variety of patient populations, including immunocompromised individuals.¹⁵ In 2016, bacteremia in a patient with AIDS was reported that was attributed to excess consumption of a Lactobacillus acidophilus-enriched yogurt.¹⁶ Although Lactobacillus species have been increasingly associated with invasive infection among immunocompromised individuals,¹⁵ other organisms have also been implicated, including S boulardii, Bacillus subtilis, and Bifidobacterium breve.¹⁵

  A systematic review that sought to better elucidate the risk for systemic infections from probiotic consumption in persons with HIV or AIDS found the risk to be exceedingly low, regardless of species, with an estimated number needed to harm of 7369.² There were no reports of any probiotic-associated bacteremia or fungemia in the study sample (N=5060).²

• 

  Role in Developing Countries

  The role of probiotics in preventing HIV, slowing disease progression, and treating HIV- or antiretroviral-associated symptoms has yet to be definitively defined. However, their use may be particularly beneficial in developing counties, where HIV is most prevalent and access to nutrition and HIV treatments are scarce or individuals may be resistant to receiving Western treatments.

  A study investigating Lactobacillus rhamnosus GR-1-enriched yogurt in HIV+ individuals in Sub-Saharan Africa found it to be safely consumed, with many showing benefits in gut health, nutritional status, and immune status, with an average increase in CD4 counts of 0.16 cells/μL daily.¹⁷ The probiotic yogurt was produced in a local, community-run kitchen, enabling it to be readily available and easily accessible. In another study, hospitalized HIV+ children in Malawi who had severe acute malnutrition and received a probiotic had reduced outpatient mortality, indicating further studies are warranted.¹⁸

• 

  Effect on Bacterial Vaginosis

  Bacterial vaginosis (BV) increases women's susceptibility to acquiring HIV and might result in higher HIV levels and easier disease transmission, particularly to male partners.^2,11 A systematic review found 1 study assessing the effect of a probiotic in HIV+ women with BV, and none of the participants was cured after 6 months of treatment.² However, researchers from Harvard reported promising results using an engineered form of Lactobacillus jensenii, an organism prevalent in healthy vaginal microbiomes, to express the HIV-1 entry inhibitor modified cyanovirin-N, enabling it to act as a live vaginal anti-HIV microbicide.¹²

  Some evidence suggests probiotics, particularly Lactobacilli, might protect against BV, and even against HIV, via multiple mechanisms, such as by producing bacteriocins, lowering pH of the genital tract, and/or releasing hydrogen peroxide.¹³ Further high-quality studies are needed to determine the role of probiotics in BV. Photo Credit: CDC/M Rein.