Mapping the pathway to gut health in HIV and SIV infections

November 19, 2019

A UC Davis study found that the damaged gut lining (known as leaky gut) in monkeys infected with chronic simian immunodeficiency virus (SIV), an HIV-like virus, was rapidly repaired within five hours of receiving Lactobacillus plantarum bacteria.

The study, published today in the PNAS, linked chronically inflamed leaky gut to the loss of PPARα signaling (a nuclear receptor protein responsible for regulating cell metabolism) and subsequent damage to mitochondria - the cell's power house.

The researchers found that L. plantarum activated PPARα signaling and revived mitochondrial flow, repairing the gut barrier in only five hours of exposure.

The outcome lends hope that leaky gut, a common condition among HIV patients, could be effectively treated in the future.

HIV and the damage to the gut lining


The gut, home to majority of the lymphoid tissue in the body, is an early target of HIV. The virus severely damages the immune and epithelial cells in the gut's lining. This damage leads to an inflamed and leaky gut with weakened defense system and decreased nutrient absorption.

Anti-retroviral therapy (ART) for HIV has been successful in limiting the damage to the body's immune system. Yet, it has failed to consistently or completely repair the damage to the gut and its lining.

"We wanted to map the pathways that lead to sustained damage in the gut and to identify ways to intervene and support its repair," said Katti Crakes, doctoral student in the schools of Medicine and Veterinary Medicine at UC Davis and first author on the study.

The researchers found that HIV attacks the gut's epithelial cells by targeting and draining the mitochondria.

"To reverse the damage caused by HIV and to increase the efficacy of ART, it is important to restore mitochondrial function and to rapidly repair the gut epithelium and immune defense," said Satya Dandekar, professor of microbiology and immunology at UC Davis School of Medicine and senior author.

Identifying cell signaling regulators for restoring the gut barrier
The bacteria present in the gut are known to play an important role in supporting and repairing the gut functioning. The study specifically tested the impact of L. plantarum bacteria on gut epithelial barrier of SIV infected rhesus macaques.

"We challenged the capacity of L. plantarum bacteria and their metabolites to restore the gut functions in an extremely inflamed visibly disrupted gut environment," Dandekar said.

The researchers found that L. plantarum were able to survive and remain metabolically active in inflamed gut. The bacteria repaired the gut barrier by targeting and restoring the mitochondria in the intestinal epithelial cells damaged by SIV as well as HIV. These findings provide translational insights into restoring gut immunity and function, both of which are essential for successful HIV cure efforts.
-end-
In addition to Crakes and Dandekar, UC Davis researchers on this paper were Clarissa Santos Rocha, Irina Grishina, Lauren Hirao, Christopher Gaulke, Anne Fenton, Juan Arredondo and Sumathi Sankaran-Walters from the Department of Medical Microbiology and Immunology; Eleonora Napoli, Sandipan Datta, Gino Cortopassi and Cecilia Giulivi from the Department of Molecular Biosciences in the School of Veterinary Medicine; and Maria Marco from the Department of Food Science and Technology.

This study was supported by the National Institutes of Health grant AI123105 and P51OD011107. Katti Crakes received the NIH pre-doctoral training grants OD010956, OD010931-12 and GM131457.

University of California - Davis Health

Related HIV Articles from Brightsurf:

BEAT-HIV Delaney collaboratory issues recommendations measuring persistent HIV reservoirs
Spearheaded by Wistar scientists, top worldwide HIV researchers from the BEAT-HIV Martin Delaney Collaboratory to Cure HIV-1 Infection by Combination Immunotherapy (BEAT-HIV Collaboratory) compiled the first comprehensive set of recommendations on how to best measure the size of persistent HIV reservoirs during cure-directed clinical studies.

The Lancet HIV: Study suggests a second patient has been cured of HIV
A study of the second HIV patient to undergo successful stem cell transplantation from donors with a HIV-resistant gene, finds that there was no active viral infection in the patient's blood 30 months after they stopped anti-retroviral therapy, according to a case report published in The Lancet HIV journal and presented at CROI (Conference on Retroviruses and Opportunistic Infections).

Children with HIV score below HIV-negative peers in cognitive, motor function tests
Children who acquired HIV in utero or during birth or breastfeeding did not perform as well as their peers who do not have HIV on tests measuring cognitive ability, motor function and attention, according to a report published online today in Clinical Infectious Diseases.

Efforts to end the HIV epidemic must not ignore people already living with HIV
Efforts to prevent new HIV transmissions in the US must be accompanied by addressing HIV-associated comorbidities to improve the health of people already living with HIV, NIH experts assert in the third of a series of JAMA commentaries.

The Lancet HIV: Severe anti-LGBT legislations associated with lower testing and awareness of HIV in African countries
This first systematic review to investigate HIV testing, treatment and viral suppression in men who have sex with men in Africa finds that among the most recent studies (conducted after 2011) only half of men have been tested for HIV in the past 12 months.

The Lancet HIV: Tenfold increase in number of adolescents on HIV treatment in South Africa since 2010, but many still untreated
A new study of more than 700,000 one to 19-year olds being treated for HIV infection suggests a ten-fold increase in the number of adolescents aged 15 to 19 receiving HIV treatment in South Africa, according to results published in The Lancet HIV journal.

Starting HIV treatment in ERs may be key to ending HIV spread worldwide
In a follow-up study conducted in South Africa, Johns Hopkins Medicine researchers say they have evidence that hospital emergency departments (EDs) worldwide may be key strategic settings for curbing the spread of HIV infections in hard-to-reach populations if the EDs jump-start treatment and case management as well as diagnosis of the disease.

NIH HIV experts prioritize research to achieve sustained ART-free HIV remission
Achieving sustained remission of HIV without life-long antiretroviral therapy (ART) is a top HIV research priority, according to a new commentary in JAMA by experts at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

The Lancet HIV: PrEP implementation is associated with a rapid decline in new HIV infections
Study from Australia is the first to evaluate a population-level roll-out of pre-exposure prophylaxis (PrEP) in men who have sex with men.

Researchers date 'hibernating' HIV strains, advancing BC's leadership in HIV cure research
Researchers have developed a novel way for dating 'hibernating' HIV strains, in an advancement for HIV cure research.

Read More: HIV News and HIV Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.