Researchers look to augment the bugs’ natural abundance to limit the likelihood at-risk babies will become infected
No one argues that when it comes to feeding baby, mom’s milk is best. But mothers infected with HIV, the AIDS virus, face a dilemma: Because some of their virus can be shed in breast milk, babies risk becoming infected as they drink it. Two research teams are now investigating a germ-warfare strategy to treat such vulnerable infants.
They would supplement breast milk with HIV-quashing bacteria. These beneficial microbes can’t guarantee a child won’t become infected, but they could greatly diminish the chance this will happen, says HIV specialist Ruth Connor of Dartmouth Medical School in Lebanon, N.H.
In the August Breastfeeding Medicine, she and colleagues from Complutense University of Madrid, in Spain, report isolating certain lactic acid bacteria from the breast milk of healthy women that substantially inhibit the growth and infectivity of human immunodeficiency virus type 1, or HIV-1.
In test-tube studies, all 38 strains of bacteria tested — representing 15 different species — showed some inhibition of HIV. The least potent bugs inhibited the virus’ infectivity by 6.7 percent; the best shut down 55.5 percent of HIV’s ability to infect cells.
The researchers tested killed bacteria and cell-free goop that had been produced by those bacteria. “We wanted to distinguish whether any ability to inhibit HIV was due to specific components of the bacteria, such as their outer cell wall, or just the soluble constituents that bacteria make,” Connor explains. In the end, each proved antiviral, she notes, although the bacterial carcasses performed best.
All heat-killed carcasses exhibited some inhibition of HIV infectivity, and 11 cut HIV’s infectivity by 41 percent or more. By contrast, soluble cell compounds produced by just six of the strains proved inhibitory, and only one reduced infectivity by at least 41 percent.
Connor says her team’s finding helps explain something she and other virologists have puzzled over: why many infants who breastfeed from HIV-positive women fail to acquire mom’s infection.
Still unknown, she says, is whether one or more of the top performing bacteria (such as Lactobacillus curvatus / gramininis VM25; L. fermentum VMA and Pediococcus pentosaceus VM95) offer substantial protection on their own against HIV or work collaboratively as a natural bacterial cocktail. But the ultimate goal, Connor says, would be to create a probiotic supplement to augment breast milk by delivering a bonus quantity of such microbes. Probiotics are beneficial bacteria sold as dietary supplements to aid in digestion or to augment health.
Some probiotics aimed at infants already exist, Connor notes. They’re administered as oral drops or added to infant formula. The idea is to seed an infant’s gut with living communities of the beneficial bugs so that they’re ready to clobber any HIV that might be ingested. It’s “an extra layer of protection against infection,” Connor says.
Toward that end, such probiotics would work best if administered as soon as breastfeeding commences — at birth — so that a baby’s largely microbefree gut could be preferentially colonized with anti-HIV strains.
Still, such an infant supplement is a long way off. It must undergo testing to see that when administered at high doses these bacteria won’t cause diarrhea or some other undesirable side effect — initially in adults, later in healthy infants and eventually in babies at high risk of HIV infection.
“Lactic acid bacteria, the general type of microbes they isolated from breast milk, can be isolated from lots of places,” including plants, wine and fermenting vegetables or dairy products, notes David Mills of the University of California, Davis. He says this naturally leads one to ask: “Does that non-human isolated strain of the same species cause the same effect? If it does, that would suggest this is a very nonspecific interaction (but still perhaps very helpful).”
“I was surprised that so many organisms have been found in breast milk, as it is still not clear how they get there,” says Gregor Reid of the Canadian Research and Development Centre for Probiotics at the University of Western Ontario in London. One theory as to their source, he says, is that late in pregnancy, dendritic cells — certain white blood cells active in immunity — “in the gut pick up the lactobacilli or other organisms and 'deposit' them in the mammary ducts.” If confirmed, he says, it should be possible to deliver probiotic lactobacilli to the ducts, and to choose the lactobacilli that best inhibit HIV binding.”
But it is that apparent lack of specificity among breast-milk bacteria in targeting HIV that raises a red flag for Lin Tao. This microbiologist at the University of Illinois at Chicago’s Department of Oral Biology has spent the better part of a decade working on a probiotic treatment for infants whose mothers are infected with HIV. He said his team screened thousands of candidate bacteria from the guts of healthy infants before they identified a strain that effectively binds and kills HIV.
Tao says that because all 38 bacterial strains investigated in the new paper showed some efficacy against HIV, he suspects that most weren’t truly antiviral so much as able — at least in the huge quantities administered in the test-tube — to perturb HIV’s environment, making it generally inhospitable to the virus. He questions whether the bugs Connor’s team is looking at would perform nearly as well when encountered in — or as a supplement to — breast milk.
Moreover, he doubts the value of one or more probiotic bacteria that even in high concentrations only inhibit 30 to 50 percent of the virus. The strain his group is studying does far better but still falls short of wiping out all HIV that might enter an infant’s gut.
That’s why his group’s new strategy is to include a second probiotic, one that can bolster an infant’s immune system.
The first bacterium reduces the number of virus particles that survive in the infant gut. The second bug, by enhancing immunity, increases the threshold number of viruses needed to cause infection, Tao says.
This probiotic one-two punch is currently undergoing tests in animals. But progress is slow, he notes, “because we have a very difficult time raising venture capital.” This dietary guard against HIV would be targeted at helping poor infants and women in Africa, he explains, where antiviral drug therapy — the U.S. gold standard — is beyond the economic reach of most infected individuals. It’s “because they cannot become millionaires producing things to save infants [in the developing world],” Tao says, that “venture capitalists have rated our product’s value at zero.”
Martin, V., . . . and R.I Connor. Inhibition of Human Immunodeficiency Virus Type 1 by Lactic Acid Bacteria from Human Breastmilk. Breastfeeding Medicine. Vol. 5, August 2010, p. 153. doi:10.1089/bfm.2010.0001.
Reid, G., et al. Potential Uses of Probiotics in Clinical Practice. Clinical Microbiology Reviews. Vol. 16, October 2003, p. 658. doi:10.1128.CMR.16.4.658-672.2003.