For babies who are breastfed, their first source of sustenance is filled with proteins, sugars, hormones, vitamins, and minerals — just the right amount of nutrients for an infant.
That milk could also lower the risk of asthma, diabetes, and allergies. And it could make low-birth-weight, preterm babies up to 10 times less likely to develop necrotizing enterocolitis, a common intestinal disorder. Researchers who study human milk understand how the molecules affect everything from the gut microbiome to curbing chronic disease risk factors in babies.
Today, as scientists better understand how various components of human milk help improve the health of little ones, they are exploring ways to harness those benefits for people of all ages. One day, these molecules could become therapies for arthritis, atherosclerosis, Parkinson’s disease, and irritable bowel syndrome — and soon they could help build up the systems of people who are immunocompromised.
“It’s certainly an exciting field that holds a lot of potential for a wide variety of diseases,” said Katy Patras, an assistant professor at Baylor College of Medicine in Texas who has studied milk sugars and microbiota. But experts who study human milk say that there are a number of questions about how long lasting and how safe the new treatments may be, and about how they affect different diseases.
Researchers’ prime focus now is on complex sugars called human milk oligosaccharides (HMOs), the third most abundant component of human milk. They are not found in cow’s milk or infant formula, and their apparent benefit in supporting infant microbiomes hold promise, scientists believe, for adults.
Here’s what happens in infants: HMOs can’t be digested by babies, but the energy in the sugars help babies develop healthy guts. “I always say that mothers are prepared because they give you bacteria and then they pack a lunch for the bacteria, which are the HMOs,” said Grace Aldrovandi, a professor of pediatrics and chief of infectious diseases at the University of California, Los Angeles Mattel Children’s Hospital.
One of the first organisms that grows in a baby’s gut comes from the genus Bifidobacterium, and some of those bacteria have anti-inflammatory properties, according to David Mills, a microbiologist and professor at the University of California, Davis. As the bacteria consume the HMOs, they produce a bunch of short chain fatty acids that can modulate a baby’s immune system. Not only do they dampen inflammation, they also protect the colon, and lower the pH of the intestinal tract, acidifying it, so that bad bacteria don’t grow.
Prolacta Bioscience is one company that aims to take the research long conducted on how human milk helps infants and make it work for adults who may be immunocompromised or otherwise could benefit from microbiome repair. Based in California, Prolacta announced late last year that it provided an initial dose of a human-milk-based drug to the first patient participating in a randomized Phase 2a clinical trial. In this trial, researchers are evaluating the safety and efficacy of providing HMOs, in combination with the bacterium B. infantis, to adult patients with blood cancers who are undergoing stem cell transplantation.
Researchers want to know whether B. infantis, which helps to establish the microbiome in nursing infants, can help immunocompromised adults. “We want to take that biology and make it work in really fragile adult populations where we know that their damaged microbiomes play a role in their disease,” said Gregory McKenzie, microbiologist and vice president of product innovation at Prolacta.
The patients in this trial take the bacterial strain as a capsule and drink a small amount of the human milk sugars. Prolacta is currently testing two doses to see which one is more beneficial in repairing microbiomes.
Microbiome repair has in recent years gotten a boost from fecal transplants, especially those given to immunocompromised patients with C. difficile infections. “A lot of companies got into this space saying, ‘OK, I can give you this bacteria, I can give you my little special sauce cocktail of bacteria’ and there have been more failures than successes for reasons we don’t understand,” Aldrovandi explained. So there is hope that combining oligosaccharides with good bacterial strains will offer an alternative to fecal transplants by seeding an imbalanced microbiome to make it healthy. “What we’re doing is we’re putting those seeds down there, but then we’re feeding and watering them, so that we can improve the likelihood that they’ll grow and do the job that they’re meant to do,” McKenzie explained.
If B. infantis is successfully colonized in the gut, the resulting “garden” may help patients to be less dependent on antibiotics and less likely to have bad inflammatory outcomes.
Aldrovandi, who has served on Prolacta’s scientific advisory board, added that Prolacta’s clinical trial “is an interesting and good start,” but since it’s only looking at about 60 patients, the company will need to collect even more significant data in the future.
The hope, according to Prolacta’s McKenzie, is that the transplantation procedure becomes less risky, and hopefully will lead to a lower likelihood of death from infection. Patients in this trial are not being asked to completely stop taking antibiotics, so researchers are expecting to see fewer infections thanks to the Prolacta combined therapy. Eventually, that could lead to less antibiotic usage and fewer fevers, events of graft versus host disease, and bad inflammatory outcomes, McKenzie said.
McKenzie said Prolacta is focused on improving outcomes for cancer patients, because having that success will allow the company to move into other areas, such as infectious and inflammatory diseases in which the microbiome plays a role.
But the introduction of B. infantis into the adult gut, even if successful, may not be permanent — and it’s not clear whether that’s a good or bad thing. In 2008, Mills, the UC Davis professor, was an author on a study that sequenced the genome of B. infantis and that showed that as soon as babies start to be weaned and introduced to foods, which may include plant fibers, B. infantis is outcompeted by other bacteria. “So if you wanted to pick something to put in a cancer patient and then feel comfortable that it’s going away, this is a smart play,” said Mills. He added that other bifidobacteria and HMO combo could deliver the same benefits: increased production of short chain fatty acids to improve gut and bacterial function, but it’s not known whether they will remain in the gut when they are not being fed with HMOs. And, the more bifidobacteria there are in our gut, researchers believe it contributes to better health.
Another company, Seattle-based Intrinsic Medicine, is also developing HMO drugs by leveraging the supply of sugars originally synthesized for infant formula because it doesn’t have access to donor milk like Prolacta does. Since 2018, Intrinsic’s approach has been to better understand the individual components, since there are over 200 HMOs. Later this year, Phase 2 clinical trials for an HMO-derived drug for Parkinson’s will start in Australia, Intrinsic co-founder and chair Alex Martinez told STAT. After that, the company plans trials for Crohn’s disease and IBS. Intrinsic is also different from Prolacta because its approach is strictly prebiotic.
A prebiotic introduces an HMO to the gut with no microbes, while a probiotic would introduce live gut bacteria. The HMO that Intrinsic is using would feed and promote the diversity of existing native microbes, increasing the production of short chain fatty acids and other neuro-protective metabolites.
Martinez said that Intrinsic is evaluating individual sugars that it believes will have disease-modifying potential. Then after making comprehensive individual profiles through clinical trials, that will “open up a door to the combination therapies,” said Martinez.
As researchers explore various ways to use HMOs, another aspect to consider is safety. Some researchers consider using HMOs or a combination of HMOs and infant bacteria to be inherently safe, since in healthy infants there is a natural interplay between the two. Yet, that may be too sanguine a view. The FDA issued an advisory in 2023 on probiotic products used in hospitalized preterm infants, and associated the products with one infant death. It also cited more than two dozen adverse events in infants who were given probiotics. Infinant Health, which Mills co-founded and said he now has no official relationship with, was sent a warning letter from the FDA in late 2023 and as a result recalled its probiotic supplement Evivo for babies in the NICU, Mills told STAT. The use of similar therapies in combating necrotizing enterocolitis is widespread globally, however, and advocates have critiqued the FDA’s move.
In adults, some studies have shown that the use of probiotics for immunocompromised patients caused them to develop bacteremia — which suggests that care should be taken in adopting combined HMO-probiotic therapies. Patras, the Baylor College of Medicine professor, agreed and added that while a prebiotic might get around the problems that a probiotic might pose, there also is a risk when giving a prebiotic, because there might be bacteria lurking in our guts that aren’t currently causing disease, but could gain a foothold in the presence of HMOs. “We need more data, more science, to really ask all these questions,” Patras said.
Those questions include what HMOs do to different bacteria, or how different bacteria use HMOs and what those outcomes are. Once those questions are answered, researchers might be able to say whether a prebiotic is better than a probiotic.
In terms of the potential of human milk studies, research into HMO drug development is just the tip of the iceberg. Breast milk research has long focused on developing alternatives for those who have a low supply or for infants without access to breast milk. A company called Biomilq, for instance, synthesizes milk using mammary cells for people who have difficulty breastfeeding. And adults have occasionally tried to tap those benefits via dietary or nutritional supplements — and even by obtaining colostrum, the first milk produced by mammals within the first 48 to 72 hours after birth. Companies such as Armra are marketing colostrum, albeit from a bovine source, in powder form.
More than 50 clinical trials are going on around the world, with 14 in the U.S., trying to develop different interventions for adults using HMOs. Some researchers are exploring components other than sugars. Newton, Mass.-based Lactocore is looking at developing milk-derived therapies using proteins. At the Human Milk Institute, based out of the University of California, San Diego School of Medicine, researchers study the components of milk and assess the therapeutic potential of milk molecules. Some researchers dream big — the founding director, Lars Bode, also a professor of pediatrics at UC San Diego School of Medicine, envisions that one day there could be therapies for atherosclerosis and cardiovascular disease. In a preclinical mouse model, when UCSD researchers supplemented food with an HMO, they were able to reduce inflammation and the degree to which atherosclerotic lesions develop. These lesions can cause heart attacks and stroke.
Still, Bode warns that people need to be circumspect about chasing human milk as a wonder drug. “Human milk is for human babies, they need it the most. We’re talking about compounds that we can synthesize, that we can learn from human milk.”