Microbiome-based treatments not ready for prime time

Manipulating the microbiome has been shown to impact conditions including acne, atopic dermatitis (AD), autoimmune diseases and melanoma.

Dr. Greiling

“Hopefully,” says Teri Greiling, M.D., Ph.D. “research in these areas will provide us with therapeutic options in the future, but we’re not there yet.” She is assistant professor of dermatology and associate program director of dermatology research at Oregon Health & Science University, Portland.

Acne

Dermatologists target Cutibacterium acnes with antimicrobials because this entity has the most evidence showing that it plays a key role in acne, she says.

“However, it’s unclear whether a single culprit strain of C. acnes causes acne, or if a patient’s individual immune response to C. acnes is to blame,” she says.

Emerging strategies to target C. acnes involve colonization with probiotic “good” bacteria, and killing C. acnes specifically while sparing beneficial bacteria.

Autoimmune conditions

“There’s been some emerging evidence that interactions between specific bacterial species and the immune system can trigger and sustain autoimmunity in multiple different autoimmune diseases,” she explains.

For example, certain skin and gut bacteria may initiate lupus in genetically susceptible individuals.

“The immune system is attacking the bacteria, but those bacteria have conserved proteins that cross-react with human cells, turning a healthy immune response into autoimmunity,” she says.

In ulcerative colitis, the first clinical trials of fecal transplants have shown the ability to allow patients to achieve remission without immunosuppressive therapy.

Atopic dermatitis

“We know that flares of atopic dermatitis are associated with overgrowth of Staphylococcus aureus and loss of most other healthy microbes on the skin,” she says.

In early clinical trials, topical replacement of Roseomonas mucosa reduced AD flares, she says.

“Interestingly, without treating the bacteria itself, just treating the immune response with steroids or dupilumab can also restore the healthy microbiota. It’s counterintuitive that immune suppression allows restoration of the normal healthy microbiota,” she says.

Melanoma

Well-done studies have shown that when using PD-1 inhibitors or CTLA4 inhibitors for metastatic melanoma, investigators can predict who will survive based on the balance of patients’ gut bacteria, Dr. Greiling says. But because three recent publications highlight helpful or harmful impacts of different bacteria, she adds, the key players remain unclear.

“However, a meta-analysis has shown that if you’re treated with antibiotics within six weeks before starting immune therapy, you have a much poorer likelihood of responding to immune therapy,¹” she says.

Regarding probiotics in general, Dr. Greiling says that the dozen or so FDA-approved strains earned approval due to their safety.

“But these strains are probably not that useful in terms of most of these diseases. There are finally clinical trials in progress of microbiota-based therapies, but the safety and efficacy in big trials aren’t proven,” she says.

DISCLOSURE:

Dr. Greiling reports no relevant financial interests.

REFERENCE:

1 Wilson BE, Routy B, Nagrial A, Chin VT. The effect of antibiotics on clinical outcomes in immune-checkpoint blockade: a systematic review and meta-analysis of observational studies. Cancer Immunol Immunother. 2020;69(3):343-354.