Microbiome-modulating therapies, including prebiotics, probiotics, and postbiotics, are safe and associated with “clinically meaningful” lesion reductions in patients with acne, according to a recently published systematic review.

Among these therapies, “probiotics currently have the strongest evidence base, while prebiotics and postbiotics are promising adjuncts,” the authors from the Department of Dermatology and Cutaneous Surgery, University of Miami, Miami, wrote in the review, published online in Dermatology and Therapy.

“Larger, standardized randomized trials are needed to clarify comparative efficacy, optimal formulations, and durability,” they added.

Gut-Skin Axis and the Microbiome

The pathogenesis of acne arises “from the interplay of increased sebum production, abnormal follicular keratinization, colonization with Cutibacterium acnes (formerly known as Propionibacterium acnes), and inflammation with contributions from genetic, hormonal, and environmental factors,” the authors wrote.

The gut-skin axis and the human microbiome have garnered increasing attention, generating interest in microbiome-modulatory agents — prebiotics, probiotics, and postbiotics — as potential treatments for acne, senior author Jonette E. Keri, MD, professor of clinical dermatology and cutaneous surgery at the University of Miami Miller School of Medicine, and coauthors noted.

Prebiotics are “nondigestible food ingredients that selectively stimulate beneficial microorganisms in the gut,” while probiotics are “live microorganisms that, when administered in the appropriate amounts, have a positive effect on host health,” the authors wrote. Postbiotics are “inactivated microbial cells, components, or metabolites that exert biological effects without requiring viability.”

The researchers set out to “characterize the safety and efficacy of oral and topical prebiotics, probiotics, and postbiotics in managing acne vulgaris to equip the dermatologist with ample knowledge about the potential role they may play in managing acne.”

They reviewed all randomized controlled trials, cohort studies, and case-controlled studies evaluating these supplements for this indication, beginning with the inception of the databases (PubMed, Embase, Web of Science, and Cochrane) until August 2025. 

A total of 33 studies met the inclusion criteria (2112 patients; aged 18-33 years), with study durations ranging from 4 to 25 weeks. Five studies focused on prebiotics, 24 on probiotics, and seven on postbiotics. Two studies compared prebiotics and probiotics, and one study compared prebiotics and postbiotics to each other. Most of the studies evaluated the effects of the biotic therapies as an addition to standard acne treatments.

Lesion Reductions, Favorable Safety Profile

Most studies “demonstrated acceptable methodological rigor,” although they exhibited “variability across domains,” the authors reported.

They found “favorable” safety profiles across all studies, with no serious adverse events. Lesion reductions were greater for all three interventions compared with controls, with pooled mean total lesion reductions of -37.2% for prebiotics, -45.2% for probiotics, and -49.5% for postbiotics vs -37.0% for the control group.

Although between-group comparisons and route of administration effects didn’t reach statistical significance, within-group improvements were significant for prebiotics (P = .041), probiotics (P < .0001), and postbiotics (P = .0089).

Oral prebiotic formulations containing oligosaccharides, inositol, and polyphenolic complexes were found to improve inflammatory and noninflammatory lesions (-49.3% and -52.7%, respectively). Topical preparations resulted in a -40.3% reduction in total lesions and -21% in inflammatory lesions.

“Prebiotics support the growth of beneficial skin and gut microbes potentially by promoting commensal skin bacteria, inhibiting pathogenic species such as C acnes, and exerting anti-inflammatory and barrier-protective effects,” the authors explained.

Probiotics showed the “strongest and most reproducible clinical efficacy” among the biotic therapies, with reductions of -88.3% and -47.9% for inflammatory and noninflammatory lesions, respectively. Although oral and topical formulations were both effective, oral supplementation showed a “nonsignificant trend” towards a stronger effect. 

“It is theorized that probiotics improve skin barrier hydration through multiple mechanisms including modulation of the skin microbiome, enhancement of barrier protein expression, and production of bioactive metabolites that strengthen the stratum corneum structure and moisture retention capacity,” they suggested.

Postbiotics, which included heat-treated or lysed bacterial preparations and bacterial metabolite creams. demonstrated “signals of benefit for both inflammatory and noninflammatory lesions.” Oral formulations produced stronger effects (mean total lesion reductions of -52% to -58%) compared with topical formulations (-46% to -55% improvement in inflammatory lesions and -40% in noninflammatory lesions). Between-group differences, however, were not statistically significant.

Postbiotics may disrupt C acnes biofilms, suppress lipase activity, and modulate cytokine pathways, the authors speculated. Oral formulations may extend these effects by “engaging systemic host-microbe signaling through the skin-gut-microbiome axis.”

Further research “should prioritize strain- and metabolite-standardized formulations, head-to-head trials, and longer follow-up to establish durability and optimize dosing,” they concluded.

Publication Bias?

Asked to comment on the results, John Barbieri, MD, MBA, associate professor, Harvard Medical School, Boston, and co-chair of the American Academy of Dermatology Acne Guidelines Work Group, raised concerns regarding publication bias. “Research on supplements like prebiotics and probiotics is tricky to interpret,” he told Medscape Medical News. “Since companies will typically only publish studies that show benefit, and as there are likely many companies developing and testing these products for acne, the collection of published studies may paint a more positive picture than the reality if the unpublished studies were included as well.” (Biotic therapy is not mentioned in the latest American Academy of Dermatology guidelines, published in 2024.)

Barbieri, director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, emphasized that it’s “important to have a comprehensive plan when managing acne,” which “can include prescription and over-the-counter treatments, procedures, diet, and supplements.”

He doesn’t generally recommend prebiotics, probiotics, or postbiotics for patients with acne. “For those looking for dietary or nutritional strategies, there is more compelling evidence for approaches such as a low-carbohydrate diet, zinc, and vitamin D. So I will usually start there before considering pre-/pro-/postbiotics.”

Nevertheless, Barbieri considers it “low risk” to try these products, “so long as cost doesn’t become an issue and it doesn’t distract from other more effective options.”

Also commenting on the results, Apple Bodemer, MD, clinical associate professor of dermatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, called it a “really good meta-analysis.”

These types of analyses “have their strengths and weaknesses,” she told Medscape Medical News. Interpreting the results of this array of trials may be “tricky” because it can be “hard to compare systemics and topicals, but the analysis does a nice job of highlighting where we have data and where we don’t.”

Bodemer, also the section chief of dermatology at the VA Hospital, Madison, noted the importance of postbiotics, “which can have a biological effect and significant benefit…and this meta-analysis clearly shows that.” And probiotics “appear to be helpful as an adjunct to standard therapy and also can help decrease some of the side effects of more standard systemic treatments like antibiotics.”

Lastly, the analysis supports the concept of the skin microbiome and the skin-gut connection, Bodemer said.

Barbieri and Bodemer were not involved in the review.

No funding or sponsorship wasreceived for the study or its publication, and the authors declared having no relevant financial relationships. Barbieri reported receiving consulting fees from Alosa Health, Galderma, Honeydew Care, Sagimet Biosciences, Sanofi Pasteur, and Twi Biotechnology. Bodemer reported having no relevant disclosures.

Batya Swift Yasgur, MA, LSW, is a freelance writer with a counseling practice in Teaneck, New Jersey. She is a regular contributor to numerous medical publications, including Medscape and WebMD, and is the author of several consumer-oriented health books as well as Behind the Burqa: Our Lives in Afghanistan and How We Escaped to Freedom (the memoir of two brave Afghan sisters who told her their story).