Who gets the biggest proven benefit? People with recurrent C. diff infections.
The strongest evidence for microbiome therapeutics is in preventing recurrent Clostridioides difficile infection (rCDI). This is a vicious cycle: antibiotics kill the C. diff bacteria causing the current infection, but they also wipe out protective gut microbes, allowing C. diff spores to germinate and cause another infection. Microbiome therapeutics are designed to restore that protective community. In a pivotal phase 3 trial of the oral spore therapy VOWST (SER-109), only 12% of treated patients had a recurrence within 8 weeks, versus 40% on placebo — a relative risk reduction of 68% [4][7]. An integrated analysis of two phase 3 trials (349 patients total) showed that this benefit held up: the 8-week recurrence rate was just 9.5%, and it stayed low at 15.2% through 24 weeks [2][8]. Another FDA-approved product, fecal microbiota live-jslm (Rebyota), given as a single enema, showed a 70.6% cure rate at 8 weeks versus 57.5% with placebo in its phase 3 trial [3]. A meta-analysis of three randomized controlled trials (469 patients) confirmed that oral microbiome therapy significantly reduces rCDI recurrence at 8 weeks (risk ratio 0.57) with a safety profile similar to placebo [6]. For these patients, the benefit is large, consistent, and backed by multiple high-quality trials.
What about acne, COVID-19, or liver disease? The evidence is much weaker.
For acne, the evidence does not support microbiome therapy. A GRADE systematic review and meta-analysis of five randomized controlled trials involving 332 participants found that Lactobacillus-based probiotics (oral or topical) produced no significant reduction in inflammatory lesions, non-inflammatory lesions, or total lesion counts compared to placebo or benzoyl peroxide [1]. The pooled mean difference for total lesion count was -9.07, but this was not statistically significant (p=0.13), meaning the result could easily be due to chance. This is a clear example where promising theory did not translate into clinical benefit in well-controlled studies.
For COVID-19-related gut dysbiosis, a narrative and systematic review of 27 studies found that probiotics, prebiotics, and fecal microbiota transplantation (FMT) showed positive effects on symptom alleviation, inflammation reduction, and lower mortality (0-11% in intervention groups vs 3-30% in controls) [5]. However, these studies were heterogeneous and mostly small; the review itself notes the evidence is preliminary. For liver disease, including cirrhosis and hepatic encephalopathy, early-phase trials of FMT and defined bacterial consortia have shown safety and some signals of benefit (e.g., improved cognition, reduced hospitalizations), but no large randomized trials have yet proven efficacy [9]. One ongoing trial is testing a defined consortium (VE303) for hepatic encephalopathy, but results are not yet available [9]. So while these areas are active research frontiers, they are not yet ready for clinical use.
Could microbiome therapy one day be personalized? Blood type might matter.
A fascinating study suggests that the effectiveness of microbiome therapy might depend on your blood type. Researchers found that people with blood type A who are also "secretors" (they secrete blood group antigens into body fluids like mucus) have a higher abundance of a beneficial gut bacterium called Faecalibacterium prausnitzii [10]. This bacterium has a gene cluster that lets it use the sugar (GalNAc) found on type A antigens as a nutrient. F. prausnitzii is a major producer of butyrate, a short-chain fatty acid that promotes gut health. This raises the possibility that for microbiome therapies involving F. prausnitzii — whether through diet, probiotics, or FMT — matching the donor strain to the recipient's blood type could improve engraftment and clinical benefit [10]. This is still a research finding, not a clinical recommendation, but it points toward a future where microbiome therapy is tailored to an individual's genetics.
About These Sources
This answer is built on 10 peer-reviewed studies — published from 2022 to 2026, 6 from 2024 or later, 8 in Q1 journals — selected as the most relevant from 10 studies that passed quality screening, drawn from 80 papers retrieved from a database of over 500 million.
Sources used in this answer
Lactobacillus-Based Microbiome Therapy for Acne Vulgaris: A GRADE Systematic Review and Meta-Analysis of Randomized Controlled Trials
A meta-analysis of 5 RCTs (332 participants) found that Lactobacillus probiotics did not significantly reduce acne lesion counts compared to placebo or benzoyl peroxide.
Integrated Safety and Efficacy Analyses of Phase 3 Trials of a Microbiome Therapeutic for Recurrent CDI
An integrated analysis of two phase 3 trials (349 patients) of the oral microbiome therapeutic VOWST (SER-109) for recurrent C. diff showed an 8-week recurrence rate of 9.5%, which remained low (15.2%) through 24 weeks.
Prescription Microbiome Therapeutic for Recurrent Clostridioides difficile Infection: Fecal Microbiota Live-jslm
A review of fecal microbiota live-jslm (Rebyota) for recurrent C. diff reported a 70.6% cure rate at 8 weeks vs 57.5% with placebo in its phase 3 trial, with durable response in >90% of responders at 6 months.
The impact of an oral purified microbiome therapeutic on the gastrointestinal microbiome
A post hoc analysis of phase 3 trials of VOWST (SER-109) showed that the high dose significantly enriched Firmicutes, reduced C. difficile and Enterobacteriaceae, and increased protective secondary bile acids and short-chain fatty acids.
The effect of microbiome therapy on COVID-19-induced gut dysbiosis: A narrative and systematic review
A systematic review of 27 studies found that probiotics, prebiotics, and FMT improved symptoms, reduced inflammation, and lowered mortality in COVID-19 patients, but the evidence is preliminary.
Safety and efficacy of oral microbiome therapy for the treatment of recurrent <i>Clostridioides difficile</i> infection: a systematic review and meta-analysis of randomized controlled trials
A meta-analysis of 3 RCTs (469 patients) found that oral microbiome therapy significantly reduced recurrent C. diff at 8 weeks (risk ratio 0.57) with a safety profile comparable to placebo.
Microbiome therapy for recurrent Clostridioides difficile
A review of phase 3 trials for recurrent C. diff reported that SER-109 (88% recurrence-free) and RBX2660 (70.4% recurrence-free) outperformed placebo, while defined consortia like VE303 and NTCD-M3 also showed promise in phase 2.
Integrated efficacy analysis from phase 3 studies of investigational microbiome therapeutic, SER-109, in recurrent <i>Clostridioides difficile</i> infection
An integrated efficacy analysis of 349 participants from two phase 3 studies of SER-109 showed sustained clinical response rates of 90.5% at week 8 and 84.8% at week 24.
The Current and Future State of Microbiome Therapeutics in Liver Disease
A review of microbiome therapeutics in liver disease found that lactulose and rifaximin are established for hepatic encephalopathy, while FMT and defined consortia (e.g., VE303) are in early trials with safety signals but no proven efficacy yet.
Implications of blood type in personalised microbiome therapy
A genome-wide association study found that people with blood type A who are FUT2 secretors have higher levels of Faecalibacterium prausnitzii, suggesting blood type may influence personalized microbiome therapy.