The findings, published in Nature Medicine, suggest that the therapy is safe and effective at reducing recurrence of C. difficile infection.

Previous studies using fecal microbiota transplants and microbiota-based therapies suggest that restoring gut bacteria could prevent recurrent C. difficile infection. In particular, VOS—an FDA-approved oral microbiota therapy, made of purified Firmicutes spores from healthy donors—has been shown to reduce infection risk compared to traditional fecal transplants. 

However, it’s unclear which specific bacterial species or metabolites are most important, and how VOS prevents recurrent C. difficile infection at a mechanistic level. So, Jessica Bryant at Seres Therapeutics in Cambridge, Massachusetts, and her colleagues conducted a clinical trial testing VOS in people with recurrent C. difficile infection.

Restoring the microbiota

The researchers gave either VOS bacteria or a placebo to 182 people who had recently taken the antibiotic vancomycin and had at least three C. difficile infection. Stool samples were collected before and after treatment to track how VOS bacteria colonized the gut.

Compared with people receiving the placebo, those who received VOS had more beneficial bacterial species appear in their guts, with more protective Firmicutes and fewer Proteobacteria and other disease-associated species. These bacteria stayed in the participants’ guts for at least 24 weeks, the researchers found.

In contrast, people on the placebo had slower and incomplete microbiota recovery, with fewer beneficial bacteria and more harmful species persisting in their guts. Participants who received VOS did not report significant side effects compared to those receiving the placebo.

Preventing recurrence

Before VOS treatment, participants had high levels of primary bile acids and low levels of protective secondary bile acids, a pattern that favors C. difficile growth. After VOS treatment, secondary bile acids and beneficial fatty acids increased rapidly, while primary bile acids decreased. 

Laboratory tests confirmed that these fatty acids can slow or stop C. difficile growth. Similar changes were also produced by VOS bacterial spores outside the body, suggesting that the treatment restores gut metabolites that help block infection, the authors say.“These data support a potential role for VOS, after antibiotic therapy, to restore the microbe-associated metabolic functions needed to prevent [C. difficile infection] recurrence.”

Microbiomepost Microbiomepost.com conducted an exclusive interview with Gianfranco Grompone, Chief Scientific Officer at BioGaia GA to discuss the new evidences about oral microbiome.Distributed across distinct niches such as the tongue, palate, dental plaque, and saliva, the oral microbiome comprises more than 700 microbial species, including bacteria and fungi, organized in resilient biofilms. When this ecosystem shifts toward dysbiosis—often characterized by periodontal pathogens—inflammatory conditions can emerge, including gingivitis and periodontitis, and complications may follow dental procedures such as orthodontic interventions or peri-implantitis. Increasingly, research is also linking the oral microbiome to other body sites, particularly the gut, raising the possibility that oral microbial signatures could serve as proxies for broader systemic health. Emerging evidence suggests associations between specific periodontal pathogens and diseases such as type 2 diabetes, neurological disorders, and colorectal cancer, with Fusobacterium nucleatum frequently cited in this context. Within this landscape, clinically supported probiotics are being investigated as a targeted strategy to modulate oral dysbiosis and inflammation. One approach discussed involves a synergistic combination of Lactobacillus reuteri strains (DSM 17938 and ATCC PTA 5289), developed to reduce periodontal pathogen burden while also attenuating inflammatory processes. More than 70 randomized controlled trials across indications—including gingivitis, periodontitis, peri-implantitis, dental plaque, and caries prevention—were referenced, underscoring the growing role of evidence-based probiotics in oral health.

Franceschi highlights that quantitative and qualitative disruptions of the microbial ecosystem (dysbiosis) can negatively affect immune function, with diet acting as a key modifier: a carbohydrate-heavy, protein-poor pattern may impair antibody-related responses and promote metabolic conditions such as diabetes, which are linked to immune dysfunction and higher infection susceptibility. The interview then focuses on bacterial translocation across a compromised intestinal barrier as a plausible pathway contributing to sepsis. Data from the group’s research indicate that patients with sepsis or septic shock display a distinctly dysbiotic microbiota compared with healthy controls, suggesting that microbial signatures may accompany—or potentially shape—critical illness trajectories. 

Finally, Franceschi reviews preclinical studies investigating probiotic-based strategies (including metabolically relevant bacteria) alongside antibiotics: in animal models, probiotic pre-treatment and continuation during antibiotic therapy have been associated with improved survival compared with antibiotics alone. These findings are encouraging but remain preliminary, underscoring the need for well-designed human trials to assess translatability and clinical impact on sepsis outcomes and mortality.

Day one focused on microbiome-based biomarkers, microbiome testing, and diagnostics, with sessions covering clinical data and the development of diagnostic tools designed to support the use of microbiome biomarkers, including in contexts such as cancer treatment. Day two introduced the conference’s first One Health session, reflecting the expanded scope of the Pharmabiotic Research Institute since 2024 to encompass innovation across One Health and microbiome research. Discussions spanned the plant microbiome, regulation and biocontrol, biofertilizer-related questions, and regulatory developments linked to the emerging “CMC7 list.” A central segment of the program also addressed regulatory updates, including new regulations, the ongoing pharmaceutical revision, and the development of an EME concept paper on live biotherapeutic products, with regulators present in the room—one of the conference’s key added values for fostering informed debate. The final day featured a session on clinical development and innovation, including presentations from Exelium and Microbiotica and a panel discussion integrating development and regulatory perspectives. Organizers announced that the 2027 edition is planned for the same period next year, likely again in Belgium.

In this interview, the Ojetti presents findings from a single-center pilot study assessing the effects of Limosilactobacillus reuteri LMG P-27481 on the gut microbiota and selected markers of intestinal barrier function in healthy individuals. The strain is described as patented and characterized by a favorable safety profile (no plasmid transfer and antibiotic susceptibility), with potential anti-inflammatory features including increased interleukin-10. It was administered as drops (5 drops/day) for 28 consecutive days. Twenty healthy volunteers (10 men and 10 women; median age ~35 years) were enrolled at the San Carlo di Nancy Hospital in Rome. Stool samples and gastrointestinal symptom questionnaires were collected at baseline, at the end of treatment, and after a 14-day follow-up period following discontinuation. After 28 days, the interview reports a reduction in intestinal permeability and an improvement in barrier function, consistent with prior evidence suggesting L. reuteri may help modulate permeability. However, 14 days after stopping supplementation, these parameters tended to return toward baseline—interpreted as a reflection of microbiota resilience. 

From a functional standpoint, the interview highlights an increase in short-chain fatty acid production, particularly butyrate, with a reported rise from 10% to 40% after treatment, aligning with a potential anti-inflammatory effect and barrier-supporting activity; this signal also diminished during follow-up. Ojetti also mentions shifts in specific taxa and an increase in tryptophan production, which is framed as consistent with earlier observations proposing a possible “psychobiotic” profile for L. reuteri. Clinically, despite the largely healthy population, the interview points to significant improvements in abdominal bloating and the sensation of gas/air, alongside signs of bowel habit normalization: increased bowel movements in participants reporting constipation and fewer stools in those reporting looser or more frequent bowel habits. 

Overall, these preliminary results suggest beneficial but potentially transient effects, supporting the need for larger studies and for longer or cyclical dosing strategies to evaluate whether benefits can be sustained over time.

The interview highlights how the gut microbiota can become a clinical tool on three levels: identifying and stratifying patients, clarifying pathogenic mechanisms, and opening up new therapeutic options. In patients with cirrhosis, a typical pattern is a reduction in “beneficial” bacteria (with decreases in taxa such as Faecalibacterium prausnitzii, Akkermansia, and bifidobacteria, along with autochthonous groups such as Lachnospiraceae and Ruminococcaceae) and, in parallel, an increase in potentially pathogenic and oral-derived microbes—often interpreted as a sign of impaired compartmentalization along the gastrointestinal tract. Specific microbial “signatures” also appear to be associated with distinct clinical settings, from MASLD (formerly NAFLD) to alcohol-related liver disease, with potential applications in prognosis and precision medicine—for instance, stratifying patients with hepatocellular carcinoma undergoing immunotherapy or identifying those at higher risk of developing complications. Mechanistically, the microbiota contributes to the production of clinically relevant enzymes and metabolites: from urease, involved in ammonia metabolism, to compounds linked to hepatic encephalopathy; in MASLD, metabolites such as ethanol and choline-derived products also play a role, with implications not only for progression toward steatohepatitis and fibrosis but also for cardiovascular risk. 

Finally, Ponziani underscores the therapeutic promise of microbiota modulation: fecal microbiota transplantation emerges as a particularly promising option—especially for hepatic encephalopathy—with encouraging data also for oral capsule delivery and a favorable safety profile. Looking ahead, next-generation probiotics and targeted molecules designed to interrupt pathological gut–liver signaling may expand the therapeutic armamentarium for obesity and severe syndromes such as acute-on-chronic liver failure.

The discussion focuses on Saccharomyces cerevisiae, a microorganism historically associated with food fermentation (bread, beer, and wine), now reconsidered through two decades of advances in cell-wall biology and genetics. A central concept is that cell-wall architecture—especially the chitin-to-mannan balance—may influence the activation of distinct immune responses, supporting a rational approach to strain selection and to distinguishing beneficial strains from potentially harmful ones.

The interview also revisits a common critique of S. cerevisiae probiotics: limited intestinal colonization. Rather than being a drawback, transient passage is presented as a potential ecological advantage, helping to promote the growth of Lactobacillus species relevant not only for gut health but also for vaginal and skin ecosystems, while counteracting overgrowth of key enteric pathobionts and pathogens such as Klebsiella, Escherichia coli, and Shigella. From this perspective, future probiotic consortia may intentionally include selected Saccharomyces strains as functional members of a broader microbial ecosystem. Finally, Saccharomyces boulardii—widely used for traveler’s diarrhea—is framed as merely the “tip of the iceberg,” pointing to a broader, still underexplored yeast-based probiotic pipeline.

The global probiotic supplements market reached $9.4 billion in 2024, with historical growth around 9.5% and a projected slowdown to ~6% CAGR over the next four years—a dip attributed to broader economic uncertainty, with expectations that forecasts may rebound as new data emerges for 2025–2027. 

Regionally, APAC leads at ~$3.7B, driven largely by China (about 55% of APAC) and double-digit growth, positioning it as a rapidly dominant market. The Americas total ~$3.2B, where the U.S. accounts for ~80%, but growth trails China’s pace. Europe, while the third-largest region (~25% of the global market), shows a notable “paradox”: it ranks among the strongest for e-commerce growth, suggesting high consumer demand alongside persistent confusion about product choice and even basic definitions (including probiotics vs. prebiotics vs. postbiotics). The interview highlights how less-regulated online platforms can amplify misinformation and marketing-driven purchasing. A central barrier remains regulatory divergence, with identical products classified differently across countries (drug, supplement, food, or medical device), complicating commercialization and increasing the need for robust regulatory strategies amid rising evidence and tightening hurdles.

Probiotic research is frequently constrained not by lack of scientific interest, but by the difficulty of generating evidence that satisfies the European Food Safety Authority (EFSA) for authorized health claims. 

From a regulatory standpoint, the first obstacle is trial design: the intended benefit must be matched to an appropriate target population and measurable endpoints. Claims framed around prevention or risk reduction in healthy individuals often require very large cohorts and long follow-up to demonstrate a statistically and clinically meaningful effect, making such studies logistically and financially prohibitive. By contrast, efficacy may be more feasibly demonstrated in well-defined patient populations with established gastrointestinal conditions (for example, inflammatory bowel disease), after which the relevance of these findings to broader preventive contexts can be explored.

According to Rijkers, a second obstacle is conceptual. EFSA’s assessment model has historically been better suited to single, well-characterized molecules (e.g., vitamins) with clearer mechanistic links to host receptors and pathways. Probiotics, as live microorganisms, act through multiple interacting components and indirect host responses, which complicates mechanistic substantiation and evidence integration. Finally, probiotics are regulated as foods and supplements rather than drugs, which shapes expectations around study settings and participant selection and can limit the types of trials that are considered acceptable. Although EFSA authorization is theoretically attainable, a long record of negative opinions—combined with limited prescriptive guidance and reliance on case-by-case evaluation—creates substantial uncertainty for dossier development and clinical strategy, suggesting that progress will require not only stronger evidence but also clearer regulatory direction.