Published in Antibiotics, the research indicated the synbiotic, marketed as DS-01, significantly increased the diversity of Bifidobacterium and Lactobacillus species at all measured timepoints. This led to a substantial increase in beneficial microbiome-derived metabolites such as butyrate, fecal acetate, and urolithin A.
The daily synbiotic also appeared to lower intestinal permeability compared to placebo both immediately after antibiotics and in the long-term.
Study author Gregor Reid, professor emeritus at the University of Western Ontario, Canada, said the findings refute the idea that probiotics do not confer a benefit following antibiotic exposure—a belief that became popularized in 2018 after a paper by Suez et al. reported that a probiotic formulation delayed the recovery of the microbiome after antibiotics.
“It was such a shame that [the media] jumped on the Suez et al. Cell paper in 2018 comprising a handful of subjects and ridiculously suggested that probiotics (as a general term) were not effective after antibiotics and might even make the gut microbiome worse,” he told NutraIngredients. “This was rightly criticized at the time but the damage had been done.”
“It took a while to perform a study countering this but the recent paper in Antibiotics, in my view, clearly shows those 2018 articles were far off the mark, and the 24-strain synbiotic supports the preservation and recovery of microbiome community structure and key microbiome functions while promoting gut barrier function following antibiotics. The additional finding of significant depletion of a toxin involved in kidney and heart disease further emphasizes the point.”
The problem with antibiotics
Broad-spectrum antibiotics significantly disrupt the gut microbiome, resulting in loss of taxonomic diversity and depletion of keystone microbes. This often manifests with gastrointestinal symptoms such as diarrhea, bloating and abdominal discomfort.
Probiotics have emerged as a promising tool to prevent these negative effects, yet study results have varied greatly. This may be due to differences in design, including strain selection, the inclusion of a prebiotic, delivery format, timing relative to antibiotics and the endpoints evaluated, according to Dr. Zain Kassam, Chief Medical Officer at Seed Health.
“Not all probiotics work the same way,” Dr. Kassam told NI. “Formulation matters—the specific strains, doses, prebiotic pairing and delivery system all impact outcomes.”
DS-01 is formulated with 24 scientifically studied strains including multiple Bifidobacterium and Lactobacillus species. The prebiotic component is a non-fiber, polyphenol-based extract from Indian pomegranate chosen for its ability to produce bioactive metabolites, such as urolithin A.
“We used microbial genomics to map every gene in DS-01 with unprecedented depth and clarity,” explained Dr. Kassam. “The goal was to maximize both genetic redundancy and non-redundancy—meaning strains that provide backup functions while also offering unique capabilities. This creates a resilient ecosystem where strains work synergistically to address multiple mechanisms that affect digestive health.”
DS-01 is engineered with ViaCap, a capsule-in-capsule delivery system that safeguards probiotics against stomach acid to ensure they are released in the colon. The capsule also serves as a barrier to oxygen, moisture and heat stress, meaning the synbiotic can withstand fluctuating temperatures.
In this study, the researchers set out to discover whether DS-01 could accelerate the restoration of microbiome diversity and restore gut barrier integrity following a course of antibiotics.
Study details
To conduct their study, researchers from Seed Health, Harvard Medical School and Yale University (among others) randomized 31 healthy adults into two groups: an intervention group and a placebo group.
All participants received a seven-day course of two types of antibiotics: ciprofloxacin and metronidazole. Participants then received either the synbiotic or a placebo (rice flour) to take daily for 91 days.
Alpha-diversity of Bifidobacterium and Lactobacillus species was significantly higher in the intervention arm compared to the placebo group both immediately after cessation of antibiotics and during the recovery period. Levels of the butyrate-producing microbe Clostridium butyricum were also significantly higher in the supplementation arm compared to placebo.
This resulted in a 119% increase in butyrate levels among those taking DS-01, with fecal acetate and urolithin A levels also increasing by 62% and 13,008%, respectively. These significant increases reflect low baseline levels, the authors pointed out.
Levels of some harmful species of bacteria also decreased post-intervention. For example, Phocaeicola vulgatus, a native pathobiont, decreased after antibiotics. The synbiotic significantly suppressed the recovery of P. vulgatus after antibiotics compared to placebo, and the result persisted through to day 91.
To measure changes to gut permeability, the researchers assessed the recovery of urinary lactulose, a disaccharide that is non-metabolizable or absorbable by humans. Using this test, they found that the synbiotic increased gut barrier integrity by roughly 50% compared to placebo both during and after antibiotics.
The researchers say the results provide “compelling evidence” that DS-01 supports the preservation and recovery of the gut microbiome and gut barrier function following antibiotics. However, further research is needed to determine whether similar results would be seen in wider, more diverse populations, and in those taking other classes of antibiotics.
Dr. Kassam also highlighted that the benefits are likely to wear off once supplementation ceases, suggesting the need for continuous, long-term synbiotic supplementation.
“Probiotics are naturally transient—they don’t permanently colonize the gut, and that’s actually by design,” he said. “They provide benefits as they pass through the digestive system, interacting with immune cells, gut lining, and native bacteria before exiting the body. As such, we always recommend continuous daily supplementation to maintain benefits.”
Source: Antibiotics. doi: 10.3390/antibiotics15020138. “Multi-Species Synbiotic Supplementation After Antibiotics Promotes Recovery of Microbial Diversity and Function, and Increases Gut Barrier Integrity: A Randomized, Placebo-Controlled Trial.” Authors: B. Napier, et al.
