Benefits
Days with seasonal symptoms in healthy older adults
In a 4 month winter trial in 100 healthy adults aged 60 to 74, 2 billion spores a day in four 10 day courses did not significantly reduce days with infection symptoms, the main outcome (5.1 versus 6.6 days). The number of respiratory infections and the share of people with at least one did not differ in the whole group. The maker took part in running and funding the trial.
Respiratory infections in a sampled trial subset
In the 44 trial participants who gave samples, the CU1 group had fewer respiratory infections than placebo (0.6 versus 1.1 per person). This was an unplanned analysis of a subset set up for lab tests, it was not seen in the full group of 100, and the authors say it may be due to chance and that no firm conclusion can be drawn.
Stool and saliva IgA, immune markers
In the 44 older adults who gave samples, secretory IgA in stool and in saliva was higher on CU1 than on placebo at the end of the trial; blood interferon gamma rose after the first course within the CU1 group but did not differ from placebo, and other blood cytokines and serum IgA did not change. In a later 4 week study with no placebo group, stool IgA, its main outcome, did not change.
Blood immune cell activity in a 4 week open study
In 88 children, adults and older adults given 2 billion CFU a day for 4 weeks with no placebo group, adults and older adults showed more blood myeloid cells, higher CD69 on monocytes, stronger cytokine output when blood was stimulated in the lab and greater uptake of bacteria by monocytes. These are lab markers measured before and after, in a study run by the maker.
Spore passage through the gut
In the older adult trial, Bacillus spore counts in stool rose from about 2.5 thousand to about 19 million after 10 days of CU1, and the strain was identified in stool by DNA testing, while the placebo group did not change. Counts fell back after the break, and stool samples showed no toxic effect on cultured cells.
Combination product with Saccharomyces boulardii in young children
A combination sachet of S. boulardii CNCM I-3799 and 1 billion CFU of CU1 was tested against placebo in 180 Indian children aged 6 months to 5 years with acute watery diarrhea. Average duration differed by about 5 hours overall, and a 14 hour gap was significant only in the 85 children dosed within 48 hours of onset. This is not evidence for CU1 on its own.
Mechanism of action
Mucosal IgA and blood immune signals (human markers)
CU1 is proposed to act on gut immune tissue: in older adults stool and saliva IgA ended higher than on placebo and blood interferon gamma rose within the CU1 group only, and an open study reported changes in blood monocyte activity. These markers were not shown to change infection outcomes in the full trial.
Colon water and salt transport (animal work)
In mice given castor oil or a bacterial toxin to induce watery stools, prior CU1 dosing reduced water loss, blocked the toxin's rise in gut leakiness and shifted colon levels of the CFTR channel and the NHE3 exchanger in a direction that favors water absorption. This was a study coauthored by Lesaffre staff and has not been tested in people.
Cell wall and sugar compounds (lab work)
Purified lipoteichoic acid from CU1's cell wall triggered nitric oxide release by mouse immune cells, an effect that depended on its D-alanine groups. A levan sugar made by CU1 blocked one human norovirus type in zebrafish larvae but not two others. In a gut content model CU1 did not reduce drug-resistant E. coli and lacked the antimicrobial peptide genes found in two other strains.
Clinical trials
Randomized, double-blind, placebo-controlled parallel trial; one capsule of 2 billion CU1 spores or placebo a day in four 10 day courses separated by 18 day breaks over 4 months; run by Biofortis (Mérieux NutriSciences); partly financed by a French government research program and supported by a regional research cluster and Lesaffre, which made the product; the first author worked for a Lesaffre subsidiary and another author for Lesaffre Human Care; no registry number given in the paper; further safety results published in 2017 (Lefevre et al. 2015, Immun Ageing)
100 healthy adults aged 60 to 74 (about 80 percent women) with at least two common infections the previous winter; 50 per group, with blood, saliva and stool tested in the first 44 enrolled.
Null primary result: days with common infection symptoms did not differ (5.1 versus 6.6 days, P = 0.2015), nor did respiratory infection frequency (0.7 versus 1.1, P = 0.1181) or the share with a respiratory infection (48 versus 62 percent) in all 100. In the 44 person subset, stool IgA (P = 0.0032) and saliva IgA (P = 0.0219) were higher on CU1 than on placebo at study end, serum interferon gamma rose within the CU1 group only (P = 0.0090; between groups P = 0.0981), and an unplanned analysis found fewer respiratory infections (P = 0.0323). Adverse events numbered 108 on CU1 and 85 on placebo (P = 0.8369).
Open-label, single-group study with no placebo or control group (NCT05403398); 2 billion CFU a day for 4 weeks; sponsored by Lesaffre International with NIZO Food Research; six of eleven authors worked for Gnosis by Lesaffre or the Lesaffre Institute of Science and Technology (Mourey et al. 2024, Benef Microbes)
88 healthy participants in three age groups: children aged 3 to 6, adults aged 30 to 49 and older adults aged 65 to 79 (89 enrolled per the registry).
Null primary result: stool secretory IgA did not change. Before and after comparisons in adults and older adults showed more blood myeloid cells, higher CD69 on monocytes, interferon and phagocytosis gene activity, more cytokine release when blood was stimulated with bacterial LPS and greater bacterial uptake by monocytes; in older adults, resting serum IL-10, TNF-alpha, MIP-1alpha and IL-8 fell. With no placebo group, these changes cannot be credited to CU1.