Background/ObjectivesLive attenuated influenza vaccine (LAIV) protects against influenza by mucosal activation of the immune system. Studies in animals and adults have demonstrated that probiotics improve the immune response to mucosally delivered vaccines. We hypothesized that Lactobacillus GG (LGG) would act as an immune adjuvant to increase rates of seroconversion after LAIV administration.Subjects/MethodsWe conducted a randomized double-blind placebo-controlled pilot study to determine if LGG improved rates of seroconversion after administration of LAIV. We studied 42 healthy adults during the 2007–8 influenza season. All subjects received LAIV and then were randomized to LGG or placebo twice daily for 28 days. HAI titers were assessed at baseline, day 28, and day 56 to determine rates of seroconversion. Subjects were assessed for adverse events throughout the study period.Results39 subjects completed the per protocol analysis. Both LGG and LAIV were well tolerated. Protection rates against the vaccine H1N1 and B strains was similar suboptimal in subjects receiving LGG and placebo. For the H3N2 strain, 84% receiving LGG vs. 55% receiving placebo had a protective titer 28 days after vaccination (odds of having a protective titer was 1.84 95% CI 1.04–3.22, P=0.048).ConclusionLactobacillus GG is potential as an important adjuvant to improve influenza vaccine immunogenicity. Future studies of probiotics as immune adjuvants may need to consider specifically examining vaccine naïve or seronegative subjects, target mucosal immune responses, or focus on groups known to have poor response to influenza vaccines.

A mechanistic understanding of the purported health benefits conferred by consumption of probiotic bacteria has been limited by our knowledge of the resident gut microbiota and its interaction with the host. Here, we detail the impact of a single-organism probiotic, Lactobacillus rhamnosus GG ATCC 53103 (LGG), on the structure and functional dynamics (gene expression) of the gut microbiota in a study of 12 healthy individuals, 65 to 80 years old. The analysis revealed that while the overall community composition was stable as assessed by 16S rRNA profiling, the transcriptional response of the gut microbiota was modulated by probiotic treatment. Comparison of transcriptional profiles based on taxonomic composition yielded three distinct transcriptome groups that displayed considerable differences in functional dynamics. The transcriptional profile of LGG in vivo was remarkably concordant across study subjects despite the considerable interindividual nature of the gut microbiota. However, we identified genes involved in flagellar motility, chemotaxis, and adhesion from Bifidobacterium and the dominant butyrate producers Roseburia and Eubacterium whose expression was increased during probiotic consumption, suggesting that LGG may promote interactions between key constituents of the microbiota and the host epithelium. These results provide evidence for the discrete functional effects imparted by a specific single-organism probiotic and challenge the prevailing notion that probiotics substantially modify the resident microbiota within nondiseased individuals in an appreciable fashion.

BackgroundAlthough Lactobacillus rhamnosus GG ATCC 53103 (LGG) has been consumed by 2 to 5 million people daily since the mid 1990s, there are few clinical trials describing potential harms of LGG, particularly in the elderly.ObjectivesThe primary objective of this open label clinical trial is to assess the safety and tolerability of 1×1010 colony forming units (CFU) of LGG administered orally twice daily to elderly volunteers for 28 days. The secondary objectives were to evaluate the effects of LGG on the gastrointestinal microbiome, host immune response and plasma cytokines.MethodsFifteen elderly volunteers, aged 66–80 years received LGG capsules containing 1×1010 CFU, twice daily for 28 days and were followed through day 56. Volunteers completed a daily diary, a telephone call on study days 3, 7 and 14 and study visits in the Clinical Research Center at baseline, day 28 and day 56 to determine whether adverse events had occurred. Assessments included prompted and open-ended questions.ResultsThere were no serious adverse events. The 15 volunteers had a total of 47 events (range 1–7 per volunteer), 39 (83%) of which were rated as mild and 40% of which were considered related to consuming LGG. Thirty-one (70%) of the events were expected, prompted symptoms while 16 were unexpected events. The most common adverse events were gastrointestinal (bloating, gas, and nausea), 27 rated as mild and 3 rated as moderate. In the exploratory analysis, the pro-inflammatory cytokine interleukin 8 decreased during LGG consumption, returning towards baseline one month after discontinuing LGG (p = 0.038) while there was no difference in other pro- or anti-inflammatory plasma cytokines.Conclusions Lactobacillus rhamnosus GG ATCC 53103 is safe and well tolerated in healthy adults aged 65 years and older.Trial RegistrationClinicalTrials.gov NCT 01274598