Rationale: Viral illnesses in children are common and are frequently treated with antibiotic medication. Antibiotics reduce the diversity and composition of the gut microbiota, leading to poor developmental outcomes. Objectives: To investigate the relationship between age at first exposure to antibiotics and cognitive and behavioural development at 4.5 years while controlling for multiple confounders, including otitis media. Methods: Study participants were 5589 children enrolled in the broadly generalisable Growing Up in New Zealand cohort study, with antibiotic exposure data, maternal antenatal information, and age 4.5-year behaviour and cognitive outcome data. Children were categorised as first exposed to antibiotics according to the following mutually exclusive ages: 0–2 months; 3–5 months; 6–8 months; 9–11 months; 12–54 months or not exposed by 54 months. Developmental outcome measures included the Strengths and Difficulties Questionnaire, Luria hand clap task, and the Peabody Picture Vocabulary Test-III. Results: In univariate analysis, there was an evident dose–response relationship where earlier exposure to antibiotics in the first year of life was associated with behavioural difficulties, lower executive function scores, and lower receptive language ability. After adjusting for confounders, pairwise comparisons showed that first antibiotic exposure between birth and 3 months or between 6 and 9 months was associated with lower receptive vocabulary. Antibiotic exposure at any age prior to 12 months was associated with increases in behavioural difficulties scores at 4.5 years. Conclusions: Following adjustment for socioeconomic factors and otitis media, there is evidence that antibiotic exposure during potentially sensitive windows of development is associated with receptive language and behaviour later in childhood.

Animal studies demonstrate how the gut microbiota influence psychological health and immunity to viral infections through their actions along multiple dynamic pathways in the body. Considerable interest exists in probiotics to reduce stress and illness symptoms through beneficial effects in the gut, but translating pre-clinical evidence from animal models into humans remains challenging. We conducted a large trial in nurses working during the 2020 COVID19 pandemic year to establish whether daily ingestion of the probiotic Lactobacillus rhamnosus HN001 reduced perceived stress and the number of days participants reported symptoms of a viral illness. Our results showed no significant difference in perceived stress or the average number of illness days between probiotic supplemented nurses and the placebo group. Stress and viral illness symptoms reduced during the study for all participants, a trajectory likely influenced by societal-level factors. The powerful effect of a well-managed public health response to the COVID19 pandemic and the elimination of COVID19 from the community in 2020 may have altered the trajectory of stress levels and reduced circulating viral infections making it difficult to detect any effect of probiotic supplementation. Our study highlights the challenge in controlling environmental factors in human trials.

Background: Studies suggest that bioactive compounds such as probiotics may positively influence psychological health. This study aimed to determine whether supplementation with the probiotic Lacticaseibacillus rhamnosus HN001 reduced stress and improve psychological wellbeing in university students sitting examinations. Methods: In this randomized, double-blind, placebo-controlled study, 483 undergraduate students received either the probiotic L. rhamnosus HN001, or placebo, daily during a university semester. Students completed measures of stress, anxiety, and psychological wellbeing at baseline and post-intervention before examinations. Mann Whitney U tests compared the change in psychological outcomes between groups. Results: Of the 483 students, 391 (81.0%) completed the post-intervention questions. There was no significant difference between the probiotic and placebo supplemented groups in psychological health outcomes. The COVID19 pandemic restrictions may have influenced the typical trajectory of stress leading up to examinations. Conclusion: We found no evidence of significant benefit of probiotics on the psychological health of university students. These findings highlight the challenges of conducting probiotic trials in human populations where the potential for contextual factors such as COVID19 response, and participant adherence to the intervention may influence results.