Early-life microbial exposures shape immune development and allergy risk. Food allergen sensitization, reflected by the presence of food allergen-specific immunoglobulin E (IgE), is an early indication of impaired immune tolerance. Here we show that early-life transmission of aromatic lactate-producing bifidobacteria strains in 147 children followed from birth to 5 years of age, facilitated by vaginal delivery, exposure to older siblings and exclusive breastfeeding for the first 2 months, led to increased levels of aromatic lactates in the infant gut. This microbiota–metabolite signature was inversely associated with the development of food allergen-specific IgE until 5 years and atopic dermatitis at 2 years. The observed effect was mediated by 4-hydroxy-phenyllactate, which inhibited IgE, but not IgG, production in ex vivo human immune cell cultures. Together, these findings define an early-life microbiota–metabolite–immune axis linking microbial transmission and feeding practices with reduced allergic sensitization.

Despite the critical role of the gut resistome in spreading of antimicrobial resistance (AMR), strategies to reduce the abundance of antibiotic resistance genes (ARGs) during microbiota development in infancy remain underexplored. Using longitudinal quantitative metagenomic data, we here show that ARGs are present in the gut microbiota from the first week of life, with a peak in absolute ARG abundance and richness at 6 months. Delivery mode significantly affects early ARG dynamics, and vaginally delivered infants exhibit higher ARG abundance due to maternal transmission of Escherichia coli strains harbouring extensive resistance repertoires. The abundance of E. coli and other ARG-rich taxa inversely correlates with aromatic lactic acid-producing bifidobacteria, and aromatic lactic acids strongly inhibit the in vitro growth of E. coli and other opportunistic ARG-rich taxa. Our results highlight temporal and critical microbial interactions shaping the gut resistome in early infancy, pointing to potential interventions to curb AMR during this vulnerable developmental window by promoting colonization of aromatic lactic acid-producing bifidobacteria.

Background In the European Union (EU), the safety assessment of plant protection products relies to a large extent on toxicity studies commissioned by the companies producing them. By law, all performed studies must be included in the dossier submitted to authorities when applying for approval or renewal of the active substance.

Methods For one type of toxicity, i.e. developmental neurotoxicity (DNT), we evaluated if studies submitted to the U.S. Environmental Protection Agency (EPA) had also been disclosed to EU authorities.

Results We identified 35 DNT studies submitted to the U.S. EPA and with the corresponding EU dossiers available. Of these, 9 DNT studies (26%) were not disclosed by the pesticide company to EU authorities. For 7 of these studies, we have identified an actual or potential regulatory impact.

Conclusions We conclude that (1) non-disclosure of DNT studies to EU authorities, in spite of clear legal requirements, seems to be a recurring phenomenon, (2) the non-disclosure may introduce a bias in the regulatory risk assessment, and (3) without full access to all performed toxicity studies, there can be no reliable safety evaluation of pesticides by EU authorities. We suggest that EU authorities should cross-check their data sets with their counterparts in other jurisdictions. In addition, applications for pesticide approval should be cross-checked against lists of studies performed at test facilities operating under Good Laboratory Practice (GLP), to ensure that all studies have been submitted to authorities. Furthermore, rules should be amended so that future studies should be commissioned by authorities rather than companies. This ensures the authorities’ knowledge of existing studies and prevents the economic interest of the company from influencing the design, performance, reporting and dissemination of studies. The rules or practices should also be revised to ensure that non-disclosure of toxicity studies carries a significant legal risk for pesticide companies.

The stable nitrogen isotope ratio δ¹⁵N is used as a marker of dietary protein sources in blood. Crop fertilization strategies affect δ¹⁵N in plant foods. In a double-blinded randomized cross-over dietary intervention trial with 33 participants, we quantified the effect of fertilizer type (conventional: synthetic fertilizer and organic: animal or green manure) on δ¹⁵N in blood plasma. At study baseline, plasma δ¹⁵N was +9.34 ± 0.29‰ (mean ± standard deviation). After 12 days intervention with a diet based on crops fertilized with animal manure, plasma δ15N was shifted by +0.27 ± 0.04‰ (mean ± standard error) compared to synthetic fertilization and by +0.22 ± 0.04‰ compared to fertilization with green manure (both p < 0.0001). Accordingly, differences in the δ¹⁵N values between fertilizers are propagated to the blood plasma of human consumers. The results indicate a need to consider agricultural practices when using δ¹⁵N as a dietary biomarker. 

The safety evaluation of pesticides in the European Union (EU) relies to a large extent on toxicity studies commissioned and funded by the industry. The herbicide glyphosate and four of its salts are currently under evaluation for renewed market approval in the EU. The safety documentation submitted by the applicant companies does not include any animal study regarding developmental neurotoxicity (DNT) that is compliant with test guidelines. For a fifth salt, not included in the present application for re-approval, such a DNT study was sponsored by one of the applicant companies in 2001. That study shows an effect of that form of glyphosate on a neurobehavioural function, motor activity, in rat offspring at a dose previously not known to cause adverse effects. Counter to regulatory requirements, these effects were apparently not communicated to authorities in EU countries where that form of glyphosate was authorised at that time. That DNT study may also be relevant for the ongoing assessment of glyphosate but was not included in the present or previous applications for re-approval. In this commentary, we highlight that it is the responsibility of the industry to evaluate and ensure the safety of their products, taking all available scientific knowledge into account. We argue that the legal obligation for industry to submit all potentially relevant data to EU authorities is clear and far-reaching, but that these obligations were not fulfilled in this case. We claim that authorities cannot reliably pursue a high level of protection of human health, if potentially relevant evidence is withheld from them. We suggest that a retrospective cross-check of lists of studies performed by test laboratories against studies submitted to regulatory authorities should be performed, in order to investigate the completeness of data submitted to authorities. We further suggest that future toxicity studies should be commissioned by authorities rather than by companies, to improve the authorities’ oversight over existing data and to prevent that economic conflicts of interest affect the reporting of study results and conclusions. 

The influence of organic and conventional farming practices on the content of single nutrients in plants is disputed in the scientific literature. Here, large-scale untargeted LC-MS-based metabolomics was used to compare the composition of white cabbage from organic and conventional agriculture, measuring 1,600 compounds. Cabbage was sampled in 2 years from one conventional and two organic farming systems in a rigidly controlled long-term field trial in Denmark. Using Orthogonal Projection to Latent Structures–Discriminant Analysis (OPLS-DA), we found that the production system leaves a significant (p = 0.013) imprint in the white cabbage metabolome that is retained between production years. We externally validated this finding by predicting the production system of samples from one year using a classification model built on samples from the other year, with a correct classification in 83 % of cases. Thus, it was concluded that the investigated conventional and organic management practices have a systematic impact on the metabolome of white cabbage. This emphasizes the potential of untargeted metabolomics for authenticity testing of organic plant products.