The gut microbiome has recently emerged as an important new player in our efforts to understand the different factors that influence human behaviour (McVey Neufeld et al. Reference McVey Neufeld, Luczynski, Seira Oriach, Dinan and Cryan2016; Sarkar et al. Reference Sarkar, Lehto, Harty, Dinan, Cryan and Burnet2016; Tang et al. Reference Tang, Reddy and Saier2014). Gut and brain are intimately connected via the gut-brain axis, which involves bidirectional communication via neural, endocrine, and immune pathways (Grenham et al. Reference Grenham, Clarke, Cryan and Dinan2011; Grossman Reference Grossman1979; Mayer et al. Reference Mayer, Knight, Mazmanian, Cryan and Tillisch2014). Research in both human and animal models has also highlighted the important role that gut microbiota play in regulating the brain and subsequent behaviour, particularly within the context of mental health problems such as anxiety or depression (Cryan & Dinan Reference Cryan and Dinan2012; Foster & McVey Neufeld Reference Foster and McVey Neufeld2013; Mayer Reference Mayer2011).

It is not surprising, therefore, that the microbiome, and its effect on behaviour and mental health, has captured the interest and imagination of scientists and the wider public alike. As a result, research in this relatively new area has intensified, as have funding opportunities that aim to close the many gaps in our understanding. The substantial translational potential of this research and the opportunities to establish links with industry may also play a significant role in this development. In their target article, Hooks et al. highlight the enormous potential that the new area of microbiota-gut-brain (MGB) axis research holds for understanding human behaviour, yet they also rightly point towards several concerns in research practice that are not necessarily specific to the field of MGB research but are of relevance to broader scientific practice in examining human behaviour. The greatest concern is that public expectations and commercial efforts have already overtaken the relatively small number of research publications to date, and there is a significant risk of backlash if the foundations of the young MGB field prove to be less than beneficial.

So how can the combination of human development and MGB research contribute to mental health research and interventions? It has been shown that a significant reduction in microbial diversity in the gut, known as dysbiosis, affects brain-behaviour relationships and may lead to psychological abnormalities, as common in mental illness (Foster & McVey Neufeld Reference Foster and McVey Neufeld2013). In adults, for example, dysbiosis has been shown to be related to symptoms of anxiety and depression (Mayer Reference Mayer2011; Mayer et al. Reference Mayer, Knight, Mazmanian, Cryan and Tillisch2014). Most importantly, animal research has repeatedly shown that the timing of dysbiosis is important, and that the period of adolescence may be a critical window during development where microbiota help fine-tune the gut-brain axis related to stress responses and anxiety (Foster & McVey Neufeld Reference Foster and McVey Neufeld2013). This suggests that the consequences of dysbiosis will be particularly critical during development, as ongoing maturation and increased plasticity levels can lead to atypical behavioural patterns and brain network maturation (Cohen Kadosh & Johnson Reference Cohen Kadosh and Johnson2007; Cohen Kadosh et al. Reference Cohen Kadosh, Linden and Lau2013). The psychiatric literature supports this hypothesis: Age-of-onset data show that first symptoms of many psychiatric disorders, including (social) anxiety or depression emerge at the adolescent juncture (Keshavan et al. Reference Keshavan, Giedd, Lau, Lewis and Paus2014; Kessler et al. Reference Kessler, Berglund, Demler, Jin, Merikangas and Walters2005). We therefore believe that MGB research could provide the missing link that brings together previous research in human brain development and mental health.

We believe that it is now important to take advantage of the promising findings in animal-model research to investigate whether similar effects of the timing and effects of dysbiosis also apply to the human model and to investigate the psychoactive properties of the microbiome in the transition from childhood to adulthood. Animal models suggests that one way of influencing microbial diversity and reversing dysbiosis is via nutrition, and it has been shown that drastic changes in diet can alter microbial diversity in mere days (David et al. Reference David, Maurice, Carmody, Gootenberg, Button, Wolfe, Ling, Devlin, Varma, Fischbach, Biddinger, Dutton and Turnbaugh2014). This opens up new opportunities for both prevention and intervention, but more research is still needed to show how we can benefit from this window of plasticity to shape the developmental trajectories in at-risk groups.

Here, we would like to draw attention to the important contribution that developmental cognitive neuroscience (DCN) research can make for establishing causal relationships between dysbiosis and mental health problems during the critical developmental period when the gut-brain axis is fine-tuned and when atypical patterns will have long-lasting consequences. The DCN research approach focuses on investigating how the complex interplay of genetic, environmental, and brain maturational factors shape psychological functioning in development to improve the outcome for the individual (Cohen Kadosh Reference Cohen Kadosh2011; Johnson et al. Reference Johnson, Halit, Grice and Karmiloff-Smith2002; Reference Johnson, Grossmann and Cohen Kadosh2009). Moreover, placed at the intersection of nature versus nurture, the DCN research approach always assumes a multilevel and multifactor approach to understanding change, which, by definition, is multidisciplinary. Given that the field of microbiome and gut-brain axis research is still emerging and finding its shape, we are strongly convinced that any real progress will depend on the adoption of a similarly comprehensive multifactorial and multidisciplinary research approach for pinpointing mechanisms and translation in both animal and human models. Such an approach would also be able to account for specific critical periods in development, when change happens at many levels simultaneously. We therefore agree with the authors that discussion must be given to specifying mechanisms, differentiating correlational from causal explanations, and addressing a priori realistic outcomes. Moreover, there needs to be rigorous assessment in human populations, coupled with well-defined research questions and appropriate statistical analysis. This is particularly important given that strong public and commercial interests are presently outpacing research efforts. Based on an extensive body of research in the field of DCN, we are aware that even simple changes in behaviour or diet can have long-lasting effects on the brain, and mental health and well-being, all of which need to be considered as the ethical implications are significant. Therefore, to maintain current momentum and to future-proof the field of MGB research, a multidisciplinary research approach such as currently practised in the field of DCN is key if we want to reach our aims of translation and targeted intervention approaches to improve mental health and well-being.