In the target article, the authors observe that microbiota-gut-brain (MGB) research has gained enormous public attention. We share their concern that public accounts of MGB research tend to force preliminary findings into over-the-counter probiotics or dietary suggestions to improve a broad variety of health outcomes. This appears to reflect a growing appreciation of natural lifestyle habits to oppose the perceived detrimental effects of increased urbanization and declining biodiversity worldwide. The MGB media hype should be considered in line with the sensationalized reporting of neuroscience that complicates social engagement and outreach (Illes et al. Reference Illes, Moser, McCormick, Racine, Blakeslee, Caplan, Hayden, Ingram, Lohwater, McKnight, Nicholson, Phillips, Sauvé, Snell and Weiss2010). Oversimplification of highly complex research and misinterpretation of cardinal concepts such as correlation, causation, and association from widespread media resources can lead to overblown conclusions that negatively impact public health policy. Academic pressure towards public engagement for professionals without specific training in science communication is also likely to contribute. However, the authors’ observations should be interpreted within the broader scope of current shortcomings in translating available biological data to the clinical field of psychiatry. The unprecedented acceleration of neuroscience technology over the past few decades has produced a critically large amount of knowledge that struggles to find its way into everyday practice. The difficulty of replicating findings across patient populations and the lack of significance at the individual level are thought to play a major role in slowing translation (Kapur et al. Reference Kapur, Phillips and Insel2012).

People with severe mental illness (SMI) often show poor nourishment, and the relationship between dietary quality (and possible nutritional deficiencies) and mental health has recently begun to evolve beyond the classical field of cardiometabolic risk studies (Firth et al. Reference Firth, Stubbs, Teasdale, Ward, Veronese, Shivappa, Hebert, Berk, Yung and Sarris2018). One of the mechanisms under scrutiny is the gut-brain axis, a well-demonstrated key player in the combination of activity from immune, endocrine, metabolic, and neural pathways. The potential impact of commensal microorganisms on behavioral symptoms has been extensively studied in patients with irritable bowel syndrome, who often experience co-morbid anxiety and depression. Indeed, several different treatment options, focusing on microbiota manipulation, have been shown to be useful in contrasting the behavioral symptoms in animal models of the disorder (Clarke et al. Reference Clarke, Cryan, Dinan and Quigley2012). Although some studies reported substantial effects of probiotics on emotional processing in healthy women (Tillisch et al. Reference Tillisch, Labus, Kilpatrick, Jiang, Stains, Ebrat, Guyonnet, Legrain-Raspaud, Trotin, Naliboff and Mayer2013), a recent meta-analysis concluded that findings from animal studies have yet to be confirmed in humans (Reis et al. Reference Reis, Ilardi and Punt2018). In neurodevelopmental disorders, several papers recently addressed the question of whether reduced or altered microbial community could affect disease phenotype. Besides changes in microorganisms inhabiting the gut of patients, microbial metabolites have been suggested to actively participate in modulating the clinical severity, but their role is yet to defined (Borghi et al. Reference Borghi, Borgo, Severgnini, Savini, Casiraghi and Vignoli2017; De Angelis et al. Reference De Angelis, Piccolo, Vannini, Siragusa, De Giacomo, Serrazzanetti, Cristofori, Guerzoni, Gobbetti and Francavilla2013; Kang et al. Reference Kang, Ilhan, Isern, Hoyt, Howsmon, Shaffer, Lozupone, Hahn, Adams and Krajmalnik-Brown2018).

In women with anorexia nervosa, a significantly lower total amount of bacteria has been observed compared with age-matched healthy control subjects (Morita et al. Reference Morita, Tsuji, Hata, Gondo, Takakura, Kawai, Yoshihara, Ogata, Nomoto, Miyazaki and Sudo2015). Moreover, these patients showed an altered intestinal microbiota composition, with an unbalanced gram-positive/gram-negative ratio. Modifications in the abundance of microbial communities led to changes in the quantity/quality of microbial metabolites, decreasing the concentration of fecal butyrate, which was found to be negatively related to anxiety and depression symptom scores (Borgo et al. Reference Borgo, Riva, Benetti, Casiraghi, Bertelli, Garbossa, Anselmetti, Scarone, Pontiroli, Morace and Borghi2017).

The gut-brain cross talk has also been investigated in a limited number of patients with schizophrenia at clinical onset (Schwarz et al. Reference Schwarz, Maukonen, Hyytiäinen, Kieseppä, Orešič, Sabunciyan, Mantere, Saarela, Yolken and Suvisaari2018) or in the chronic phase (Shen et al. Reference Shen, Xu, Li, Huang, Yuan, Wang, Zhang, Hu and Liang2018). Both studies found significant changes in patients’ microbial composition compared with control samples.

In our view, MGB research is still in its infancy and should be considered a highly promising tool to disentangle pathways that lead to increased risk for neuropsychiatric syndromes rather than causative in any way. In this light, novel and exciting work has begun to define a mediating role for gut microbiota in well-known mechanisms of neurodevelopmental impairment during pregnancy (Kim et al. Reference Kim, Kim, Yim, Ha, Atarashi, Tan, Longman, Honda, Littman, Choi and Huh2017b). Not unlike other pathogenetic pathways that have been found to overlap across clinical syndromes, MGB research might gain significance within the dimensional Research Domain Criteria (RDoC) framework proposed by the National Institute of Mental Health to overcome the broad overlap of genetics, endophenotypes, and clinical symptoms across disorders (Cuthbert Reference Cuthbert2014). Findings on microbial gut abnormalities are likely to be explained within a network of individual–environment interactions and clinically defined symptom dimensions rather than specific diagnoses.

Finally, although newer technologies have allowed us to tremendously increase our knowledge on the commensal microbial community, Hooks et al. argued that “standard microbiome analyses are not carried out even in many of the most highly cited MGB papers” (sect. 5, para. 4). The authors’ methodological approach, based on selecting the most highly cited papers, resulted in a list of studies ranging from 2004 to 2015. The chosen search methodology left out many papers that employed newer technologies such as 16S rRNA sequencing, shotgun metagenomics, and metabolomics. Furthermore, seven out of nine of the most recent included papers (2013–2015) were sequencing based. Even the most sophisticated technologies (i.e., shotgun metagenomics, allowing both taxa identification and functional characterization of the microbial community) often result in data that are difficult to interpret, highlighting the need for new tools of data integration and correlation (D'Argenio Reference D'Argenio2018). In this light, MGB studies appear to be limited by the intricate relationship between the central nervous system and all other districts, rather than by the lack of standard microbiome analyses as suggested by Hooks et al.

Independent from the applied technique, most studies remain at an observational level, and our understanding of the relationship between complex disorders and abnormalities detected in microbiota and derived microbial metabolites is still mostly speculative.