The extensive review by Hooks et al. provides a critical analysis of the many claims that are made about the relationships between gut, microbiota, and human behavior. The authors do not deny that the research field of microbiota-gut-brain (MGB) is very important, and neither do they reject the many amazing results from animal studies. The main conclusion they present, supported by convincing evidence, is the oversimplification and overselling of animal findings in MGB research and the suggested far-reaching implications for human mental health. Interestingly, and in accordance with Hooks et al., the European Food Safety Authority did not award any claim of probiotics on physical or mental health (European Commission 2016). We agree, that in the long term, overblown claims damage the scientific credibility of MGB research, and that this may contribute to the erosion of the public's trust in science. We would like to add another concern, namely, that of the reduced support of animal testing by the general public when false claims based on animal experiments cannot be replicated in human studies. Another problem that has also been addressed by Hooks et al. is the use of animal models of mental disorders, where healthy or germ-free animals are used, which do not explain or mimic pathological mechanisms in ill psychiatric patients. In these animal models, behavioral findings could easily have been explained in terms of coping mechanisms (Korte et al. Reference Korte, Koolhaas, Wingfield and McEwen2005). In addition, stress hormones are not necessarily bad; they serve the process of healthy adaptation (Korte et al. Reference Korte, De Kloet, Buwalda, Bouman and Bohus1996). At this moment, there is neither evidence that complex (developmental) mental disorders, like autism, schizophrenia, Parkinson's disease, depression, posttraumatic stress disorder (PTSD), or anorexia nervosa, are caused by “bad” bacteria or a “leaky gut,” nor that these often chronic mental disorders can be cured by “good” bacteria. Alternative explanations of positive short-term actions of probiotics on brain and animal behavior are possible. For example, probiotics may be helpful in the clearance of gram-negative bacteria, such as Escherichia coli (Timmerman et al. Reference Timmerman, Koning, Mulder, Rombouts and Beynen2004). These E. coli bacteria have lipopolysaccharides (LPS) in their outer membrane that can produce inflammation. It has been shown that this increased the number and biological activity of serotonin transporters (SERTs) expressed by neurons and astrocytes and thereby reduced extracellular serotonin concentrations in prefrontal cortex and nucleus accumbens (Korte-Bouws et al. Reference Korte-Bouws, van Heesch, Westphal, Ankersmit, van Oosten, Güntürkün and Korte2018). In addition, LPS-induced anhedonia (i.e., inability to feel pleasure) was abolished in SERT-knockout animals, suggesting that inflammation produces depressive-like symptoms via increased SERT activity (van Heesch et al. Reference van Heesch, Prins, Konsman, Westphal, Olivier, Kraneveld and Korte2013). We agree with Hooks et al. that in future MGB research appropriate positive and negative controls and adequate statistical power have to be included to allow for the identification of cause and effect relationships. In addition, the field of MGB research would greatly improve when more attempts are made to falsify the hypothesis (Popper Reference Popper and Popper1963) that probiotics are always good. Successful examples of this approach are shown in recent studies. In healthy volunteers, it was shown that probiotics could not successfully colonize the gastrointestinal (GI) tracts of all participants, but only succeeded to do so in some (Zmora et al. Reference Zmora, Zilberman-Schapira, Suez, Mor, Dori-Bachash, Bashiardes, Kotler, Zur, Regev-Lehavi, Brik, Federici, Cohen, Linevsky, Rothschild, Moor, Ben-Moshe, Harmelin, Itzkovitz, Maharshak, Shibolet, Shapiro, Pevsner-Fischer, Sharon, Halpern, Segal and Elinav2018). After a treatment with antibiotics, the same probiotics colonized the GI tracts of all test participants, but surprisingly, this colonization prevented the host's normal microbiome and gut gene expression profile from returning to its own original state for months afterward (Suez et al. Reference Suez, Zmora, Zilberman-Schapira, Mor, Dori-Bachash, Bashiardes, Zur, Regev-Lehavi, Ben-Zeev, Federici, Horn, Cohen, Moor, Zeevi, Korem, Kotler, Harmelin, Itzkovitz, Maharshak, Shibolet, Pevsner-Fischer, Shapiro, Sharon, Halpern, Segal and Elinav2018). However, when autologous fecal microbiome transplant (aFMT) was used (i.e., the host's own bacteria collected from before the use of antibiotics), the native gut microbiome returned to normal within days. Hence, probiotics are not a “one-fits-all” solution; a personalized approach is necessary. Furthermore, attention should be given to the role of the native gut microbiome, the disturbance of it at a young age, and the possible long-term consequences for health. The influence of prebiotics on the recovery of the native gut microbiome deserves further attention. The abovementioned findings clearly show why results obtained with probiotics in MGB animal research cannot always be directly translated into successful human applications. In summary, we fully agree with Hooks et al. that MGB research is a field full of promise, but, indeed, only when in the future putative causal relationships into the complex multipathway interactions between the microbiome and the gut-brain axis are investigated and a more critical approach is adopted.