Hooks et al. critique top-cited peer-reviewed scientific literature in which authors claim to confirm that intestinal microbiota robustly manipulate the brains, behaviors, and minds of infected humans and animals. Perhaps epitomized by science review and sensational news media accounts of so-called mind-controlling Toxoplasma (Mayer et al. Reference Mayer, Knight, Mazmanian, Cryan and Tillisch2014; Sampson & Mazmanian Reference Sampson and Mazmanian2015; Stilling et al. Reference Stilling, Dinan and Cryan2016), these reports and labels sometimes create disproportionate science and lay community excitement about the possible role played by the gut-brain axis in modifying host cognitive-emotional states, particularly eco-evolutionary explanations for neurodisease etiologies, symptoms, and prophylaxes/treatments (Liu Reference Liu2017; Mayer et al. Reference Mayer, Knight, Mazmanian, Cryan and Tillisch2014; Sampson & Mazmanian Reference Sampson and Mazmanian2015; Stilling et al. Reference Stilling, Dinan and Cryan2016). Hooks et al. disapprove of such trends and prescriptively warn against accepting popular experimental findings and interpretations of host-microbe symbiosis often justified with outdated, inconclusive, and/or unsound microbiome, neuroendocrine, behavioral, and statistical procedures. The authors’ scrutiny of microbiota-gut-brain research should be welcomed by scientist and journalist alike and might help establish guiding principles for improving empirical approaches, as well as primary- and secondary-source reporting practices. However, in preferentially selecting a limited, albeit manageable, number of highly cited microbiota-gut-brain studies, Hooks et al.’s own critical assessment ironically under-represents the scientific richness and excellence found across a broader cross section of published research, including investigations verifying that harbored gut microbiota significantly affect the nervous systems and goal-directed behaviors of coevolved host organisms (cf. Clark Reference Clark2013a; Reference Clark2013b; Reference Clark2018; Clark and Eisenstein Reference Clark and Eisenstein2013; Clark et al. Reference Clark, Eisenstein and Krahl2013). The authors’ inattention to that larger body of work, despite hopeful concluding statements about the basic and clinical science benefits of emerging microbiology research rigor, needlessly undermines their intent for fair accurate meta-analytical evaluation and meaningful fact-motivated advances within the field of inquiry.
To contrast and embellish Hooks et al.’s position based on 25 narrowly chosen literature examples, I enlist a small set of less cited peer-reviewed publications that typify capably performed and reported science demonstrating causal relationships between gut-brain-axis status and infected host health, development, behavior, and mind (cf. Erickson et al. Reference Erickson, Jesudhasan, Mayer, Narbad, Winter and Pfeiffer2018; Karst Reference Karst2016; Kuss et al. Reference Kuss, Best, Etheredge, Pruijssers, Frierson, Hooper, Dermody and Pfeiffer2011; Robinson & Pfeiffer Reference Robinson and Pfeiffer2014; Wilks & Golovkina Reference Wilks and Golovkina2012). These decade-spanning findings, proving neurotropic enteroviruses co-opt commensal gut microbiota during complex infection-cycle interactions, permit credible eco-evolutionary interpretations about infectivity, raising surprising doubt as to proper usage of “commensal” when defining benign symbiosis between various intestinal bacteria and host organisms. Through convergent evolution (e.g., zoonosis/zooanthroponosis) and/or coevolution pathways, certain neurotropic enteroviruses, such as RNA poliovirus, and their bacterial associates, such as nonpathogenic Escherichia coli, adapted a powerful biomimicry attack on human and animal hosts. Viruses, in such scenarios, increase their fitness by cryptically binding to bacteria-surface polysaccharides, a process termed “Trojan horse” or “raft” host incursion, to facilitate virus capsid/viron stabilization, host-immunodefense evasion, host-cell docking, and later (virus-virus) genetic recombination, replication, pathogenesis, and transmission. These cosmopolitan virus-microbe relations, ignored by Hooks et al. as legitimate mechanisms for gut-microbiota host manipulation, produce notable host central nervous system (CNS) disturbances at cellular and systems levels, including up-regulated cytokine and chemokine synthesis, apotosis and autophagy, neuroinflammation, and additional sequalae. Both immediate and delayed CNS disturbances may cause severe to fatal neurodevelopmental, neuromotor, and neuropsychiatric complications that further optimize virus fitness. Contrary to observed direct virus action, bacterial Trojan horses or rafts indirectly exert great harm over host health, development, behavior, and mind – prohibiting their classification as genuine commensal symbionts. Yet, the eco-evolutionary advantages of host-disease incidence, severity, timing, and duration remain poorly understood for the optimization of bacteria fitness and therefore continue to limit rational data interpretations.
Nevertheless, after reading Hooks et al.’s reproach of widespread unscholarly data interpretations in microbiota-gut-brain literature, one may expect bad reporting habits for the abovementioned model of intestinal bacteria activity, similar to misleading mind-control attributions for Toxoplasma infections. Many playful, flashy, even personifying interpretations and labels, now common to modern-day multimedia presentation styles, enrich the public's imagery of difficult-to-comprehend science concepts. For example, the catchphrase of “fair-weather-friend” colorfully connotes still largely unknown bacterial benefits of switching from commensal to pathogen-like host-microbe symbiosis strategies. Such language, as noted by Hooks et al., frequently exceeds boundaries of sound scientific convention, exchanging masterful science for masterful hyperbole. Evidence of this tendency seems almost absent for reports on enterovirus-hijacked commensal gut bacteria. Inexhaustive searches of primary and secondary science-reporting sources yield few marginal descriptions, including “foe-or-friend” gut microbiota (David Reference David2011), rightly challenging and qualifying eco-evolutionary notions of bacterial commensalism – a result that juxtaposes over-use of coined “viral understudy” and “friendly” to depict speculative host-promoting viral phenomena (e.g., Bordon Reference Bordon2015; Ray Reference Ray2015). The reasons underlying competent interpretation and label use likely originate with responsible primary-science methods and reporting, which, in turn, help deter subsequent mischaracterization of facts in secondary sources, procedures well advocated by Hooks et al. If true, the majority of lesser cited microbiota-gut-brain articles, as compared with top-cited ones, might better comply with Hooks et al.’s recommendations for elevating science methods and journalism standards. Only more thorough literature-inclusive meta-analyses, waiting to be conducted by Hooks et al. and/or alternative authors, may thus validate the actual full impact of rarely to highly cited publications on the microbiota-gut-brain research field and the content of its science review and trendy news media narratives.
Hooks et al. employ literature meta-analysis to identify flaws in microbiota-gut-brain research. They ably craft a taut message around their findings, which emphasize the catastrophic consequences and potential remedies of accepting inferior work into the official scientific record, including empirically unfounded eco-evolutionary interpretations and buzzwords. The authors show indisputable good judgment in their call to science and lay communities for stringent research and publishing regulation. However, if literature meta-analyses become a fundamental tool to achieve those goals, as I believe they should, then assumptions supporting that effort must be consistent and complete. Unfortunately, the authors, like many people, mistakenly over-value highly cited peer-reviewed publications as representative, if not quality, science and miss superior research falling below arbitrary thresholds of professional and/or amateur popularity. Although Hooks et al. present microbiota-gut-brain research problems worthy of notice, their choice in science articles might not correctly define the microbiota-gut-brain field of study. This lingering confusion further reinforces growing desires to also perfect meta-analytical science review publishing standards with impartial, statistically argued comprehensive findings.
Hooks et al. critique top-cited peer-reviewed scientific literature in which authors claim to confirm that intestinal microbiota robustly manipulate the brains, behaviors, and minds of infected humans and animals. Perhaps epitomized by science review and sensational news media accounts of so-called mind-controlling Toxoplasma (Mayer et al. Reference Mayer, Knight, Mazmanian, Cryan and Tillisch2014; Sampson & Mazmanian Reference Sampson and Mazmanian2015; Stilling et al. Reference Stilling, Dinan and Cryan2016), these reports and labels sometimes create disproportionate science and lay community excitement about the possible role played by the gut-brain axis in modifying host cognitive-emotional states, particularly eco-evolutionary explanations for neurodisease etiologies, symptoms, and prophylaxes/treatments (Liu Reference Liu2017; Mayer et al. Reference Mayer, Knight, Mazmanian, Cryan and Tillisch2014; Sampson & Mazmanian Reference Sampson and Mazmanian2015; Stilling et al. Reference Stilling, Dinan and Cryan2016). Hooks et al. disapprove of such trends and prescriptively warn against accepting popular experimental findings and interpretations of host-microbe symbiosis often justified with outdated, inconclusive, and/or unsound microbiome, neuroendocrine, behavioral, and statistical procedures. The authors’ scrutiny of microbiota-gut-brain research should be welcomed by scientist and journalist alike and might help establish guiding principles for improving empirical approaches, as well as primary- and secondary-source reporting practices. However, in preferentially selecting a limited, albeit manageable, number of highly cited microbiota-gut-brain studies, Hooks et al.’s own critical assessment ironically under-represents the scientific richness and excellence found across a broader cross section of published research, including investigations verifying that harbored gut microbiota significantly affect the nervous systems and goal-directed behaviors of coevolved host organisms (cf. Clark Reference Clark2013a; Reference Clark2013b; Reference Clark2018; Clark and Eisenstein Reference Clark and Eisenstein2013; Clark et al. Reference Clark, Eisenstein and Krahl2013). The authors’ inattention to that larger body of work, despite hopeful concluding statements about the basic and clinical science benefits of emerging microbiology research rigor, needlessly undermines their intent for fair accurate meta-analytical evaluation and meaningful fact-motivated advances within the field of inquiry.
To contrast and embellish Hooks et al.’s position based on 25 narrowly chosen literature examples, I enlist a small set of less cited peer-reviewed publications that typify capably performed and reported science demonstrating causal relationships between gut-brain-axis status and infected host health, development, behavior, and mind (cf. Erickson et al. Reference Erickson, Jesudhasan, Mayer, Narbad, Winter and Pfeiffer2018; Karst Reference Karst2016; Kuss et al. Reference Kuss, Best, Etheredge, Pruijssers, Frierson, Hooper, Dermody and Pfeiffer2011; Robinson & Pfeiffer Reference Robinson and Pfeiffer2014; Wilks & Golovkina Reference Wilks and Golovkina2012). These decade-spanning findings, proving neurotropic enteroviruses co-opt commensal gut microbiota during complex infection-cycle interactions, permit credible eco-evolutionary interpretations about infectivity, raising surprising doubt as to proper usage of “commensal” when defining benign symbiosis between various intestinal bacteria and host organisms. Through convergent evolution (e.g., zoonosis/zooanthroponosis) and/or coevolution pathways, certain neurotropic enteroviruses, such as RNA poliovirus, and their bacterial associates, such as nonpathogenic Escherichia coli, adapted a powerful biomimicry attack on human and animal hosts. Viruses, in such scenarios, increase their fitness by cryptically binding to bacteria-surface polysaccharides, a process termed “Trojan horse” or “raft” host incursion, to facilitate virus capsid/viron stabilization, host-immunodefense evasion, host-cell docking, and later (virus-virus) genetic recombination, replication, pathogenesis, and transmission. These cosmopolitan virus-microbe relations, ignored by Hooks et al. as legitimate mechanisms for gut-microbiota host manipulation, produce notable host central nervous system (CNS) disturbances at cellular and systems levels, including up-regulated cytokine and chemokine synthesis, apotosis and autophagy, neuroinflammation, and additional sequalae. Both immediate and delayed CNS disturbances may cause severe to fatal neurodevelopmental, neuromotor, and neuropsychiatric complications that further optimize virus fitness. Contrary to observed direct virus action, bacterial Trojan horses or rafts indirectly exert great harm over host health, development, behavior, and mind – prohibiting their classification as genuine commensal symbionts. Yet, the eco-evolutionary advantages of host-disease incidence, severity, timing, and duration remain poorly understood for the optimization of bacteria fitness and therefore continue to limit rational data interpretations.
Nevertheless, after reading Hooks et al.’s reproach of widespread unscholarly data interpretations in microbiota-gut-brain literature, one may expect bad reporting habits for the abovementioned model of intestinal bacteria activity, similar to misleading mind-control attributions for Toxoplasma infections. Many playful, flashy, even personifying interpretations and labels, now common to modern-day multimedia presentation styles, enrich the public's imagery of difficult-to-comprehend science concepts. For example, the catchphrase of “fair-weather-friend” colorfully connotes still largely unknown bacterial benefits of switching from commensal to pathogen-like host-microbe symbiosis strategies. Such language, as noted by Hooks et al., frequently exceeds boundaries of sound scientific convention, exchanging masterful science for masterful hyperbole. Evidence of this tendency seems almost absent for reports on enterovirus-hijacked commensal gut bacteria. Inexhaustive searches of primary and secondary science-reporting sources yield few marginal descriptions, including “foe-or-friend” gut microbiota (David Reference David2011), rightly challenging and qualifying eco-evolutionary notions of bacterial commensalism – a result that juxtaposes over-use of coined “viral understudy” and “friendly” to depict speculative host-promoting viral phenomena (e.g., Bordon Reference Bordon2015; Ray Reference Ray2015). The reasons underlying competent interpretation and label use likely originate with responsible primary-science methods and reporting, which, in turn, help deter subsequent mischaracterization of facts in secondary sources, procedures well advocated by Hooks et al. If true, the majority of lesser cited microbiota-gut-brain articles, as compared with top-cited ones, might better comply with Hooks et al.’s recommendations for elevating science methods and journalism standards. Only more thorough literature-inclusive meta-analyses, waiting to be conducted by Hooks et al. and/or alternative authors, may thus validate the actual full impact of rarely to highly cited publications on the microbiota-gut-brain research field and the content of its science review and trendy news media narratives.
Hooks et al. employ literature meta-analysis to identify flaws in microbiota-gut-brain research. They ably craft a taut message around their findings, which emphasize the catastrophic consequences and potential remedies of accepting inferior work into the official scientific record, including empirically unfounded eco-evolutionary interpretations and buzzwords. The authors show indisputable good judgment in their call to science and lay communities for stringent research and publishing regulation. However, if literature meta-analyses become a fundamental tool to achieve those goals, as I believe they should, then assumptions supporting that effort must be consistent and complete. Unfortunately, the authors, like many people, mistakenly over-value highly cited peer-reviewed publications as representative, if not quality, science and miss superior research falling below arbitrary thresholds of professional and/or amateur popularity. Although Hooks et al. present microbiota-gut-brain research problems worthy of notice, their choice in science articles might not correctly define the microbiota-gut-brain field of study. This lingering confusion further reinforces growing desires to also perfect meta-analytical science review publishing standards with impartial, statistically argued comprehensive findings.