How does microbiota research impact our understanding of biological individuality? We summarize the interdisciplinary summer school on "Microbiota, Symbiosis and Individuality: Conceptual and Philosophical Issues" (July 2019), which was supported by a European Research Council starting grant project "Immunity, DEvelopment, and the Microbiota" (IDEM). The summer school centered around interdisciplinary group work on four facets of microbiota research: holobionts, individuality, causation, and human health. The conceptual discussion of cutting-edge empirical research provided new insights into microbiota (...) and highlights the value of incorporating into meetings experts from other disciplines, such as philosophy and history of science. (shrink)

We propose the “microbiota‐inflammasome” hypothesis of major depressive disorder (MDD, a mental illness affecting the way a person feels and thinks, characterized by long‐lasting feelings of sadness). We hypothesize that pathological shifts in gut microbiota composition (dysbiosis) caused by stress and gut conditions result in the upregulation of pro‐inflammatory pathways mediated by the Nod‐like receptors family pyrin domain containing 3 (NLRP3) inflammasome (an intracellular platform involved in the activation of inflammatory processes). This upregulation exacerbates depressive symptomatology and further (...) compounds gut dysbiosis. In this review we describe MDD/chronic stress‐induced changes in: 1) NLRP3 inflammasome; 2) gut microbiota; and 3) metabolic pathways; and how inflammasome signaling may affect depressive‐like behavior and gut microbiota composition. The implication is that novel therapeutic strategies could emerge for MDD and co‐morbid conditions. A number of testable predictions surface from this microbiota‐gut‐inflammasome‐brain hypothesis of MDD, using approaches that modulate gut microbiota composition via inflammasome modulation, fecal microbiota transplantation, psychobiotics supplementation, or dietary change. (shrink)

Microbiota-gut-brain research is a fast-growing field of inquiry with important implications for how human brain function and behaviour are understood. Researchers manipulate gut microbes to reveal connections between intestinal microbiota and normal brain functions or pathological states. Many claims are made about causal relationships between gut microbiota and human behaviour. By uncovering these relationships, MGB research aims to offer new explanations of mental health and potential avenues of treatment. So far, limited evaluation has been made of MGB's (...) methods and its core experimental findings, many of which are extensively reiterated in copious reviews of the field. These factors, plus the self-help potential of MGB, have combined to encourage uncritical public uptake of MGB discoveries. Both social and professional media focus on the potential for dietary intervention in mental health, and causal relationships are assumed to be established. Our target article has two main aims. One is to examine critically the core practices and findings of experimental MGB research and to raise questions about them for brain and behavioural scientists who may not be familiar with the field. The other is to challenge the way in which MGB findings are presented. Our positive goal is to suggest how current problems and weaknesses may be addressed, in order for both scientific and public audiences to gain a clearer picture of MGB research and its strengths and limitations. (shrink)

The success of fecal microbiota transplantation as a treatment for Clostrioides difficile infection has stirred excitement about the potential for microbiota transplantation as a therapy for a wide range of diseases and conditions. In this article, we discuss vaginal microbiota transplantation as “the next frontier” in microbiota transplantation and identify the medical, regulatory, and ethical challenges related to this nascent field. We further discuss what we anticipate will be the first context for testing VMT in clinical (...) trials, prevention of the recurrence of a condition referred to as bacterial vaginosis. We also compare clinical aspects of VMT with FMT and comment on how VMT may be similar to or different from FMT in ways that may affect research design and regulatory decisions. (shrink)

Fecal microbiota transplantation has demonstrated efficacy and is increasingly being used in the treatment of patients with recurrent Clostridium difficile infection. Despite a lack of high-quality trials to provide more information on the long-term effects of FMT, there has been great enthusiasm about the potential for expanding its applications. However, FMT presents many serious ethical and social challenges that must be addressed as part of a successful regulatory policy response. In this article, we draw on a sample of the (...) scientific and bioethics literatures to examine clusters of ethical and social issues arising in five main areas: informed consent and the vulnerability of patients; determining what a “suitable healthy donor” is; safety and risk; commercialization and potential exploitation of vulnerable patients; and public health implications. We find that these issues are complex and worthy of careful consideration by health care professionals. Desperation of a patient should not be the basis for selecting treatment with FMT, and the patient's interests should always be of paramount concern. Authorities must prioritize development of appropriate and effective regulation of FMT to safeguard patients and donors, promote further research into safety and efficacy, and avoid abuse of the treatment. (shrink)

Resident microbiota do not just shape host immunity, they can also contribute to host protection against pathogens and infectious diseases. Previous reviews of the protective roles of the microbiota have focused exclusively on colonization resistance localized within a microenvironment. This review shows that the protection against pathogens also involves the mitigation of pathogenic impact without eliminating the pathogens (i.e., “disease tolerance”) and the containment of microorganisms to prevent pathogenic spread. Protective microorganisms can have an impact beyond their niche, (...) interfering with the entry, establishment, growth, and spread of pathogenic microorganisms. More fundamentally, we propose a series of conceptual clarifications in support of the idea of a “co-immunity,” where an organism is protected by both its own immune system and components of its microbiota. -/- . (shrink)

The microbiota-gut-brain field holds huge potential for understanding behavioral development and informing effective early interventions for psychological health. To realize this potential, factors that shape the MGB axis in infancy must be integrated into a systemic framework that considers salient behavioral outcomes. This is best accomplished applying network analyses in large prospective, longitudinal investigations in humans.

Hooks et al. note that microbiota-gut-brain research suffers from serious methodological flaws and interpretative issues. We suggest two corrective measures: first, taking more seriously the need of interdisciplinary work; second, interpreting some of the methodological issues as ordinary challenges of standardization, typical of emerging disciplines.

The unexpected roles of the microbiota in cancer challenge explanations of carcinogenesis that focus on tumor-intrinsic properties. Most tumors contain bacteria and viruses, and the host’s proximal and distal microbiota influence both cancer incidence and therapeutic responsiveness. Continuing the history of cancer–microbe research, these findings raise a key question: to what extent is the microbiota relevant for clinical oncology? We approach this by critically evaluating three issues: how the microbiota provides a predictive biomarker of cancer growth (...) and therapeutic responsiveness, the microbiota’s causal role(s) in cancer development, and how therapeutic manipulations of the microbiota improve patient outcomes in cancer. Clarifying the conceptual and empirical aspects of the cancer-associated microbiota can orient future research and guide its implementation in clinical oncology. (shrink)

Resident microorganisms, known as the microbiota, are essential for many physiological functions including protection against pathogens. Microbiota is indeed required for proper immune system development and function, and can also host-independently protect against infections. Thus, a co-constructed view of host protection involving both host and microbiota, named ’co-immunity,’ has been proposed, and the idea of an ’immunological holobiont’ has been suggested. Yet this view of co-immunity might be too limited, as experimental work has shown that the immune (...) system is involved in functions other than protection, essentially development and repair. Microbiota, through co-immunity, is thereby most likely involved in these functions, although strong evidence is currently lacking. Moreover, as our point of view is mainly host-centered, we may miss the implications of co-immunity at broader scales, including cellular and population levels. Intriguingly, co-immunity effects could be beneficial for one function and/or one level, while being detrimental for others. All these elements should be taken into consideration for microbiota manipulation, in order to avoid potentially harmful side effects. (shrink)

Does exploration of the gut microbiota–brain axis expand our understanding of what it means to be human? Recognition and conceptualization of a gut microbiota–brain axis challenges our study of the nervous system. Here, integrating gut microbiota–brain research into the metaorganism model is proposed. The metaorganism—an expanded, dynamic unit comprising the host and commensal organisms—asserts a radical blurring between man and microbe. The metaorganism nervous system interacts with the exterior world through microbial‐colored lenses. Ongoing studies have reported that (...) gut microbes contribute to brain function and pathologies, even shaping higher neurological functions. How will continued collaborative efforts (e.g., between neurobiology and microbiology), including partnerships with the arts (e.g., philosophy), contribute to the knowledge of microbe‐to‐mind interactions? While this is not a systemic review, this nascent field is briefly described, highlighting ongoing challenges and recommendations for emerging gut microbiota–brain research. Also see the video abstract here https://youtu.be/lP9gOW8StXg. (shrink)

Alterations in the gut microbiome have increasingly been implicated in driving obesity and its associated diseases, but underlying mechanisms remain poorly defined. Herein, in addition to reviewing the field, we hypothesize that a highly significant causative factor of such inflammatory disease‐associated microbiome alterations is a more aggressive microbiota that encroaches upon its host, with components having high potential to activate host pro‐inflammatory gene expression in a manner that drives metabolic disease. We further hypothesize that a range of societal changes, (...) including use of antibiotics and increasing consumption of food additives, have provoked such microbiota aggression and, consequently, may be contributing factors to the increased incidence of obesity and its associated diseases. (shrink)

Reciprocal interactions between the host circadian clock and the microbiota are evidenced by recent literature. Interestingly, dysregulation of either the circadian clock or microbiota is associated with common human pathologies such as obesity, type 2 diabetes, or neurological disorders. However, it is unclear to what extent a perturbation of pathways regulated by both the circadian clock and microbiota is involved in the development of these disorders. It is speculated that these perturbations are associated with impaired growth hormone (...) (GH) secretion and sexual development. The GH axis is a broadly neglected pathway and could be the main converging point for the interaction of both circadian clock and microbiota. Here, the links between the circadian clock and microbiota are reviewed. Finally, the effects of chronodisruption and dysbiosis on physiology and pathology are discussed and it is speculated whether a common deregulation of the GH pathway could mediates those effects. (shrink)

There is a broad consensus in nutritional-microbiota research that high-fat (HF) diets are harmful to human health, at least in part through their modulation of the gut microbiota. However, various studies also support the inherent flexibility of the human gut and our microbiota’s ability to adapt to a variety of food sources, suggesting a more nuanced picture. In this article, we first discuss some problems facing basic translational research and provide a different framework for thinking about diet (...) and gut health in terms of metabolic flexibility. We then offer evidence that well-formulated HF diets, such as ketogenic diets, may provide healthful alternative fuel sources for the human gut. We place this in the context of cancer research, where this concern over HF diets is also expressed, and consider various potential objections concerning the effects of lipopolysaccharides, trimethylamine-N-oxide, and secondary bile acids on human gut health. We end by providing some general suggestions for how to improve research and clinical practice with respect to the gut microbiota when considering the framework of metabolic flexibility. (shrink)

In their article “Ethical Issues in Fecal Microbiota Transplantation in Practice,” Ma and colleagues (2017) raise a number of questions related to the development of fecal microbiota transplants (F...

Multidrug resistant organisms are a public health threat that have reduced the effectiveness of many available antibiotics. Antimicrobial stewardship programs have been tasked with reducing antibiotic use and therefore the emergence of MDROs. While fecal microbiota transplant has been proposed as therapy to reduce patient colonization of MDROs, this will require additional evidence to support an expansion of the current clinical indication for FMT. This article discusses the evidence and ethics of the expanded utilization of FMT by ASPs for (...) reasons other than severe recurrent or refractory Clostridioides difficile infection. (shrink)

The last decade has seen an explosion of research on the gut microbiota—the trillions of microorganisms that colonize the human gut. It is now clear that interindividual diversity in microbiota composition plays an important role in determining susceptibility to a wide variety of diseases. However, identifying the precise changes in microbiota composition that play causal roles has remained a largely unrealized goal. Here, we propose that functional classifications of microbes based on their interactions with and effects on (...) the host—particularly the host immune system—will illuminate the role of the microbiota in shaping human physiology. We outline the benefits of “functional” classification compared to phylogenetic classifications, and review current efforts at functional classification of the microbiota. Finally, we outline a theoretical framework for classifying host-microbiota interactions. Future advances enabling broader functional classifications of the microbiota promise to revolutionize our understanding of the role of gut microbes in health and disease. Functional classifications of the human microbiota reveal previously hidden patterns and will be key to cracking the microbiota composition code. This figure shows a theoretical comparison between phylogenetic classification and functional classification of a host-associated microbial community. (shrink)

Dietary fiber and prebiotics consistently modulate microbiota composition and function and hence may constitute a powerful tool in microbiota-gut-brain axis research. However, this is largely ignored in Hooks et al.’s analysis, which highlights the limitations of probiotics in establishing microbiome-mediated effects on neurobehavioral functioning and neglects discussing the potential of prebiotics in warranting the microbiota's role in such effects.

Fecal microbiota transplantation is reportedly the most effective therapy for relapsing Clostridium Difficile infection and a potential therapeutic option for many diseases. It also poses important ethical concerns. This study is an attempt to assess clinicians’ perception and attitudes towards ethical and social challenges raised by fecal microbiota transplantation. A questionnaire was developed which consisted of 20 items: four items covered general aspects, nine were about ethical aspects such as informed consent and privacy issues, four concerned social and (...) regulatory issues, and three were about an FMT bank. This was distributed to participants at the Second China gastroenterology and FMT conference in May 2015. Basic descriptive statistical analyses and simple comparative statistical tests were performed. Nearly three quarters of the 100 respondents were gastro-enterologist physicians. 89% of all respondents believed FMT is a promising treatment modality for some diseases and 88% of whom chose clinical efficacy as the primary reason for recommending FMT. High expectation from patients and pressure on clinicians was reported as the most frequent reasons for not recommending FMT. The clinicians who had less familiarity with FMT reported significantly more worry related to the dignity and psychological impact of FMT compared to those who have high familiarity with FMT.More than half of the respondents were concerned about the commercialization of FMT, although almost one in five respondents did not see this as a problem. We found most respondents have positive attitudes towards FMT but low awareness of published evidence. Informed consent for vulnerable patients, privacy and protection of donors were perceived as the most challenging ethical aspects of FMT. This study identified areas of limited knowledge and ways of addressing ethical issues and indicates the need to devise the education and training for clinicians on FMT. (shrink)

Microbes in the gastrointestinal tract are under selective pressure to manipulate host eating behavior to increase their fitness, sometimes at the expense of host fitness. Microbes may do this through two potential strategies: (i) generating cravings for foods that they specialize on or foods that suppress their competitors, or (ii) inducing dysphoria until we eat foods that enhance their fitness. We review several potential mechanisms for microbial control over eating behavior including microbial influence on reward and satiety pathways, production of (...) toxins that alter mood, changes to receptors including taste receptors, and hijacking of the vagus nerve, the neural axis between the gut and the brain. We also review the evidence for alternative explanations for cravings and unhealthy eating behavior. Because microbiota are easily manipulatable by prebiotics, probiotics, antibiotics, fecal transplants, and dietary changes, altering our microbiota offers a tractable approach to otherwise intractable problems of obesity and unhealthy eating. (shrink)

To enable microbial colonisation of the gut mucosa, the intestinal immune system must not only react to danger signals but also recognize cues that indicate safety. Safety recognition, paradoxically, is mediated by the same environmental sensors that are involved in signalling danger. Indeed, in addition to their well established role in inducing inflammation in response to stress signals, pattern recognition receptors (PRRs) and a variety of metabolic sensors also promote gut-microbiota symbiosis by responding to "microbial symbiosis factors", "resolution-associated molecular (...) patterns", markers of energy extraction and other signals indicating the absence of pathogenic infection and tissue damage. Here we focus on how the paradoxical role of immune receptors and other environmental sensors define the microbiota signature of the individual. (shrink)

This comment expands on Hooks et al.’s criticism of the problematic and overly general uses of “stress” within the microbiota-gut-brain field. The comment concludes that, for the microbiota-gut-brain field, much work is yet to be done in terms of how we explore and understand biology vis-à-vis psychology.

In this article, the authors explore the impact of a potential future regulatory decision by FDA whether or not to continue its enforcement discretion policy allowing physicians to perform, and stool banks to sell, stool product for fecal microbiota transplantation as a treatment for recurrent Clostridium Difficile infection without an Investigative New Drug application. The paper looks at the Agency's regulatory options in light of the current gut microbiota based products that are in the FDA pipeline for drug (...) approval and the potential impact and repercussions of their approval on FDA action. In laying out FDA's options we consider the implications of market exclusivity and off-label use of newly approved drugs. Ultimately, we explore the potential impact of FDA's decision on patients, research, and innovation. (shrink)

According to a shared functionalist view in philosophy of mind, a cognitive system, and cognitive function thereof, is based on the components of the organism it is realized by which, indeed, play a causal role in regulating our cognitive processes. This led philosophers to suggest also that, thus, cognition could be seen as an extended process, whose vehicle can extend not only outside the brain but also beyond bodily boundaries, on different kinds of devices. This is what we call the (...) ‘Externally Extended Cognition Thesis.’ This notion has generated a lively debate. Here, we offer a novel notion of extended cognition, according to which cognition can be seen as being realized outside the brain, but still inside the body. This is what we call the ‘Internally Extended Cognition Thesis’. Not only our thesis but also our approach while defending it is innovative. The argument we offer is supported by recent empirical findings in the life sciences and biomedicine, which suggest that the gut microbiota’s activity has a functional role in regulating our cognitive processes and behaviors. In doing so, we embrace the holobiont-perspective, according to which it is possible to claim that what we call biological individuals are not autonomous entities with clear boundaries, but should rather be seen as networks of multiple interactions among species. Thus, by analyzing different sets of evidence in light of the holobiont-perspective, we argue that the gut microbiota could be seen as a component of our organism. On the basis of the philosophical interpretation of this evidence, however, we also suggest that there are no impediments standing the way of considering the gut microbiota also as a functional extension of our cognitive system. If so, this amounts to extending cognition out of ‘our skull’, though still confining it within ‘our body’: to ‘our gut’. This is an instance of the ‘Internally Extended Cognition Thesis,’ whose benefits for an original theory of extended cognition are discussed. (shrink)

The gut microbiota is an important component of the human body and its immune‐modulating and metabolic activities are critical to maintain good health. Gut microbes, however, are sensitive to changes in diet, exposure to antibiotics, or infections, all of which cause transient disruptions in the microbial composition, a phenomenon known as dysbiosis. It is now recognized that microbial dysbiosis is at the root of many gastrointestinal disorders. However, the mechanisms through which bacterial dysbiosis initiates disease are not fully understood. (...) Microbially‐derived metabolites and their role in disease have also attracted significant attention. Identification of cancer‐associated bacteria and understanding the contributions of microbial metabolism in health and disease are exciting but challenging areas that will allow defining microbial biomarkers for predicting gastrointestinal disorders. Understanding the complex interactions between gut microbiota, diet, host immune system and host genetics will be critical to developing more personalized therapies and approaches to treat disease. (shrink)

The microbiota-gut-brain axis field is at an exciting stage, but the most recent developments in microbiota research still have to find their way into MGB studies. Here we outline the standards for microbiome data generation, the appropriate statistical techniques, and the covariates that should be included in MGB studies to optimize discovery and translation to clinical applications.

We argue for the importance of looking at the microbiota-gut-brain axis from a human developmental perspective. For this purpose, we first briefly highlight emerging research with infants attesting that the microbiome plays a role in early brain and cognitive development. We then discuss the use of developmentally informed humanized mouse models and implications of microbiome research that go beyond probiotic administration.

Regulatory agencies vary widely in their classification of FMT, with significant impact on patient access. This article conducts a global survey of national regulations and collates existing FMT classification statuses, ultimately suggesting that the human cell and tissue product designation best fits FMT's characteristics and that definitional objectives to that classification may be overcome.

Background Fecal microbiota transplant (FMT) is a treatment modality that involves the introduction of stool from a healthy pre-screened donor into the gastrointestinal tract of a patient. It exerts its therapeutic effects by remodeling the gut microbiota and treating microbial dysbiosis-imbalance. FMT is not regulated in Jordan, and regulatory effort for FMT therapy in Jordan, an Islamic conservative country, might be faced with unique cultural, social, religious, and ethical challenges. We aimed to assess knowledge, attitudes, and perceptions of (...) ethical and social issues of FMT use among Jordanian healthcare professionals. Methods An observational, cross-sectional study design was used to assess knowledge, attitudes, and perceptions of ethical and social issues of FMT among 300 Jordanian healthcare professionals. Results A large proportion (39 %) thought that the safety and efficacy of this technique are limited and 29.3 % thought there is no evidence to support its use. Almost all (95 %) responded that they would only perform it in certain cases, if ethically justified, and 48.3 % would use it due to treatment failure of other approaches. When reporting about reasons for not using it, 40 % reported that they would not perform it due to concerns about medical litigation, fear of infections (38 %), and lack of knowledge of long safety and efficacy (31.3 %). Interestingly, all practitioners said they would perform this procedure through the lower rather than upper gastrointestinal tract modality and the majority will protect the patient’s confidentiality via double-blinding (43.3 %). For a subset of participants (n = 100), the cultural constraints that might affect the choice of performing FMT were mainly due to donor’s religion, followed by dietary intake, and alcohol consumption. Conclusions Our healthcare practitioners are generally reluctant to use the FMT modality due to religious and ethical reasons but would consider it if there was a failure of other treatment and after taking into consideration many legislative, social, ethical and practice-based challenges including safety, efficacy and absence of guidelines. (shrink)

For gut microbiota to influence behavior, microorganisms should be able to interfere with specific brain neurochemical circuitries. Understanding these molecular mechanisms is a key task in the new microbiota-gut-brain field. Recent studies have revealed that one major mechanistic link is the modulation of neuropeptide signaling by homologous bacterial proteins acting both directly and indirectly via production of neuropeptide-reactive immunoglobulins.

Our analysis of microbiota-gut-brain research took MGB to task for some of its methods, concepts, and interpretations. Commentators then raised numerous issues about the neuroscientific and microbiome aspects of MGB and how it can be understood as a field. We respond by addressing the dimensionality and causal focus of MGB.

Coordination of immune responses in the gut is a complex task. In order to fight pathogens and maintain a defined population of commensal microbes, the mucosal immune system has to coordinate information from the external (luminal) and internal (abluminal) environment and respond accordingly. Dendritic cells (DCs) are crucial cell types involved in this process as they integrate these signals and direct immunogenic or tolerogenic responses. Here, we review how various functions of DCs depend on microbial stimuli and how these stimuli (...) influence the course of immune activation. (shrink)

The human intestinal ecosystem, previously called the gut microflora is now known as the Human Gut Microbiota. Microbiome research has emphasized the potential role of this ecosystem in human homeostasis, offering unexpected opportunities in therapeutics, far beyond digestive diseases. It has also highlighted ethical, social and commercial concerns related to the gut microbiota. As diet factors are accepted to be the major regulator of the gut microbiota, the modulation of its composition, either by antibiotics or by food (...) intake, should be regarded as a fascinating tool for improving the human health. Scientists, the food industry, consumers and policymakers alike are involved in this new field of nutrition. Defining how knowledge about the HGM is being translated into public perception has never been addressed before. This raises the question of metaphors associated with the HGM, and how they could be used to improve public understanding, and to influence individual decision-making on healthcare policy. This article suggests that a meeting of stakeholders from the social sciences, basic research and the food industry, taking an epistemological approach to the HGM, is needed to foster close, innovative partnerships that will help shape public perception and enable novel behavioural interventions that would benefit public health. (shrink)

In this commentary, we point to guidelines for performing human neuroimaging studies and their reporting in microbiota-gut-brain articles. Moreover, we provide a view on interpretational issues in MGB studies, with a specific focus on gut microbiota–derived metabolites. Thus, extending the target article, we provide recommendations to the field to increase reproducibility and relevance of this type of MGB study.

The amygdala is a key brain area regulating responses to stress and emotional stimuli, so improving our understanding of how it is regulated could offer novel strategies for treating disturbances in emotion regulation. As we review here, a growing body of evidence indicates that the gut microbiota may contribute to a range of amygdala-dependent brain functions from pain sensitivity to social behavior, emotion regulation, and therefore, psychiatric health. In addition, it appears that the microbiota is necessary for normal (...) development of the amygdala at both the structural and functional levels. While further investigations are needed to elucidate the exact mechanisms of microbiota-to-amygdala communication, ultimately, this work raises the intriguing possibility that the gut microbiota may become a viable treatment target in disorders associated with amygdala dysregulation, including visceral pain, post-traumatic stress disorder, and beyond. Also see the video abstract here: https://youtu.be/O5gvxVJjX18 The amygdala plays a central role in regulating many aspects of behavior in rodents and humans, from pain responding to social interaction and psychiatric function. Accumulating evidence suggests microbiota-to-amygdala communication along the gut-brain axis is a key modulator of these amygdala-dependent behaviors, with critical implications for health and disease. (shrink)

Here we argue that a multidisciplinary research approach, such as currently practised in the field of developmental cognitive neuroscience, is key to maintaining current momentum and to future-proof the field of microbiome-gut-brain research. Moreover, such a comprehensive approach will also bring us closer to our aims of translation and targeted intervention approaches to improve mental health and well-being.

Hooks et al. posit that gastrointestinal microbes alter the end state of development indirectly. Here, we present the immune system as the link that facilitates communication between the gut and the brain. Illustrating the case of autism spectrum disorder, we explicate the role of the immune system in responding to microbial dysbiosis by inducing an inflammatory state that affects neurodevelopment. We propose two models: directly, within the infant, and indirectly, via maternal and infant systems.

Some neurotropic enteroviruses hijack Trojan horse/raft commensal gut bacteria to render devastating biomimicking cryptic attacks on human/animal hosts. Such virus-microbe interactions manipulate hosts’ gut-brain axes with accompanying infection-cycle-optimizing central nervous system disturbances, including severe neurodevelopmental, neuromotor, and neuropsychiatric conditions. Co-opted bacteria thus indirectly influence host health, development, behavior, and mind as possible “fair-weather-friend” symbionts, switching from commensal to context-dependent pathogen-like strategies benefiting gut-bacteria fitness.

While largely studied because of their harmful effects on human health, there is growing appreciation that bacteria are important partners for invertebrates and vertebrates, including man. Epithelia in metazoans do not only select their microbiota; a coevolved consortium of microbes enables both invertebrates and vertebrates to expand the range of diet supply, to shape the complex immune system and to control pathogenic bacteria. Microbes in zebrafish and mice regulate gut epithelial homeostasis. In a squid, microbes control the development of (...) the symbiotic light organ. These discoveries point to a key role for bacteria in any metazoan existence, and imply that beneficial bacteria‐host interactions should be considered an integral part of development and evolution. (shrink)

In humans, the intestine is the major reservoir of microbes. Although the intestinal microbial community exists in a state of homeostasis called eubiosis, environmental and genetics factors can lead to microbial perturbation or dysbiosis, a state associated with various pathologies including inflammatory bowel diseases (IBD) and colorectal cancer (CRC). Dysbiotic microbiota is thought to contribute to the initiation and progression of CRC. At the opposite end of the spectrum, two recently published studies in Science reveal that the microbiota (...) is essential for chemotherapeutic drug efficacy, suggesting a beneficial microbial function in cancer management. The dichotomy between the beneficial and detrimental roles of the microbiota during cancer initiation, progression, and treatment emphasize the interwoven relationship between bacteria and cancer. Moreover, these findings suggest that the microbiota could be considered as a therapeutic target, not only at the level of cancer prevention, but also during management, i.e. by enhancing the efficacy of chemotherapeutics. (shrink)

Large‐scale characterization of the human microbiota has largely focused on Western adults, yet these populations may be uncharacteristic because of their diets and lifestyles. In particular, the rise of “Western diseases” may in part stem from reduced exposure to, or even loss of, microbes with which humans have coevolved. Here, we review beneficial microbes associated with pathogen resistance, highlighting the emerging role of complex microbial communities in protecting against disease. We discuss ways in which modern lifestyles and practices may (...) deplete physiologically important microbiota, and explore prospects for reintroducing or encouraging the growth of beneficial microbes to promote the restoration of healthy microbial ecosystems. (shrink)

As crucial interface organs gut and skin have much in common. Therefore it is unsurprising that several gut pathologies have skin co‐morbidities. Nevertheless, the reason for this remains ill explored, and neither mainstream gastroenterology nor dermatology research have systematically investigated the ‘gut‐skin axis'. Here, in reviewing the field, we propose several mechanistic levels on which gut and skin may interact under physiological and pathological circumstances. We focus on the gut microbiota, with its huge metabolic capacity, and the role of (...) dietary components as potential principle actors along the gut‐skin axis. We suggest that metabolites from either the diet or the microbiota are skin accessible. After defining open key questions around the nature of these metabolites, how they are sensed, and which cutaneous changes they can induce, we propose that understanding of these pathways will lead to novel therapeutic strategies based on targeting one organ to improve the health of the other. (shrink)

A new study entitled “Normal gut microbiota modulates brain development and behavior”, published in the Proceedings of the National Academy of Sciences, requires that we reconsider the notion that the brain is an immune‐privileged site. The authors demonstrate that intestinal microbiota must be present within a set time‐frame for normal synaptogenesis to occur in the brain. In the absence of intestinal microbiota, histopathological and behavioral abnormalities arise. These observations necessitate a new look at the many interconnections of (...) the immune system and the brain, suggesting new frontiers for research and new therapeutic strategies for neurodevelopmental diseases. (shrink)