The human microbiome–the microorganisms (bacteria, viruses, and fungi) that live within or around the human body. Damage or changes or abberations of this “microbial organ” may affect human health and lead to disease. Increasingly, the microbiome is seen as a key part in the initiation, regulation, and termination of all immune responses in the human body.
Quick bibliography: Articles–classic and recent–on the human microbiome and its effects on disease and behavior.
**updated April 2022**
*Alcock, J., Maley, C. C., & Aktipis, C. A. (2014). Is eating behavior manipulated by the gastrointestinal microbiota? evolutionary pressures and potential mechanisms. BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology, 36(10), 940-949. [PDF] [Cited by]
“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.”
*Borre, Y. E., Moloney, R. D., Clarke, G., Dinan, T. G., & Cryan, J. F. (2014). The impact of microbiota on brain and behavior: Mechanisms & therapeutic potential. Advances in Experimental Medicine and Biology, 817, 373-403. [Cited by]
“There is increasing evidence that host-microbe interactions play a key role in maintaining homeostasis. Alterations in gut microbial composition is associated with marked changes in behaviors relevant to mood, pain and cognition, establishing the critical importance of the bi-directional pathway of communication between the microbiota and the brain in health and disease. Dysfunction of the microbiome-brain-gut axis has been implicated in stress-related disorders such as depression, anxiety and irritable bowel syndrome and neurodevelopmental disorders such as autism. Bacterial colonization of the gut is central to postnatal development and maturation of key systems that have the capacity to influence central nervous system (CNS) programming and signaling, including the immune and endocrine systems. Moreover, there is now expanding evidence for the view that enteric microbiota plays a role in early programming and later response to acute and chronic stress. This view is supported by studies in germ-free mice and in animals exposed to pathogenic bacterial infections, probiotic agents or antibiotics. Thus, the concept of a microbiome-brain-gut axis is emerging, suggesting microbiota-modulating strategies may be a tractable therapeutic approach for developing novel treatments for CNS disorders.”
*Ege, M. J., Mayer, M., Normand, A., Genuneit, J., Cookson, W. O. C. M., Braun-Fahrländer, C., . . . GABRIELA Transregio 22, S. G. (2011). Exposure to environmental microorganisms and childhood asthma. The New England Journal of Medicine, 364(8), 701-709. [PDF] [Cited by]
“Children who grow up in environments that afford them a wide range of microbial exposures, such as traditional farms, are protected from childhood asthma and atopy. In previous studies, markers of microbial exposure have been inversely related to these conditions. In two cross-sectional studies, we compared children living on farms with those in a reference group with respect to the prevalence of asthma and atopy and to the diversity of microbial exposure. In both studies, children who lived on farms had lower prevalences of asthma and atopy and were exposed to a greater variety of environmental microorganisms than the children in the reference group.”
*Frame, L. A., Costa, E., & Jackson, S. A. (2020). Current explorations of nutrition and the gut microbiome: A comprehensive evaluation of the review literature. Nutrition Reviews, 78(10), 798-812. [PDF] [Cited by]
“The ability to measure the gut microbiome led to a surge in understanding and knowledge of its role in health and disease. The diet is a source of fuel for and influencer of composition of the microbiome.”
The review assessed “the understanding of the interactions between nutrition and the gut microbiome in healthy adults.” Searches were conducted in March and August 2018 in PubMed and Google Scholar and “were limited to the following: English, 2010–2018, healthy adults, and reviews. A total of 86 articles were independently screened for duplicates and relevance, based on preidentified inclusion criteria.”
Analysis: “research has focused on dietary fiber – microbiota fuel. The benefits of fiber center on short-chain fatty acids, which are required by colonocytes, improve absorption, and reduce intestinal transit time. Contrastingly, protein promotes microbial protein metabolism and potentially harmful by-products that can stagnate in the gut. The microbiota utilize and produce micronutrients; the bidirectional relationship between micronutrition and the gut microbiome is emerging. Nutrition has profound effects on microbial composition, in turn affecting wide-ranging metabolic, hormonal, and neurological processes. There is no consensus on what defines a “healthy” gut microbiome. Future research must consider individual responses to diet.”
*Gacesa, R., Kurilshikov, A., Vich Vila, A. et al. (2022). Environmental factors shaping the gut microbiome in a Dutch population. Nature. **new**
“Alterations in gut microbiota composition and function are associated with a broad range of human health disorders, including gastrointestinal and metabolic diseases and mental disorders.
The gut microbiome is associated with diverse diseases, but a universal signature of a healthy or unhealthy microbiome has not been identified, and there is a need to understand how genetics, exposome, lifestyle and diet shape the microbiome in health and disease. Here we profiled bacterial composition, function, antibiotic resistance and virulence factors in the gut microbiomes of 8,208 Dutch individuals from a three-generational cohort comprising 2,756 families. We correlated these to 241 host and environmental factors, including physical and mental health, use of medication, diet, socioeconomic factors and childhood and current exposome. We identify that the microbiome is shaped primarily by the environment and cohabitation. Only around 6.6% of taxa are heritable, whereas the variance of around 48.6% of taxa is significantly explained by cohabitation. By identifying 2,856 associations between the microbiome and health, we find that seemingly unrelated diseases share a common microbiome signature that is independent of comorbidities. Furthermore, we identify 7,519 associations between microbiome features and diet, socioeconomics and early life and current exposome, with numerous early-life and current factors being significantly associated with microbiome function and composition.
–Linking healthy and unhealthy microbiome patterns to childhood and current exposome, diet and socioeconomics, we observed that healthier diet, childhood and current exposures to rural environment and pets, exposure to green space and higher income share signals with healthy microbiome patterns
—Adult exposures also contribute to healthy or unhealthy microbiome patterns and that the environment shapes the microbiome throughout life, meaning that microbiome-targeted therapies could be effective throughout an individual’s life.
–Smoking, a high-carbohydrate diet and exposure to NO2 and small particulate matter (PM2.5) are positively correlated with disease-linked Clostridia and Ruminococcus species
–Air pollutants negatively affect the human gut microbiota and might increase the risk of gastrointestinal diseases
–Childhood exposures to smoking, pets and rural environment are associated with the adult microbiome
–Environmental exposures can have a long-lasting effect and that the microbiome reflects an individual’s history of exposures
Overall, this study provides a comprehensive overview of gut microbiome and the underlying impact of heritability and exposures that will facilitate future development of microbiome-targeted therapies.”
*Gohir, W., Ratcliffe, E. M., & Sloboda, D. M. (2015). Of the bugs that shape us: Maternal obesity, the gut microbiome, and long-term disease risk. Pediatric Research, 77(1-2), 196-204. [Cited by]
“Chronic disease risk is inextricably linked to our early-life environment, where maternal, fetal, and childhood factors predict disease risk later in life. Currently, maternal obesity is a key predictor of childhood obesity and metabolic complications in adulthood. Although the mechanisms are unclear, new and emerging evidence points to our microbiome, where the bacterial composition of the gut modulates the weight gain and altered metabolism that drives obesity. Over the course of pregnancy, maternal bacterial load increases, and gut bacterial diversity changes and is influenced by pre-pregnancy- and pregnancy-related obesity. Alterations in the bacterial composition of the mother have been shown to affect the development and function of the gastrointestinal tract of her offspring. How these microbial shifts influence the maternal–fetal–infant relationship is a topic of hot debate. This paper will review the evidence linking nutrition, maternal obesity, the maternal gut microbiome, and fetal gut development, bringing together clinical observations in humans and experimental data from targeted animal models.
“Growing evidence indicates that the mammalian microbiome can affect behaviour, and several symbionts even produce neurotransmitters. One common explanation for these observations is that symbionts have evolved to manipulate host behaviour for their benefit. Here, we evaluate the manipulation hypothesis by applying evolutionary theory to recent work on the gut–brain axis. Although the theory predicts manipulation by symbionts under certain conditions, these appear rarely satisfied by the genetically diverse communities of the mammalian microbiome. Specifically, any symbiont investing its resources to manipulate host behaviour is expected to be outcompeted within the microbiome by strains that do not manipulate and redirect their resources into growth and survival. Moreover, current data provide no clear evidence for manipulation. Instead, we show how behavioural effects can readily arise as a by-product of natural selection on microorganisms to grow within the host and natural selection on hosts to depend upon their symbionts. We argue that understanding why the microbiome influences behaviour requires a focus on microbial ecology and local effects within the host.
*Plunkett, C. H., & Nagler, C. R. (2017). The influence of the microbiome on allergic sensitization to food. Journal of Immunology, 198(2), 581-589. [PDF] [Cited by]
“The alarming increase in the incidence and severity of food allergies has coincided with lifestyle changes in Western societies, such as dietary modifications and increased antibiotic use. These demographic shifts have profoundly altered the coevolved relationship between host and microbiota, depleting bacterial populations critical for the maintenance of mucosal homeostasis. There is increasing evidence that the dysbiosis associated with sensitization to food fails to stimulate protective tolerogenic pathways, leading to the development of the type 2 immune responses that characterize allergic disease. Defining the role of beneficial allergy-protective members of the microbiota in the regulation of tolerance to food has exciting potential for new interventions to treat dietary allergies by modulation of the microbiota.
*Romano-Keeler, J., & Weitkamp, J. (2015). Maternal influences on fetal microbial colonization and immune development. Pediatric Research, 77(1-2), 189-195. [PDF] [Cited by]
“While critical for normal development, the exact timing of establishment of the intestinal microbiome is unknown. For example, although preterm labor and birth have been associated with bacterial colonization of the amniotic cavity and fetal membranes for many years, the prevailing dogma of a sterile intrauterine environment during normal term pregnancies has been challenged more recently. While found to be a key contributor of evolution in the animal kingdom, maternal transmission of commensal bacteria may also constitute a critical process during healthy pregnancies in humans with yet unclear developmental importance. Metagenomic sequencing has elucidated a rich placental microbiome in normal term pregnancies likely providing important metabolic and immune contributions to the growing fetus. Conversely, an altered microbial composition during pregnancy may produce aberrant metabolites impairing fetal brain development and life-long neurological outcomes. Here we review the current understanding of microbial colonization at the feto-maternal interface and explain how normal gut colonization drives a balanced neonatal mucosal immune system, while dysbiosis contributes to aberrant immune function early in life and beyond. We discuss how maternal genetics, diet, medications, and probiotics inform the fetal microbiome in preparation for perinatal and postnatal bacterial colonization.
*Ruokolainen, L., von Hertzen, L., Fyhrquist, N., Laatikainen, T., Lehtomäki, J., Auvinen, P., . . . Hanski, I. (2015). Green areas around homes reduce atopic sensitization in children. Allergy, 70(2), 195-202. [PDF] [Cited by]
“Western lifestyle is associated with high prevalence of allergy, asthma and other chronic inflammatory disorders. To explain this association, we tested the ‘biodiversity hypothesis’, which posits that reduced contact of children with environmental biodiversity, including environmental microbiota in natural habitats, has adverse consequences on the assembly of human commensal microbiota and its contribution to immune tolerance. The cover of forest and agricultural land within 2–5 km from the home was inversely and significantly associated with atopic sensitization. This relationship was observed for children 6 years of age and older.” The amount of green environment (forest and agricultural land) around homes was associated with fewer allergies in children. “The results indicate that early‐life exposure to green environments is especially important.”
*Thomas, R. M., & Jobin, C. (2020). Microbiota in pancreatic health and disease: The next frontier in microbiome research. Nature Reviews.Gastroenterology & Hepatology, 17(1), 53-64. [PDF] [Cited by]
“Diseases intrinsic to the pancreas such as pancreatitis, pancreatic cancer and type 1 diabetes mellitus impart substantial health and financial burdens on society but identification of novel mechanisms contributing to these pathologies are slow to emerge. A novel area of research suggests that pancreatic-specific disorders might be modulated by the gut microbiota, either through a local (direct pancreatic influence) or in a remote (nonpancreatic) fashion. In this Perspectives, we examine literature implicating microorganisms in diseases of the pancreas, specifically pancreatitis, type 1 diabetes mellitus and pancreatic ductal adenocarcinoma. We also discuss evidence of an inherent pancreatic microbiota and the influence of the intestinal microbiota as it relates to disease association and development.”
*Tilg, H., Zmora, N., Adolph, T. E., & Elinav, E. (2020). The intestinal microbiota fuelling metabolic inflammation. Nature Reviews. Immunology, 20(1), 40-54. [PDF] [Cited by] **New**
“Low-grade inflammation is the hallmark of metabolic disorders such as obesity, type 2 diabetes and nonalcoholic fatty liver disease. Emerging evidence indicates that these disorders are characterized by alterations in the intestinal microbiota composition and its metabolites, which translocate from the gut across a disrupted intestinal barrier to affect various metabolic organs, such as the liver and adipose tissue, thereby contributing to metabolic inflammation. Here, we discuss some of the recently identified mechanisms that showcase the role of the intestinal microbiota and barrier dysfunction in metabolic inflammation.”
For additional research on the microbiome, please see Science Primary Literature (database).
Questions? Please let me know ([email protected]).