щлThis is the first in a series of interviews highlighting the work of experts in the field of complex systems science. Dr. Ben Althouse, an Omidyar Fellow at the Santa Fe Institute, is a mathematical epidemiologist focusing on the dynamics of infectious disease transmission. Ben holds both an ScM in Biostatistics and a PhD in Epidemiology from the Johns Hopkins Bloomberg School of Public Health where he focused on understanding Dengue fever and other sylvatic mosquito-borne viruses (arboviruses) in Senegal using mechanistic modeling and the SIR model. Dr. Althouse also attended the Santa Fe Institute’s Complex Systems Summer School during his graduate studies.
Intestinal microbial communities have profound effects on host physiology. Whereas the symbiotic contribution of commensal bacteria is well established, the role of eukaryotic viruses that are present in the gastrointestinal tract under homeostatic conditions is undefined. Here we demonstrate that a common enteric RNA virus can replace the beneficial function of commensal bacteria in the intestine. Murine norovirus (MNV) infection of germ-free or antibiotic-treated mice restored intestinal morphology and lymphocyte function without inducing overt inflammation and disease. The presence of MNV also suppressed an expansion of group 2 innate lymphoid cells observed in the absence of bacteria, and induced transcriptional changes in the intestine associated with immune development and type I interferon (IFN) signalling. Consistent with this observation, the IFN-[agr] receptor was essential for the ability of MNV to compensate for bacterial depletion. Importantly, MNV infection offset the deleterious effect of treatment with antibiotics in models of intestinal injury and pathogenic bacterial infection. These data indicate that eukaryotic viruses have the capacity to support intestinal homeostasis and shape mucosal immunity, similarly to commensal bacteria.
IN the late 17th century, the Dutch naturalist Anton van Leeuwenhoek looked at his own dental plaque through a microscope and saw a world of tiny cells “very prettily a-moving.” He could not have predicted that a few centuries later, the trillions of microbes that share our lives — collectively known as the microbiome — would rank among the hottest areas of biology.
These microscopic partners help us by digesting our food, training our immune systems and crowding out other harmful microbes that could cause disease. In return, everything from the food we eat to the medicines we take can shape our microbial communities — with important implications for our health. Studies have found that changes in our microbiome accompany medical problems from obesity to diabetes to colon cancer.
Immediately following birth, the gastrointestinal tract is colonized with a complex community of bacteria, which helps shape the immune system. Under conditions of health, the immune system is able to differentiate between innocuous antigens, including food protein and commensals, and harmful antigens such as pathogens. However, patients with celiac disease (CD) develop an intolerance to gluten proteins which results in a pro-inflammatory T-cell mediated immune response with production of anti-g
Alcohol dependence has traditionally been considered a brain disorder. Alteration in the composition of the gut microbiota has recently been shown to be present in psychiatric disorders, which suggests the possibility of gut-to-brain interactions in the development of alcohol dependence. The aim of the present study was to explore whether changes in gut permeability are linked to gut-microbiota composition and activity in alcohol-dependent subjects. We also investigated whether gut dysfunction is associated with the psychological symptoms of alcohol dependence. Finally, we tested the reversibility of the biological and behavioral parameters after a short-term detoxification program. We found that some, but not all, alcohol-dependent subjects developed gut leakiness, which was associated with higher scores of depression, anxiety, and alcohol craving after 3 wk of abstinence, which may be important psychological factors of relapse. Moreover, subjects with increased gut permeability also had altered composition and activity of the gut microbiota. These results suggest the existence of a gut–brain axis in alcohol dependence, which implicates the gut microbiota as an actor in the gut barrier and in behavioral disorders. Thus, the gut microbiota seems to be a previously unidentified target in the management of alcohol dependence.
eding/fasting cycle influence host metabolism and contribute to obesity and metabolic diseases. However, fundamental characteristics of this relationship between the feeding/fasting cycle and the gut microbiome are unknown. Our studies show that the gut microbiome is highly dynamic, exhibiting daily cyclical fluctuations in composition. Diet-induced obesity dampens the daily feeding/fasting rhythm and diminishes many of these cyclical fluctuations. Time-restricted feeding (TRF), in which feeding is consolidated to the nocturnal phase, partially restores these cyclical fluctuations. Furthermore, TRF, which protects against obesity and metabolic diseases, affects bacteria shown to influence host metabolism. Cyclical changes in the gut microbiome from feeding/fasting rhythms contribute to the diversity of gut microflora and likely represent a mechanism by which the gut microbiome affects host metabolism. Thus, feeding pattern and time of harvest, in addition to diet, are important parameters when assessing the microbiome’s contribution to host metabolism.
Many common diseases, such as asthma, diabetes or obesity, involve altered interactions between thousands of genes. High-throughput techniques (omics) allow identification of such genes and their products, but functional understanding is a formidable challenge. Network-based analyses of omics data have identified modules of disease-associated genes that have been used to obtain both a systems level and a molecular understanding of disease mechanisms. For example, in allergy a module was used to find a novel candidate gene that was validated by functional and clinical studies. Such analyses play important roles in systems medicine. This is an emerging discipline that aims to gain a translational understanding of the complex mechanisms underlying common diseases. In this review, we will explain and provide examples of how network-based analyses of omics data, in combination with functional and clinical studies, are aiding our understanding of disease, as well as helping to prioritize diagnostic markers or therapeutic candidate genes. Such analyses involve significant problems and limitations, which will be discussed. We also highlight the steps needed for clinical implementation.
Professor of Computational Biology and Bioinformatics, Department of Biostatistics, Harvard University, Dana-Farber Cancer Institute (Watch Webinar "Integrative Systems Approaches to Network Modeling of Biological Processes" by John Quackenbush,...
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The ISME Journal: Multidisciplinary Journal of Microbial Ecology is the official Journal of the International Society for Microbial Ecology, publishing high-quality, original research papers, short communications, commentary articles and reviews in the rapidly expanding and diverse discipline of microbial ecology.