Search the KHIT Blog

Tuesday, June 12, 2018

Omics update: microbiome implications for clinical care

I've addressed the broad topic of "Omics" sciences and technologies a number of times in prior posts. On a personal level, earlier in the year, an article in Science Magazine spoke to issues in cancer therapies that seem to be adversely impacted by gut microbiota bearing certain genetic profiles. I found it of particular interest, given that they gave the example of attenuating or neutralizing microbiome impacts on the Folfirinox chemo that my (now late) daughter was undergoing.

More stuff to have to know and consider.

Just saw a book review in a new issue of Science.
Probing the Microbial

Angela Douglas is an internationally recognized expert on symbiosis, with a number of foundational texts to her name (1, 2). In her new book, Fundamentals of Microbiome Science, Douglas synthetizes data from the burgeoning field of microbiome science in eight highly informative chapters. Topics include the origins of the animal microbiome, what we know about the microbiome's interactions with the immune system, hints at how microbes drive animal behavior, and how the gut microbiota are involved in gut-brain communication. The book also clearly delineates the influence of the microbiome in determining human health and disease.

The microbiome revolution is expanding at breakneck speed and moving from “the study of correlation to causation and mechanism.” For example, mice lacking the leptin gene, which regulates satiety, consume more food and become obese. When the microbiota of obese mice are transferred to lean mice, the mice eventually become obese.

The reciprocal mechanisms involved in the interactions between the immune system and the microbiota are just beginning to be understood. In mammals, for example, the production of immunoglobulin A prevents contact of the microbiota with the epithelial cells of the gut, thus impeding microbe access to internal organs. Other innate immune effectors, including antimicrobial peptides, lectins, and certain enzymes, complement this effect, but many other factors (e.g., age of host, sex, and genotype) could also influence the outcome. The immune system can thus promote, tolerate, or inhibit the composition of the microbiota. In contrast, the microbiota can “promote or dampen immune system function,” and the effects of microbial products on the regulation of immune effectors have been implicated in this process…

This one is heavy duty.

This book is about animal microbiomes: the microorganisms that inhabit the body of animals, including humans, and keep their animal hosts healthy. In recent years, animal microbiomes have become a hot topic in the life sciences. Academic, commercial, and funding institutions are investing in major microbiome research centers and funding initiatives; microbiomes are the topic of special issues in journals, conference symposia, and new undergraduate and graduate courses; microbiomes have twice been a Science journal “breakthrough of the year” (in 2011 and 2013); and the US National Microbiome Initiative was announced from the White House in May 2016. Why all the excitement about microbiomes? The reasons are twofold: microbiome science provides a radically different way to understand animals, and it offers the promise of novel therapies, especially for human health…

1.4. Scope of This Book

The realization that every animal is colonized by microorganisms that can shape its health and well-being is transforming our understanding of animal biology. The purpose of this book is to provide some initial explanations and hypotheses of the underlying animal-microbial interactions. For this, we need multiple disciplinary perspectives.

We start with evolutionary history in chapter 2. The propensity of animals to associate with microorganisms has ancient roots, derived from both the predisposition of all eukaryotes to participate in associations and, likewise, the tendency of many bacteria to interact with different organisms, often to mutual benefit. Chapter 2 outlines the patterns of these interactions, especially in taxa related to animals and basal animal groups. Interactions are mediated by chemical exchange, enhancing access to energy and nutrients and providing chemical information that enables the interacting organisms to anticipate and respond adaptively to environmental conditions. Many of these core interactions were firmly established in the ancestor of animals. The multicellular condition of animals, sophisticated immunological function of even basal animals, and key animal innovations, including the polarized epithelium and the gut, play important roles in shaping the pattern of animal-microbial interactions.

Although all animals are associated with microorganisms, we know more about the microbiome of humans than any other animal. Chapter 3 addresses current understanding of the role of the microbiome in human health. Studies of the microbiology of humans combined with experimental analyses of model animals are revealing complex problems—and some solutions. The complexity lies in the great diversity of microorganisms within each individual human, as well as considerable among-individual variation; and the importance of the microbiome is reinforced by the increasing evidence for microbial involvement in some diseases, especially metabolic and immunological dysfunctions. Western lifestyles, including diet and antibiotic treatment, have been argued to contribute to the incidence of microbiome-associated diseases, with opportunities for microbiological restoration by microbial therapies.

Our understanding of interactions between animals and the microbiome is most developed in relation to the immune system, and this is the focus of chapter 4. It is now apparent that animal immune system is a key regulator of the abundance and composition of the microbiota, and that immunological function is strongly regulated by the composition and activities of the microbiome. The immune system cannot be understood fully except in the context of the microbiology of the animal. Furthermore, this highly interactive system is overlain by microbial-mediated protective functions, essentially comprising a second immune system.

Chapter 5 investigates the role of the microbiome in shaping animal, including human, behavior. It has long been known that pathogens can drive animal behavior, and there is now increasing evidence that resident microorganisms can have similar, although often more subtle, effects. Research has focused primarily on three aspects of animal behavior: feeding behavior, chemical communication among animals, especially in relation to social interactions, and the mental well-being of mammals, including humans. As chapter 5 makes clear, this topic has attracted tremendous levels of interest, but fewer definitive data.

The impacts of animal-associated microorganisms on host health and their interactions with the immune system and nervous system of animals (chapters 3–5) have one overriding theme in common: that these interactions are complex, with multiple interacting variables. This complexity can often appear to defy comprehension. Chapter 6 discusses the ecological approaches that have the potential to solve many of these problems of complexity. Treating the animal as an ecosystem, we can ask multiple questions: what are the ecological processes that shape the composition and diversity of microbial communities, and how do these properties of the microbial communities influence overall function of the ecosystem? Research on complex microbiomes, especially in the animal gut, as well as one-host-one-symbiont systems are revealing the role of interactions among microorganisms and interactions between the microorganisms and host in shaping the diversity of the microbiome. Furthermore, the response of individual taxa and interactions can influence the stability of communities to external perturbations, ranging from the bleaching susceptibility of shallow-water corals to the gut microbiota composition of humans administered with antibiotics.

In chapter 7, the evolutionary consequences of animal-microbial associations are considered. There is a general expectation that the fitness of both animal and microbial partners is enhanced by these associations largely through the reciprocal exchange of services. Nevertheless, hosts can exploit their microbial partners, and there are indications that animals can be addicted to their microbial partners. At a broader scale, this chapter investigates how these associations affect the rate and pattern of evolutionary diversification of the microbial and animal partners. In addition to evidence for coevolutionary interactions and facilitation of horizontal gene transfer, various studies point to a direct role of microbiota in interrupting gene flow and speciation by both prezygotic and postzygotic processes.

Finally, chapter 8 addresses the implications of the microbiology of animals and some key priorities for future research. It is now abundantly clear that the microbiome has pervasive effects on the physiological and developmental systems of animals and the resultant animal phenotype. One of the big biological questions in the life sciences today concerns how the phenotype of an animal maps onto its genotype and the underlying physiological and developmental mechanisms. The answers to this question will require the integration of the microbiome with the traditional animal-only explanations of animal function. As this book illustrates, the technologies and concepts to achieve this intellectual transformation of animal biology are largely in place. Why is this integration of disciplines needed? Beyond the fundamental priority to understand and explain, the microbiome offers important, but currently untapped, routes to promote human health and to mitigate and manage some of the damaging effects of human activities on our environment.

Douglas, Angela (2018-05-14T23:58:59). Fundamentals of Microbiome Science: How Microbes Shape Animal Biology (Kindle Locations, 114-121, 333-386). Princeton University Press. Kindle Edition.
Downstream from the research science, we'll likely see another "omics" subspecialty dealing with the microbiome and its implications for front-line clinical care. Docs in the "productivity treadmill" exam rooms will neither have the expertise nor the time to ruminate on these details directly.


Of course, this stuff will inevitably bring us back around to Health IT, specifically "AI." Specifically, recall my prior "There IS no Precision Medicine without AI."


Recall my prior post "Holmes and Balwani should be indicted." An interview by Vanity Fair's Nick Bilton with "Bad Blood" author John Carryrou.
Silicon Valley is notoriously full of founders who exaggerate, intentionally lie to the media, and dupe investors, and even Congress. But there are few stories that rival the fraud behind Theranos, the blood-testing company once worth $10 billion, and now worth nothing. John Carreyrou, author of a new book, "Bad Blood," joins us to explain how the company's CEO, Elizabeth Holmes, defrauded everyone who came into her orbit, how she might still end up behind bars, and he answers the question on everyone's mind: Is Holmes a sociopath?
"According to Carreyrou, Holmes is currently waltzing around Silicon Valley, meeting with investors, hoping to raise money for an entirely new start-up idea. (My mouth dropped when I heard that, too.)"

More to come...

No comments:

Post a Comment