Abstract
The study of the interactions between the neuroendocrine and immune systems is a highly interdisciplinary research endeavor, in which the boundaries between the systems being studied become blurred. We address a common scientific perspective in dealing with intertwined complex systems, namely the conceptual approach in science that treats each system (e.g., nervous, immune, endocrine systems) as separate units or “building blocks” with unique functions that correspond to specific structures. While there are merits to this way of decomposing complex systems, there are several reasons why such an approach is limited when trying to recompose a physiological system that is engaged in intricate co-functioning and that is the result of co-development, and co-evolution, not just between these systems, but with the gut microbiota as well. Our suggestion is to take an alternative ecological evolutionary developmental approach to the neuro-endocrine-immune-microbiota system (NEIMS) as a whole, which can serve as complementary to the predominant building block perspective.
Author’s major contributions: GPG first draft, sections 2.2 & 2.5; FB section 2.3, edited draft; LC section 2.1 & 2.4, edited draft; JPK section 2.4, edited draft
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- 1.
“It’s Even Less in Your Genes,” The New York Review, May 26, 2011 issue, https://www.nybooks.com/articles/2011/05/26/its-even-less-your-genes/ [accessed: 28-01-2022].
- 2.
Historically, various terms have been used reflecting slightly different approaches, from psychoneuroimmunology and neuroimmunomodulation, which, at least initially, were rather top-down in nature, to immunopsychiatry, being more bottom-up (Konsman 2019; Pariante 2015). However, in all cases, some interactions between neuroendocrine and immune systems are invoked or assumed. Therefore, we propose to use the term “neuroimmune” as shorthand for these different approaches while being well aware that neuroimmunology refers to a scientific field.
- 3.
Microorganisms were initially studied (mainly in medicine) in their role as pathogens (consider, for instance, the studies of Koch and Pasteur). This means that they were studied in isolation without consideration of the structures they usually assume in nature, i.e. biofilms. Indeed, biofilms were first proposed by microbial ecologists and then adapted and adopted in clinical settings. Microorganisms are now seen as systems in virtue of their ecological nature. This is another example of how the way to look at things can “change” the nature of the objects of scientific investigations, including the methods to study those entities.
- 4.
It is essential here to recall the recent developments in computational biology and systems biology. The tools used in computational and system biology by these research sectors allow one to consider and analyze vast amounts of data and to examine and manipulate some properties by abstracting vast amounts of them from the objects of scientific investigation. This practice has led some to believe that this was the main way to deal with the complexity of biological phenomena and to avoid simplistic reductionism. The discussion of these aspects is too extensive to be fully reported here. However, it is enough for us to point out that, while it is certainly true that, while these approaches have made it possible to build new “privileged observation points” on biological phenomena (not otherwise investigable), it is also important to remember that complexity is not just a question of quantity or computational capacity, but something that (unlike “complication”) is inherently irreducible. By providing a complementary look at the reductionism of certain compartmentalized and mechanistic investigations, computational methods will enable researchers to have a more authentic picture of their field of investigation, because even if they employ reductionist methods (the use of which is often a harbinger of discoveries), they will be able to give a broader and more legitimate meaning to their results within the general framework.
- 5.
This does not necessarily imply that a particular way of dividing subsystems was the result of inattention, the lack of a critical attitude or methodological negligence, but instead reflects the need to be mindful of the nature and necessity of boundaries. Even if past divisions have successfully worked for certain experimental results, the adopted partition still calls for continuous, additional justification.
- 6.
In chimerism, each cell population retains its own characteristics, given that they are genetically distinct because they originate from different zygotes. Thus, the resulting organism is a mixture of differently matched regions. On the other hand, in genetic mosaicism, different cells, with a diverse genetic heritage, arise from the same zygote.
- 7.
Even though this structural comprehension of the immune system is possible, and although immune cells share developmental origins (and evolutionary as well), their definition as such relies more upon their capabilities and mutual interactions.
- 8.
This does not entail a naïve (and not very useful) form of reductionism for which every organismic activity is attributable to the immune system. On the contrary, if the immune system extends to the whole body, this means that one cannot ignore the immune system to provide a complete explanation of many activities of the organism itself. It will be the main task, for future science, to clarify the aspects and mechanisms by which this happens.
- 9.
Finally, although not addressed here, the organization of the gut between the endocrine, immune, and nervous components may also play a role in the emergence of proto-awareness in animals—a topic to be discussed in the future.
- 10.
From a systemic point of view, however, it is important to remember that the microbiota is not only involved in the modulation of the local or tissue-specific response. Indeed, treatment with antibiotics has, in fact, shown how the decrease of the microbiota (both in terms of its number and composition/diversity) has a global impact on the activities of the immune system at the level of the whole organism. This occurs both in situations of inflammatory and defensive response and concerning the general and regulatory functions of the immune system in its broadest sense. There are now countless studies concerning the potential contribution of the microbiota (with either protective or promoting effects) with conditions such as chronic, metabolic, autoimmune, neurodegenerative diseases, and cancer.
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Greslehner, G.P., Boem, F., Chiu, L., Konsman, J.P. (2023). Philosophical Perspectives on Neuroendocrine–Immune Interactions: The Building Block Model and Complementary Neuro-Endocrine-Immune-Microbiota Systems Approaches. In: Konsman, J.P., Reyes, T.M. (eds) Neuroendocrine-Immune System Interactions. Masterclass in Neuroendocrinology, vol 13. Springer, Cham. https://doi.org/10.1007/978-3-031-21358-8_2
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