Elsevier

Medical Hypotheses

Volume 108, October 2017, Pages 133-143
Medical Hypotheses

The colon revisited or the key to wellness, health and disease

https://doi.org/10.1016/j.mehy.2017.07.032Get rights and content

Abstract

The hypothesis being advanced in this paper is that there is a new medical paradigm emerging from the biomedical research carried out in this century, mainly due to the explosion of the so called “omics” and associated techniques. The main idea is that there is a common pathway from wellbeing and health to chronic disease (“chronopathy”) and even to death, which comprises following steps: 1) unhealthy diet, sedentary life style and permanent exposition to xenobiotics and all kinds of noxious stimuli;  2) intestinal dysbiosis;  3) alteration of the intestinal mucus layer (especially that of the colon);  4) disruption of the endothelial tight junctions;  5) metabolic endotoxemia + bacterial translocation;  6) inflammation;  7) exacerbation of the enteric nervous system (ENS) and consequent maladaptation and malfunctioning of the colon;  8) epigenetic manifestations;  9) “chronopathy” and premature death. Therefore, in order to maintain a good health or to improve or even reverse chronic diseases in a person, the main outcome to look for is a homeostatic balance of the intestinal microbiota (eubiosis), most of which is located in the colon. Lynn Margulis was one of the main scientists to highlight the importance of the role played by bacteria not only in the origin of all biological species now present on earth, but also on their role in global homeostasis. Bacteria do not rely on other living beings for their existence, while the latter depend completely on the former. Humans are no exemption, and new evidence emerges each day about the pivotal role of intestinal microbiota in human health, disease and, in general, in its wellbeing. The following facts about intestinal microbiota are nowadays generally accepted: there are about 10 times more bacteria in the gut than human cells in every human being; the microbioma is about 100–150 times bigger that the human genome, and there is a clear link between intestinal microbiota and many of the most common chronic diseases, from obesity and diabetes to depression and Parkinson disease and different kinds of cancer. The main implication of this theory is that we should become a sort of microbiota farmers, that is, we ought to be more conscious of our intestinal microbiota, take care of it and monitor it permanently. Thus, as part of our good life habits (healthy eating, physical exercise), we should probably undergo periodic seasons of fasting and colon cleansing, as it was common in older times.

Introduction

About two and half millennia ago, Hippocrates, who is considered the father of Western medicine, is credited with having stated that “all diseases begin in the gut”. To a good extent, science of the twenty first century is proving him right. The physical and functional condition of any living being is the result of its dynamic interaction with its closer environment. In our case, we, human beings, have as our closer environment the planet, named Gaia after the theory of James Lovelock [1]. Between what we would call “ourselves” and that environment, we find the intestinal microbiota, and more specifically, the colonic microbiota, as an active and, it seems, to a good extent, determinant interface between these two worlds, which not only reflects but also modulates that interaction. The influence of the environment on the microbiota is determined, in first place, by the quantity and quality of physical and chemical agents that, directly or indirectly, act upon it like electromagnetic radiations (light and cosmic, as well as gamma and X rays), temperature, humidity, water, air, nutrients, drugs and all kind of xenobiotics and contaminants. The effect of this interaction between environment and microbiota is firstly manifest in the composition of this microbiota, which, subsequently, will produce changes in its near as well as in far from the colon structures of the human body. In Fig. 1, we highlight the main components of those near structures present in the colonic wall: mucus layer, mucosa, submucosa, muscularis and serosa, with some of their most prominent corresponding substructures.

The role not only of the colon as an organ, but of each of the structures and substructures of its wall, are far from being completely understood and only very recently they have capture the attentions of many scientists around the world [2]. Based on this, we propose a common pathway for chronic non communicable diseases (CNCDs) as shown in Fig. 2. This pathway complements some of the aspects proposed by [3] for the metabolic disease investigated in rats by this group. The sequence they proposed as a hypothesis on bacterial induced metabolic disease was: 1) high fat feeding  2) change in gut flora  3) increased intestinal permeability  4) increased endotoxemia  5) inflammation  6) metabolic disorders.

In our model, we add the following aspects:

  • a)

    Disruption of the colonic mucus layer between steps 2) and 3);

  • b)

    Bacterial translocation between steps 4) and 5), simultaneously with “increased endotoxemia”;

  • c)

    Exacerbation of the enteric nervous system (ENS), also known as “our second brain”;

  • d)

    Maladaptation and abnormal responses of the myenteric tissue like the “occult reflex” (see section “Colon maladaptation and dysfunction”).

For CNCDs in general, we will then have: 1) unhealthy diet (rich in fat, refined carbohydrates and red meat, and low in fiber) [4], low amount or lack of exercise [5], over emotional stress [6], and permanent exposition to xenobiotics and all kinds of noxious stimuli [7];  2) dysbiosis (alteration in the ratio of “harmful” and “beneficial” commensal bacteria, [8];  3) alteration of the mucus layer [9], [10]  4) disruption of the tight junctions [11] with increased intestinal permeability [12]  5) metabolic endotoxemia + bacterial translocation [13]  6) inflammation [4] also termed “meta-inflammation” [14] or “low grade inflammation” [15]  7) Exacerbation of the enteric nervous system (ENS) and maladaptation and malfunctioning of the colon [16];  8) individual genetic and epigenetic predisposition [17]  9) CNCDs or “chronopathy”. (Note: the term “chronopathy” does not exist in the medical vocabulary but we would like to use it to design the condition of being chronically ill, and “chronopath” to design a person being chronically ill).

Section snippets

The hypothesis

Our hypothesis, as stated in the title, is that the colon, including its associated microbiota as an integral part of it, is the key to wellness, health and disease. This implies not only that we should consciously take care of it,1 but also to monitor it permanently. Detection of early perturbations of colon

Bad life habits as risk factors

Epidemiology has proven that most CNCDs have some common risk factors and that they are preventable [19], [20]. [21] refer to “…man-made environments, their byproducts and/or lifestyles encouraged by these, some of which may be detrimental to human health” as “anthropogens” and it is considered that 4 of them (tabaquism, alcoholism, poor diet and lack of physical exercise) can explain the majority of deaths produced by a group of four types of diseases: cardiovascular diseases, cancer, chronic

Disruption of the intestinal mucus layer

An early consequence of dysbiosis is the disruption of the mucus layer that covers the intestinal wall, which, in reality, is a bilayer: the outer (luminal) layer is the natural habitat of the intestinal microbiota, and the inner (epithelial) layer, which acts as a physicochemical barrier to it [34], [35] . In the colon, this bilayer is uniform, continuous and very thick (upto 830 µm, as measured in rats, [36] , while in the small intestine it is discontinuous and thinner (about 120 µm in rats),

Colon maladaptation and dysfunction

The colon, as any living structure, reacts with adaptation to noxious stimuli, especially when they are chronic. In the previous section, we have already mentioned that inflammation in the colon is one of the initial responses to microbial dysbiosis and that it adopts the form of chronic low grade inflammation, also known as “metainflammation”. But the nervous system and the muscle layers of the colon wall also participate in the reactions to those noxious stimuli. Both structures show a good

Microbiota-gut-brain axis modulation by enteric microbiota and its mediation by the enteric nervous system (ENS or our “second brain”)

The double way cross communication between intestine and brain, called the “microbiota-gut-brain axis” [55], is mediated by different pathways and mechanisms: immunological, neural, biochemical and endocrine [26]. On one side, it has to be taken in account that the ENS can perform many of its functions in an autonomous way, but its functioning is normally displayed in a permanent cross talk with the central nervous system (CNS) as well as with the endocrine and immune systems. Both sympathetic

Colon cleansing or microbiota recomposition

In this section, we would like to show some preliminary data obtained in the process of implementing a fat reduction program at the University of Caldas (UC), where authorities have been concerned with the increasing prevalence of overweight among its students, specially affecting the female population. We have monitored students since 1995 and estimate a present prevalence of women with BMI  25 of about 22,0% and a prevalence of women with percentage body fat (%BF)  32% of about 68%. We are,

Consequences of the hypothesis and discussion

If our hypothesis were to be confirmed, its main implications would be in the field of: a) how to keep people in a general status of wellbeing and prevent disease, b) how to implement the screening and pre-screening of CNCDs, especially cancer, and c) how to treat people who have started to develop symptoms of “chronopathy”.

An eubiotic microbiota would probably reflect a good, healthy life style, although, as we have seen, exposoms along life span can influence it. But, whatever one‘s personal

Summary and final remarks

At present and worldwide, the burden of CNCDs is enormous and increasing. They constitute the first cause of death and have practically collapsed health systems at a global scale. Although we cannot blame individuals for the epidemic of CNCDs, as we live in what we could call a “chronopathogenic” society, individuals and communities continue to struggle with their effects at a personal and local level. Therefore, although we should ideally fight for a radical change in society, this is probably

Conflicts of interest

The authors state that they have no conflicts of interest.

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