Microbiome–Gut Dissociation in the Neonate: Obesity and Coeliac Disease as Examples of Microbiome Function Deficiency Disorder

Abstract

The purpose of this article is to provide a direction for translational research based on an analysis of the nature of complex, immune-related conditions such as obesity and coeliac disease. In essence, it seems that the prevalence of these non-communicable diseases is related to the degradation of the microbiome during the industrialisation of society, and that their nature can be used to infer the functions of the “pre-industrial” microbiome. Based on this analysis, the key point is the necessity for the fully functioning microbiome, acting alongside the parental genetic inheritance of the child, to be in place immediately after birth. In our view, this is achieved by the seemingly accidental process of maternal microbial inheritance during normal birth. Note, however, that this is not possible if the microbiome of the mother is itself degraded following previous problems. Under these conditions the health of a child may be affected from the moment of birth, although, with the exception of atopic diseases, such as eczema and food allergy, the consequences may not become apparent until late childhood or as an adult. In this way, this microbiome function deficiency hypothesis incorporates the epidemiological observations of David Strachan and David Barker in that their onset can be traced to early childhood. Coeliac disease has been chosen as an illustrative example of a multifactorial disorder due to the fact that, in addition to a series of immune system manifestations and a potential problem with food absorption, there is also a significant psychological component. Finally, it is worth noting that an ingestible sensor calibrated to the detection of interkingdom communication molecules (semiochemicals) within the intestine may offer a practical way of assessment and, perhaps, amelioration of at least some of the consequences of non-communicable disease.

On the Inheritance of Microbiome-Deficiency: Paediatric Functional Gastrointestinal Disorders, the Immune System and the Gut–Brain Axis

“…As the spread seems to be too fast for classic genetic diseases, this raises the question of maternal microbial inheritance: the microbes transfer from the mother to the neonate during the birth process; additionally, the role of seminal microbiome has more recently been investigated not only as an epigenetic factor [12], but also for the optimal development of the preconception environment [13,14]. Our previous work in this field used the concept of microbiome-function deficiency to draw together the links between obesity and coeliac disease, the latter involving both functional gastrointestinal and immune system disorders and potentially poor mental health [15]. As indicated above, it is important to note that due to the poor absorption of nutrition, sufferers from coeliac disease may present with a BMI (body mass index) in the nominally healthy range [16].…”

Feeding Our Microbiota: Stimulation of the Immune/Semiochemical System and the Potential Amelioration of Non-Communicable Diseases

“…In support of this thesis, we further suggest that the rationale for the microbiome is to add the flexibility of horizontal gene transfer at the microbial level to the relative stability of multicellular evolution by the inheritance of acquired characteristics, thus combining the benefits of operating both above and below what has been called the Darwinian threshold [ 74 ]. Note that the failure of the microbiome is at an evolutionary level, albeit that this failure is reflected in a myriad of seemingly different conditions [ 75 ]. Of course, this is closely analogous to the holobiont concept pioneered by Lynn Margulis [ 76 , 77 , 78 ].…”

“…In the light of Barker’s original observation of the “fetal and infant origins of adult disease”, it seems likely that both the immune system and the microbiota–gut–brain axis start to develop immediately after birth [ 75 ], and that any lack of microbial function will have a negative impact on the eventual health of the individual, to a greater or lesser extent [ 29 ]. The concept of mutualism implies two parallel interactions that benefit both components.…”

“…By contrast, the failure of the dual immune/semiochemical control system leads to a complex series of health problems normally classified by the single most troublesome variety. Thus, while coeliac disease is classed as a problem of the intestine [ 80 ], immune system problems can, nonetheless, occur anywhere around the body, along with problems of food absorption and of depression [ 75 ]. It is important to note that these non-communicable diseases are modern due only to their prevalence, as occasional examples of similar diseases can be found dating from earlier times [ 29 ].…”

“…By contrast, in the presence of dysbiosis, with weaker gut–brain axis and/or less efficient production of semiochemicals, a less readily digested prebiotic-like substance will be required to produce a similar signal from the ingestible sensor [ 141 ]; results can then be combined with - omic data and theoretical models based on metabolic fluxes [ 129 ]. Significantly, however, prior microbiome–gut dissociation may mean that even an enhanced semiochemical signal may have a limited effect on disease symptoms [ 75 ]. While animals could be used in such studies, a recent observation has illustrated a difference in the outcome of trials involving genetically identical animals raised in two different laboratories.…”