Seeing the wood for the trees: A new way to view the human intestinal microbiome and its connection with non-communicable disease

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Across the world there is an increasingly heavy burden of noncommunicable diseases related to obesity, mental health, and atopic disease. In a previous publication, we followed the developing idea that that these conditions arise as our microbiome loses diversity, but there seems to be no generally applicable way to assess the significance of this loss. Our work revisited the findings of the African studies by Denis Burkitt who reported that the frequency of what he called Western diseases were inversely proportional to the average faecal volumes of affected populations. Although he ascribed this to fibre in the diet, it now seems more likely that the drop in faecal volume with the onset of disease is due to the loss of a fully functioning microbiome. We suggested that the microbiome could be considered to be a single mutualistic microbial community interacting with our body by two complementary sets of semiochemicals, i.e., allomones to feed the microbiota by facilitating the efficient transfer of nutrition through the gut and kairomones to calibrate our immune system by an as yet unknown mechanism. The bioactive compounds, dopamine and serotonin, are known to be present in the gut lumen under the influence of intestinal microbiota and we suggest that these are part of this allomone-like system. In light of this possibility, it is of critical importance to develop a method of quantifying the microbiome effectiveness. Ingestible sensors consist of a miniaturized detector and transmitter packed into a capsule that is swallowed and tracked through the intestine. The aim of this article is to explore the possible development of such ingestible detectors for these or other compounds that can act as a surrogate marker for microbiome effectiveness. We consider that the ability to provide real-time quantitative information on the interaction of the microbiome with different nutrients promises to be a valuable new tool to unravel the mystery of these noncommunicable illnesses, i.e., microbiome-function deficiency diseases.

Section: Microbiome Diversity: Probiotics and Sentinel Cellsmentioning

confidence: 99%

Section: Microbiome Diversity: Probiotics and Sentinel Cellsmentioning

confidence: 99%

Section: The Mutualistic Microbiome: Dysbiosismentioning

confidence: 99%

Section: The Mutualistic Microbiome: Dysbiosismentioning

confidence: 99%

Section: Introduction: the Microbiome In Health And Diseasementioning

confidence: 99%

See 3 more Smart Citations

Measuring Microbiome Effectiveness: A Role for Ingestible Sensors

Smith¹,

Jheeta²

2020

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Microbiome–Gut Dissociation: Investigating the Origins of Obesity

Smith¹,

Jheeta²

2021

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The reduction of excessive weight remains a major public health challenge, with control currently limited to a calorie reduction strategy. Currently, attempts are being made at revisiting the fibre hypothesis based on the African studies of Denis Burkitt, that the lack of dietary fibre in the modern diet was responsible for the occurrence of obesity and many of the other non-communicable diseases of what he called “Western civilization”. However, the dilemma is that Burkitt himself stressed that other peoples of his day, such as the Maasai, remained healthy without consuming such high fibre diets. Equally, the present obesity epidemic is accompanied by diseases of a malfunctioning immune system and of poor mental health that do not seem to be adequately explained simply by a deficiency of dietary fibre. Though unknown in Burkitt’s day, an increasing degradation of a mutualistic intestinal microbiome would offer a better fit to the observed epidemiology, especially if the microbiome is not effectively passed on from mother to child at birth. Taking the broader view, in this article we posit a view of the microbiome as a cofactor of mammalian evolution, in which a maternal microbial inheritance complements the parental genetic inheritance of the animal, both engaging epigenetic processes. As this would require the microbiome to be fully integrated with the animal as it develops into an adult, so we have a meaningful evolutionary role for the microbiome–gut–brain axis. By a failure to correctly establish a microbiome–gut interface, the inhibition of maternal microbial inheritance sets the scene for the future development of non-communicable disease: compromised immune system function on the one hand and dysfunctional gut–brain communication on the other. The basic principle is that the fully functioning, diverse, microbiome achieves interkingdom communication by the generation of messenger chemicals, semiochemicals. It is envisaged that the in situ detection of these as yet ill-defined chemical entities by means of an ingestible sensor would indicate the severity of disease and provide a guide as to its amelioration.

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

Smith¹,

Palacios-Pérez

Jheeta³

2022

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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.