Like the majority of non-communicable diseases that have recently gained attention, functional gastrointestinal (GI) disorders (FGID) in both children and adults are caused by a variety of medical conditions. In general, while it is often thought that common conditions such as obesity may cause other problems, for example, asthma or mental health issues, more consideration needs to be given to the possibility that they could both be brought on by a single underlying problem. Based on the variations in non-communicable disease, in recent years, our group has been revisiting the exact role of the intestinal microbiome within the Vertebrata. While the metabolic products of the microbiome have a role to play in the adult, our tentative conclusion is that the fully functioning, mutualistic microbiome has a primary role: to transfer antigen information from the mother to the neonate in order to calibrate its immune system, allowing it to survive within the microbial environment into which it will emerge. Granted that the microbiome possesses such a function, logic suggests the need for a robust, flexible, mechanism allowing for the partition of nutrition in the mature animal, thus ensuring the continued existence of both the vertebrate host and microbial guest, even under potentially unfavourable conditions. It is feasible that this partition process acts by altering the rate of peristalsis following communication through the gut–brain axis. The final step of this animal–microbiota symbiosis would then be when key microbes are transferred from the female to her progeny, either live offspring or eggs. According to this scheme, each animal inherits twice, once from its parents’ genetic material and once from the mother’s microbiome with the aid of the father’s seminal microbiome, which helps determine the expression of the parental genes. The key point is that the failure of this latter inheritance in humans leads to the distinctive manifestations of functional FGID disorders including inflammation and gut motility disturbances. Furthermore, it seems likely that the critical microbiome–gut association occurs in the first few hours of independent life, in a process that we term handshaking. Note that even if obvious disease in childhood is avoided, the underlying disorders may intrude later in youth or adulthood with immune system disruption coexisting with gut–brain axis issues such as excessive weight gain and poor mental health. In principle, investigating and perhaps supplementing the maternal microbiota provide clinicians with an unprecedented opportunity to intervene in long-term disease processes, even before the child is born.

It is increasingly likely that many non-communicable diseases of humans and associated animals are due to the degradation of their intestinal microbiomes, a situation often referred to as dysbiosis. An analysis of the resultant diseases offers an opportunity to probe the function of these microbial partners of multicellular animals. In our view, it now seems likely that vertebrate animals and their microbiomes have coevolved throughout the Ediacaran–Cambrian transition and beyond, operating by semiochemical messaging between the multicellular host and its microbial community guest. A consideration of the overall role of the mutualistic intestinal microbiome as an enclosed bioreactor throws up a variety of challenging concepts. In particular: the significance of the microbiome with respect to the immune system suggests that microeukaryotes could act as microbial sentinel cells; the ubiquity of bacteriophage viruses implies the rapid turnover of microbial composition by a viral-shunt mechanism; and high microbial diversity is needed to ensure that horizontal gene transfer allows valuable genetic functions to be expressed. We have previously postulated that microbes of sufficient diversity must be transferred from mother to infant by seemingly accidental contamination during the process of natural birth. We termed this maternal microbial inheritance and suggested that it operates alongside parental genetic inheritance to modify gene expression. In this way, the adjustment of the neonate immune system by the microbiome may represent one of the ways in which the genome of a vertebrate animal interacts with its microbial environment. The absence of such critical functions in the neonate may help to explain the observation of persistent immune-system problems in affected adults. Equally, granted that the survival of the guest microbiome depends on the viability of its host, one function of microbiome-generated semiochemicals could be to facilitate the movement of food through the digestive tract, effectively partitioning nutrition between host and guest. In the event of famine, downregulation of microbial growth and therefore of semiochemical production would allow all available food to be consumed by the host. Although it is often thought that non-communicable diseases, such as type 2 diabetes, are caused by consumption of food containing insufficient dietary fibre, our hypothesis suggests that poor-quality food is not the prime cause but that the tendency for disease follows the degradation of the intestinal microbiome, when fat build-up occurs because the relevant semiochemicals can no longer be produced. It is the purpose of this paper to highlight the possibility that the origins of the microbiome lie in the Precambrian and that the disconnection of body and microbiome gives rise to non-communicable disease through the loss of semiochemical signalling. We further surmise that this disconnect has been largely brought about by heavy metal poisoning, potentially illuminating a facet of the exposome, the sum total of environmental insults that influence the expression of the genetic inheritance of an animal.

This is a report from NoRCELs Blue Earth Project symposium BEP2022 held online on January 8th, 2022. We are reporting the outcome pertaining to the following question: Is Humanity Settling its own Fate on Ecological Survival? A succinct conclusion drawn is that the Earth is facing the sixth mass extinction of flora and fauna; this being different from the previous five extinctions, in that it is entirely due to mankinds activities. Five invited eminent speakers delivered their input, highlighting the fact that there is extensive deterioration of the environment at large, coupled with an unprecedented demise of ecosystems leading to the extinction of species across the globe.

While the importance of the intestinal microbiome has been realised for a number of years, the significance of the phrase microbiota–gut–brain axis is only just beginning to be fully appreciated. Our recent work has focused on the microbiome as if it were a single entity, modifying the expression of the genetic inheritance of the individual by the generation of interkingdom signalling molecules, semiochemicals, such as dopamine. In our view, the purpose of the microbiome is to convey information about the microbial environment of the mother so as to calibrate the immune system of the new-born, giving it the ability to distinguish harmful pathogens from the harmless antigens of pollen, for example, or to help distinguish self from non-self. In turn, this requires the partition of nutrition between the adult and its microbiome to ensure that both entities remain viable until the process of reproduction. Accordingly, the failure of a degraded microbiome to interact with the developing gut of the neonate leads to failure of this partition in the adult: to low faecal energy excretion, excessive fat storage, and concomitant problems with the immune system. Similarly, a weakened gut–brain axis distorts interoceptive input to the brain, increasing the risk of psychiatric diseases such as autism. These effects account for David Barker’s 1990 suggestion of “the fetal and infant origins of adult disease”, including schizophrenia, and David Strachan’s 1989 observation of childhood immune system diseases, such as hay fever and asthma. The industrialisation of modern life is increasing the intensity and scale of these physical and psychiatric diseases and it seems likely that subclinical heavy metal poisoning of the microbiome contributes to these problems. Finally, the recent observation of Harald Brüssow, that reported intestinal bacterial composition does not adequately reflect the patterns of disease, would be accounted for if microbial eukaryotes were the key determinant of microbiome effectiveness. In this view, the relative success of “probiotic” bacteria is due to their temporary immune system activation of the gut–brain axis, in turn suggesting a potential mechanism for the placebo effect.

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.

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.

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.

Forty-three minutes till my shift is over. I log my charts for the day and begin signing them off. It has been a long ED shift; 33 patients and counting. I glance at the main screen and see a 53-year-old woman with a chief complaint of “not feeling well.” My attending's patient list is long with five in the hole, and he just came on shift; I might as well see one more to help out the night float. I assume “not feeling well” will be a quick discharge. It will probably be viral syndrome, and then I can finally get some rest after working four shifts in a row. As I approach the room, I see the curtain half closed and the patient trying to tie the back of her gown. I'm tempted to tell her she can get dressed and I'll do a quick physical examination and save her time. But this time is different. I make eye contact and see a patient who looks like she needs help, not just clinically but emotionally. I introduce myself and begin taking a history. My patient tells me she just doesn't feel well and would like a checkup. During the physical examination, I notice she is in incredible health. She is not obese, her examination reveals no abnormalities, she is well groomed and well nourished, and she clearly takes care of herself. She denies fever, chills, nausea, vomiting, diarrhea, and pain, and the examination findings are normal. Now I'm perplexed. She is not a drug-seeker. She is not requesting antibiotics for some phantom illness. Usually I will tell a patient like this that she's fine and can go home, and even congratulate her on having such a quick ED visit. But this time, something inside tells me to dig deeper. “Ms. Jones,” I say, “why are you really here?” Her answer is unexpected. An emotional Ms. Jones begins to tell me how 2 years ago she stopped taking her HIV medication because she didn't see the point in living a long life. About 5 years earlier, she had been raped, and the rapist had given her the virus. She has no immediate family, though she has a good support network of friends from church. Along the way, though, she has become depressed and feels she has nowhere to turn. I pull a stool over and sit down, and she sees I'm ready to listen. Her story is one of shame, confusion, and loneliness. She fears she is different and has no purpose. I tell her there is no reason to feel ashamed for what happened to her. There is nothing she could have ever done to be the victim of such a heinous act. She should be proud of herself for what she has overcome and endured. She smiles, agrees, and seems somewhat comforted in her moment of despair. She begins to tell me she has not told anyone she has HIV until now. I'm shocked she has kept this hidden for so long; I can only imagine how difficult it is to hold something like that inside. We continue to talk about her ups and downs and the importance of getting into a support group. As we talk and even laugh, I glance at the clock and I see I'm 45 minutes past my shift. Ms. Jones looks better and happier since that hour started. Not forgetting that this is still an ED visit, I counsel my patient that she needs to see an infectious-disease specialist to be reevaluated and to start her HIV regimen. She is now beginning to realize she has a long and fruitful life ahead of her. I tell her what a pleasure it was speaking with her and that she has no reason to live in fear anymore. She cries one last time and I give her a hug—not a hug of pity but one of love and compassion, a hug that tells my patient I understand and care. I hustle back to my computer and complete a fast-track discharge. I am technically overtime at this point, but I don't log it as I feel it would cheat the human interaction I just had. For once, no massive workup, no pain medication, no antibiotic, no late night consult—and yet my patient feels better. And so do I. On the drive home, I contemplate the interaction I just had and think about the role of providers in healthcare. At times I rush the human component of healthcare. Sometimes I forget the esteem that our patients have for us. Sometimes I forget that some patients are looking not just for a clinical answer but for a human connection, and maybe life lessons as well. Sometimes I forget that simply talking to a patient with a humble heart is practicing the best medicine. Reflecting on our bedside manner is critical in providing the best patient care. Yes, it gets busy and there is virtually no time for conversation, but when you have a patient encounter that tugs at your emotions, take the time to explore it. These reflections provide the reminder we all need of why we went into medicine in the first place.Box 1

How does context affect student writing? The author suggests that problem-based learning can provide a meaningful context for students to develop, understand, and rehearse writing skills.

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Wavelength-division-multiplexing (WDM) is the rapidly-evolving solution to increased fiber bandwidth and enhanced network connectivity through the existence of many networks in parallel on a single fiber backbone. Wavelength can be used merely to upgrade fiber capacity or to provide independently configured subnetworks over a single fiber platform if wavelength is used for routing. Maintenance of WDM signal intensities over a narrow enough power spread is an urgent area of research not adequately addressed in the fast-paced deployment and WDM upgrade agenda of many service providers. Current EDFAs are not flat across anything near the 32×0.4 nm channel range anticipated for very dense WDM networks. Even evolving flattened amplifiers will not equalize channels which, due to component or source variations, have significant and progressive attenuation relative to other channels.