Health in the time of artificial intelligence___Being healthy with AI tools

Health, its Hallmarks and AI

According to the World Health Organisation (1948), health is:

"a state of complete physical, mental and social well-being and not merely the absence of disease and infirmity".

But the meaning of health has evolved over time, so this year two biologists Carlos López Otínand (Professor of Biochemistry and Molecular Biology at the University of Oviedo, Spain) and Guido Kroemer (Professor of the Faculty of Medicine of Paris Descartes University) have decided to define health as:

"the presence of the Hallmarks of Health".

In their paper, published in Cell on January 7th 2021, they are telling us that:

“health resides in the overall organisation of the meta-organism that integrates the host and the microbiota”.

Let’s see now the hallmarks of health by Carlos and Guido and some AI tolls that can help us stay healthy.

Hallmark 1: Integrity of Barriers
We exist only because we have barriers (i.e. the intestinal, respiratory and cutaneous barrier) that shield us from our environment, and because we have subcellular, cellular and inter-cellular compartments, that they are allowing the formation of electrophysiological and chemical gradients at the level of organelles (i.e. mitochondria and nuclei), cell membranes and internal barriers (i.e. blood-brain).

It is this compartmentalisation in every living organism, a consequence of the reduction of entropy (the amount of entropy is a measure of the molecular disorder, or randomness, of a system), that is actually allowing the maintenance of health.

Your skin for example, it is not only the largest organ of your body, but it has many roles that are essential for your health:

is protecting you from physical/chemical damage, pathogenic microbes and excessive water loss (both keratin and glycolipids are hydrophobic, making the stratum corneum the outer layer of your epidermis waterproof, that prevents dehydration);

is providing you thermal regulation (the blood vessels of the dermis provide nutrients to the skin and help regulate body temperature);

is absorbing specific ultraviolet wavelengths for your vitamin D synthesis;

is playing a critical role in sensory perception and immune surveillance (the skin provides the first line of defence, and primary immune surveillance incorporates the mechanisms for bringing environmental antigens that are encountered in the skin, antigen-presenting cells/APCs and naive T cells in the skin-draining lymph nodes), and

is hosting friendly bacterial species that provide health benefits by boosting skin’s barrier function (in total, you have on average 1.8 m2 of skin and more than 1.5 trillion bacteria that live on it/ Skin flora).

Any alterations or deficiencies in the structural and/or regulatory components of the network just described, can cause severe skin pathologies.

So, it is not a surprise that Google has an AI-powered dermatology tool that is a web-based application (still to launch), to figure out what might be going on with your skin. By simply using your phone’s camera you take three images of your skin (hair or nail concern) from different angles, and then you are asked questions about your skin type and other symptoms. Then, the AI model analyses all information you provide and draws from its knowledge of 288 conditions to give you a list of possible matching conditions that you can then research further.

Regarding now the skin microbiome, that has a large reservoir of metabolic enzymes which can metabolise molecules (such as cosmetics, medicines, pollutants, eventually forming the skin exposome), a curated database of metabolic enzymes (1,094,153), reactions and substrates from ∼900 bacterial species from 19 different skin sites was used to develop “SkinBug".

SkinBug is an AI/ML-based tool used to predict metabolism of molecules from the skin microbiome and displays a multiclass multilabel accuracy of up to 82.4% and binary accuracy of up to 90.0%. In particular, SkinBug predicts all possible metabolic reactions, associated enzymes, reaction centers, skin microbiome species harboring specific enzymes and the respective skin sites, and this can find applications in exposome and microbiome studies in dermatology and in skin cancer research.

And since we are already meta-travelling, Facebook's new parent company Meta, has just revealed a new AI-powered system that helps robots recognise and react to tactile sensations. In other words, future robots might have synthetic skin that helps them “feel” — to better grab items and navigate!

Another big barrier, is the intestines, for example your small intestine is so surprisingly long that if you unraveled and spread it out, it would cover a tennis court (source). The intestines together with their microbes are sometimes called your 'second brain', and they form your gut microbiome—made up of trillions of bacteria, fungi and other microbes—that play a very important role in your health, like:

controlling digestion (for example bacteria residing in the large intestine play an important role in digestion of dietary fibre to yield short-chain fatty acids, or SCFA, such as acetate, propionate, and butyrate. In particular, patients with mild cognitive impairment, dementia, and Alzheimer’s disease often have reduced levels of SCFAs. A natural compound that mimics SCFAs is fenchol, that gives basil its characteristic scent!!!)

benefiting your immune system (by regulating immune homeostasis),

protecting against pathogens (studies describe how resident good microbiota appear to outcompete unwelcome visitors) and

hosting nutrient, xenobiotic and drug metabolism (for example, the gut microbiota can affect the efficacy and toxicity of chemotherapy, radiotherapy and immunotherapy).

Accordingly, a great effort is being made to study the gut microbiome with the help of AI.

Surprisingly, even though we are already space travelling, modern-day scientists have difficulties studying the around 500-1000 different species among the approximately 100 billion active bacteria living in your intestines. Therefore, researchers at the University of Copenhagen have developed an AI method to map all the intestinal bacteria using faeces.

For example, one gram of faeces contains around a billion bacteria of 500-1000 different kinds, and by reconstructing their DNA and feeding with this data the AI system, researchers will have an idea of the types of bacteria they are dealing with, what they are capable of and what they actually do. Is yet difficult to make predictions, but probably in a near future we will have an AI toilet analysing our gut microbiome in poop, and telling us if something is wrong with our immune system or even our mental health. In fact, studies have shown that our gut microbiome might also play a role in neurological conditions such as autism, epilepsy and depression, by interacting with our nervous system and even releasing molecules that can perhaps make their way to the brain.

Hallmark 2: Containment of Local Perturbations
Your skin barrier, that accounts for about 15% of your body weight, is constantly subjected to “perturbations” that can derive from "accidental and innate events" like incomplete and asymmetric cellular division (failed DNA repair and accumulation of dysfunctional organelles or proteins), and from "accidental external events" including invading pathogens, chemical or physical trauma.

All these “skin perturbations” just mentioned, can compromise your skin barrier, therefore it is essential to confine them in order to maintain a “healthy state”, avoiding them to spread to a systemic level.

For instance a trauma, such a burn in your skin, normally gives rise to a rapid wound healing response designed to repair the trauma, activating local inflammation function, capillary angiogenesis and activating proliferation of fibroblasts and epithelial cells (barrier healing).

When the wound healing capacity is reduced, as it occurs in the elderly or with patients with diabetes or hypertension, this increases the susceptibility to chronic and systemic complications.

As a matter of fact, wound care is a very attractive area for AI, since the cost of chronic wound management (i.e. skin ulcers) was 5.4 billion pounds in UK, and that’s about 5% of the British national healthcare spending.

Accordingly, companies like Swift Medical (the global leader in digital wound care), Tissue Analytics (an iOS and Android platform app that simplifies wound tracking and documentation) and Healthy.io (a company that uses computer vision and ML to transform smartphone cameras into clinical grade medical devices) are all building systems for taking a short video of a wound—rather than a still image—and then computer algorithms can actually make a 3D measurement, allowing them to automatically measure length, width, surface area and even depth. This would allow to follow patients' wound healing response remotely.

Hallmark 3: Recycling and Turnover
But apart the maintenance of the barriers and the confinement of any kind of perturbations, all of your cellular/subcellular components must undergo modifications due to endogenous damage (i.e. oxidation), so most cell types and their cellular components must be constantly recycled and replaced without errors.

For example, the keratinocytes (primary type of cell in the epidermis) located at the surface of your skin undergo desquamation, and they are replaced with proliferating cells in the basal level that move upward while going through terminal differentiation and keratinisation (Cell Death, Removal, and Replacement).

Let's see how AI can help here.

Researchers from Tokyo Medical and Dental University (TMDU) reported, in a study published in February 2021 in Stem Cells, that their AI system, called DeepACT, can identify healthy, productive skin stem cells with the same accuracy that a human can. This is very important, because keratinocyte (skin) stem cells are used to treat inherited skin diseases and to grow sheets of skin that is used to repair large burns.

Let’s move now to the meta-organism and its ability to be healthy.

Hallmark 4: Integration of Circuitries
All multicellular organisms are “meta-organisms”, integrating the host and the microbiota (bacteria, archaea, fungi, phages, viruses and parasites) that inhabit in them.

Just to put in perspective, the human meta-organism consists of 30 trillion of human cells (200 or more types of cells from the 80 known organs), while the human microbiome is estimated at 39 trillion of microbial cells including bacteria, viruses and fungi that live on and in humans. As a matter of fact, we have around 20-25,000 genes in each of our cells, but the human microbiome potentially holds 500 times more.

Interestingly, all these trillions of cells, from host and microbiota, build in a way that facilitate the integration of their circuitries (Intracellular Circuitries, Inside-Outside Communication and Outside-Inside Communication), within and between the different layers of each meta-organism, in order to maintain the stability of the whole system all the time. Just imagine the number of connections and interactions between these trillions of cells!

Consequently to these mosaic eukaryote-prokaryote meta-interactions, your gut’s microbiota for example not only influences digestion and absorption of nutrients, local synthesis of vitamins, gut motility, clearance of pathogens, elimination of xenobiotics, inflammation and colon carcinogenesis, but exerts also long-distance effects via neuroendocrine circuitries, to prevent overt inflammation, autoimmunity, allergy and oncogenesis.

In fact, it is not a surprise that diseases like cardio-metabolic disorders, cancer and even psychiatric conditions have all been linked to “modifications” in the composition of the gut microbiota (dysbiosis of the gut).

Let's see now the surprisingly link between high blood pressure, depression and gut bacteria, analysed with the help of AI.

Researchers at the University of Florida Health have found (2019) that the gut microbiome affects the physiology and molecular events at parts of the brain that control both blood pressure and depression. And only now (2021) they have have found, using ML, that one specific bacteria is suspected of causing depression coupled with high blood pressure. Their findings were published recently in the American Heart Journal.

For this reason, apps and sensors controlling your gut health are in great demand right now.

For example, the new Atlas app, by Atlas Biomed a UK-based personalised health company, is the world's first AI-based food tracking app for gut microbiome, with a photo-based food tracking system combined with microbiome test results set to revolutionise preventative healthcare. Since, most of the consumers haven't got a clue as to how many grams of fibre they're taking in on a typical day, the Atlas app is set to address this growing problem, by improving in this way their gut health.

Keep in mind, that the American Heart Association Eating Plan suggests eating a variety of food fiber sources, with total dietary fiber taking 25 to 30 grams per day from food, and the top-fiber foods are: Beans, Lentils, Broccoli, Berries, Avocados, Popcorn, Whole Grains, Apples and Dried Fruits.

Hallmark 5: Rhythmic Oscillations
Moreover, the timing and the precise order of all molecular and cellular events inside us, are essential for life, for maintenance of health, and determined by the:

ultradian oscillations (with a periodicity shorter than 24 h),

circadian oscillations (the evolutionarily conserved and most studied circadian clocks or internal primary master-body clocks, form a self sustaining negative feedback loop which is now thought to form the driving oscillation of our 24h timing system), and

infradian oscillations (with a periodicity well above 1 day),

that all provide rhythmicity to all our physiological functions.

Any alterations of our utradian, infradian and circadian rhythms are associated with an increased risk of pathologies ranging from cancer and depression, to diabetes and dysbiosis. For example, not sleeping enough, coupled with non-salutary dietary habits and eating schedules can disturb the alignment of the feeding-fasting cycles to the circadian cycle and cause metabolic perturbations.

Moreover, poor sleep quality has been associated with stress, anxiety, smoking, sugary drink consumption, financial concerns, workplace pressures, regularity of working hours, physical activity and commuting times. As a result, sleep deprivation and alterations of our utradian, infradian and circadian rhythms, is kind of a (silent) epidemic nowadays compromising our health.

Let's see now how you can check your circadian rythms (and quality of sleep) with AI.

Smartwatches and activity bands (Fitbit, Garmin, Misfit, Polar, Samsung, Withings and Mio Fuse), under-the-mattress tracking pads (Beddit and Withings) and mobile phones offer a wide range of sensors (such as wrist device for quantifying movement patterns, for heart rate, gyroscopes, microphones etc) to monitor sleep patterns. For instance, a device known as iSleep leverages a smartphone’s built-in microphone to detect events, such as body movement, cough and snoring that happen during sleep, by processing the acoustic signals. And just this year, Nanowear, a hospital-at-home and remote diagnostic platform that used proprietary wearable cloth nanotechnology sensors and AI, received its third FDA 510(k) clearance, that enables Nanowear to implement AI and deep learning algorithms that will inform remote diagnoses as software-as-a-medical device (SaMD). The company is also working on FDA clearances for its software to diagnose or monitor hypertension, chronic bronchitis, sleep apnea, worsening heart failure and post-surgical recovery. In the end, by monitoring your sleep and by collecting your sleep data all these devices can help you monitor also your health status.

Hallmark 6: Homeostatic Resilience
Health is also about maintaining myriads of other biological parameters such as:

blood pH,

serum osmolarity,

arterial oxygen and carbon dioxide,

glycaemia,

blood pressure,

body temperature,

body weight, or

the concentrations of hormones

at homeostatic resilience, which is close to a constant level. This homeostatic resilience involves genetic, neural, metabolic, immunological and microbiome-based mechanisms, and now can be monitored in order to stay healthy.

For example, the hypertension health-tech firm Aktiia has Aktiia's Optical Blood Pressure Monitoring (OBPMTM) that algorithms leverage optical sensors worn on the wrist and provide blood pressure values using photoplethysmography, in order to analyse the changing diameter of the arteries occurring at each heartbeat. This optical measurement is done automatically, so users are not aware and stressed, and do not have to interrupt their day or their sleep to take a measurement.

Moreover, a new report is now claiming that Apple has started working on expanding Apple Watch-like health monitoring to its AirPods lineup. In particular, future AirPods could get posture monitoring and body temperature sensing! Finally, the new Galaxy Watch 4 has a sensor that can measure skeletal muscle mass, basal metabolic rate, body water and fat percentage of the body and it is the world's first smart wearable to run advanced Wear OS, developed jointly by Google and Samsung engineers.

Hallmark 7: Hormetic Regulation
Let's talk about hormesis now.

Hormesis—namely low doses of toxins elicit a protective response that prevent the organism from experiencing harm on exposure to a higher dose of the same toxins—is the 7th health hallmark also affecting your health.

For example, a mild/transient mitochondrial stress (exercise, caloric restriction, intermittent fasting and dietary phytochemicals) can induce beneficial responses in the brain, by causing the production of low levels of mitochondrial oxidants (ROS) that promote the expression of protective genes in neurons, safeguarding them against more severe oxidative stress, while diminishing the risk of oxidative and ischemic injuries.

For all the above reasons, the intermittent fasting trend is on the rise, and it is not a surprise that the first page of Google is dominated by articles like: "10 Best Apps For Intermittent Fasting In 2021" or "7 Best Apps for Intermittent Fasting 2021" or "8 Best Intermittent Fasting Apps That You Must Try in 2021" etc.

Take for example, Simple, the developer of the popular intermittent fasting app, has an AI-based feature which will enable the app users to create their own fasting strategies and let them achieve their goals more efficiently. Their AI tool analyses the behaviour of the user and provides personalised guidance, based on every users' personal goals and data. Simple is one of the leading app developers in the field of intermittent fasting and is available on both iOS and Android platforms.

Hallmark 8: Repair and Regeneration
Finally, in contrast to cell turnover (3rd hallmark) that occurs without specific stimulation, repair and regeneration are stimulated responses that occur in response to a precise type of damage inflicted to the system.

In particular, cells have developed intricate signalling networks like DNA Damage and Repair, Protein Damage and Proteostasis, ER/Mitochondrial/ Lysosomal Stress Responses, Tissue-Level Regeneration and Cell Identity Reprogramming that systematically sense and react to specific types of damage in all strata of the body.

Regenerative medicine is a branch of biomedical sciences for restoring the structure and function of damaged tissues and organs, and involves the usage of stem cells, immunomodulation, tissue engineering therapies, 3D bioprinting techniques and the adoption of AI in the production of regenerative medicines. They hold potential for the treatment of various chronic diseases, such as Alzheimer's, Parkinson's and cardiovascular disorders, osteoporosis and spinal cord injuries.

On October 26, 2021, Singular Health has been awarded funding to undertake a collaborative research project focused on developing an AI-based tool, integrated into Singular Health’s Surgical Planning software for editing and review, to automatically 3D design replacement cranial implants. This tool uses AI to analyse the unique shape of a patient’s cranium from CT scans, enabling the creation of patient-specific cranial implant model for 3D printing.

In the end, health is a state of perfect balance between many, if not all, the above hallmarks and your ability to bounce back from adversity, in a highly interconnected world where eukaryotic and prokaryotic cells have learned to co-exist billions of years ago, giving us eventually us humans.

Thank you for reading 💙

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