Salvation in a yoghurt – Does your gut microbiota hold the secrets to good health?

Based on a talk by the same name given by Dr Gareth Parkes – Consultant Gastroenterologist @ the RCP Update, AMEX Stadium, 2019 – 20/03/2019

Our GI Microbiotic Makeup

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Élie Metchnikoff won the nobel prize in 1908 for his discoveries about bacteria and immunology. After this he developed the theory that aging is caused by the build up of toxins in thegut. In an attempt to live forever he drank sour milk (Bulgarian Kaffir Yoghurt) every day. Unfortunately it didn’t work and he died at the age of 71 and was buried in Paris. 

He however, is the great grandfather of this field and set about a chain reaction which leads up till today. In the 1990’s to early 2000’s we discovered that we are outnumbered 10 to 1 by our bacteria, but now what we have discovered & what a lot of people still don’t know is t

hat both our cells and the bacteria are probably outnumbered by the viruses harbored within the bacteria.

"Rotavirus"

It is not yet clear what the role of these viruses are but the process of discovery so far has been much like zooming in on a google map of the Amazon. To continue the analogy we used to only be able to see the broad view of the microbiome & are only now zooming in on the roots:

Amazon Rainforest Map

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Initially we could only culture the bacteria in a petri dish. Then we developed complex immunoflourescence assays. Now we have developed methods to look at the metabolome & transcriptome to assess the immune processes going on within the bacteria. It’s not just about the bacteria you produce, but also about what is going on inside them. We are only just starting to understand the impacts of this. The next stage will be looking at the virome and it’s implications.

The impacts of these processes are truly profound and affect your neurophysiology, neurohormonal functioning and cause some disease. Let’s take a look at how this has developed over time.

Your Microbiotia & Inflammatory Bowel Disease?

One of the earliest avenues for research exploration was ? E.Coli in macrophages – could this cause Crohn’s? After lots of research it was discovered that they didn’t.

The Microbiome Diet - Healing the gut naturallySubsequent studies looking at bowel trauma and healing discovered that by re-biopsying previously biopsied colon it was possible to quantify the immunological response. In Crohn’s the healing response was subdued, unlike in UC patients or healthy controls. A similar response was found by injecting E.Coli into the arm. Healthy controls had a big peak in response, but in Crohn’s the response was subdued.

There Are More Unique Species on Earth that We Thought ...

Then several studies came out showing that the microbiota themselves become less diverse in UC/Crohn’s. This is pattern that continues throughout health – disease on a spectrum. You have low-risk individuals at one end with intact mucosal barriers, at-risk patients with perhaps a ‘leaky gut’ and other patients with Crohn’s/UC disease and complete mucosal failure asosciated with decrease in microbiomal diversity.

Other researchers have looked at whether fast food is causing the gut to become leaky? Transfats and inflammatory fats appear to disrupt this barrier and lead to dysbiosis. Dysbiosis subsequently predicts disease and biomarkers exist which can be used to map and anticipate this process to some degree.

FDA on trans fat: Halt use in U.S. food within 3 years - CNNWe have also found that in general a poor diet high in trans-fats can completely disrupt the baseline immunological state, leading to raised level of pro-inflammatory cytokines, increased baseline inflammatory response and higher risk for immune-mediated disease. This has particularly been demonstrated with high trans-fats in mice models.

But how does this apply to humans and what can we do to treat these diseases?

Modulation – Probioitic

An analogy. Imagine a football stadium like this one this talk is being delivered in and the grass is your microbiome.

Pre-biotics are like fertilizer the grass while pro-biotics are like the new grass seeds.

BIMUNO - PREbiotics for Anxiety, OCD, Depression & Overall ...

Pre-biotics include dietary influences. There is good evidence that pre-biotics & dietary changes can be effective for IBS and possibly UC, but not so much in Crohn’s.

Regarding probiotics, their origin is steeped in history. In 1917 during the first world war one particular German trench crew got dysentery. All of them died except one individual. His microbiome was cultured and grew an organism – E.Coli Nissile which appears to confer some protection to E.Coli:

Immune modulation by E. coli Nissle 1917. The probiotic E ...

Following on from this over the years many new probiotics have been created, but only few have actually developed good evidence to support them. Recently the rules have changed and without this evidence they cannot be labelled as probiotics – sorry Yakult.

Several studies have more recently followed:

  • Lactobacillus study – showed no improvement in the ability to metabolise alcohol.
  • Bifidobacterial cultures in Japan – small reduction in visceral fat
  • L.casei – Failed to improve immune responses to vaccination in healthy volunteers
  • Nematodes have been made to live longer by probiotics
  • Sad but not depressed people can possibly be helped by probiotics
  • Rotavirus infections can definitely be shortened by the use of probiotics
  • CD studies have shown no benefit for maintainence of remission
  • In UC – VSL#3 trials showed some benefit. This definitely works in chronic pouchitis and was the first probiotic to be NICE approved.

VSL#3 Probiotic Review - The BJJ Caveman

Modulation – Faecal Microbiota Transplant (FMT)

If probiotics are the seeds, FMT is when you lay down entirely new turf!

Historical attempts have included the Japanese drinking ‘Yellow soup’ and the Berbers eating camel dung.

There are several successful studies, showing:

  • FMT transplant in mice can make obese ones slim!
  • In C-Difficile it categorically works. So much so, that the landmark study had to be stopped early at 43 out of 102  patients planned to be recruited. Diversity of the microbiome was also shown to improve.
  • FMT doesn’t work in IBS – placebo is perhaps even better!
  • Obesity – Vrieze et al 2012 demonstrated a 75% increase in insulin sensitivity using FMT, but further research is needed about the generalisability of this result.
  • UC perhaps beneficial. Further trials are ongoing.

C. difficile infection and the role of faecal microbiota ...

Panel interview with senior members of some prominent healthcare AI startups #GiantHealthEvent

Data Science representatives from Eagle Genomics, Babylon Health, Touch Surgery, Myrecovery, Creation were interviewed by Cognition X.

All these companies use machine learning in different ways either to analyse the genome, diagnostic/surgical implications or helping patients directly.

All of the panel agree that AI is coming back after going through a ‘nuclear’ winter.

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Eagle Genomics feel that by 2025 there will be over 250 million patients with their genomes sequenced. This constitutes several zetabytes of data. This cannot be analysed by humans but only machines. We have a burgeoning data management crisis that can be solved in no other way. We need to turn big data into actionable insights.

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Babylon health say they want to make healthcare affordable to all – that is their vision. They believe in augmenting doctors and making them safer. Babylon feel the biggest need is in Africa. That is why they are working in Rwanda because the needs are so great.

They think that in the next 5 years there needs to be some sort of regulatory mechanism to govern the use of AI diagnostics. They want to improve the productivity of doctors not replace them.

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Touch surgery feel that humans alone cannot deal with all the data alone. They feel that it is essential to use that data in order to learn how to make their product as good as they can. Currently they are trying to use machine learning to improve the user experience and training. They believe that the technology should also help the surgeon in the same way that power-assisted steering and GPS enhance the driving experience.

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Myrecovery are analysing how their users are using the apps as well to try and predict their recovery. A lot of people complained about the US election predictions. Garbage in = garbage out. Longer term they see it as a core asset to the business. They feel that the present situation is unsustainable. We can’t compete with robots any more, we need to work with them in order to get the job done.

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Creation feel that it will be essential in the future but at the present are focusing on building data sets and getting them verified by medical professionals. They talked about developing a system that could analyse a photo via a network – like instagram for medical diagnosis. They feel that doctors use social media quite a lot. Sometimes they have found doctors answering individual patients on social media. They feel the barriers are breaking down. They also sited the microbiome. He talked about machine sentiment analysis and how it is currently largely useless. Most ‘AI’ is still heavily dependant on human interaction to make it work but in the future this won’t be the case.

Then Charlie asked the panel what advice they would give to tech startups thinking about working in this field. Their advice was:

  • Get good at selling yourself.
  • You need to be in it for the long haul. (We are in the middle of a revolution).
  • Be prepared to change your business model several times.

GE: New Thinking in the Digital Health Ecosystem: Breaking down the silos #GiantHealthEvent

No company or individual is a silo. The internet has changed everything and it is all now connected

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But what will happen when 50 billion machines become connected? Suddenly the data will show us the flow in the hospital, the results will be highlighted. The computers can detect problems and fix them.

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This is the collision of the physical and analytical, brilliant machines with industrial amounts of data and people interacting with them.

We are heading towards a ‘colossal clash’ between the consumer health technology and clinical healthcare. The two worlds are both merging but also on a collision course with one another.

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We are heading to an age where we want to rate everything. This is a consumerisation of healthcare. It will become the norm to rate your doctor online.

In the future nothing will be redundant. Everything will be rankable and in flux. We are heading towards an outcome driven world.

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This is why GE are creating an open ecosystem cloud to host health applications because there is going to need to be a way to scale innovations quickly. This can provide a portal for developers to test their products quickly and get feedback.

There is no going back. Things are moving fast and GE want to be ready.

The Fourth Industrial Revolution

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Shafi Ahmed then introduced the topic of the ‘fourth’ industrial revolution.

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The blurring of the lines between the physical and digital spheres.

It is about thinking differently in order to solve hard and complex problems. It will involve the interface of medicine, digital technology, societal changes, art and many other things.

It will involve:

Virtual reality

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Big Data / Informatics

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Blockchain, IoT

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Machine Learning / AI

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This is just what we know the fourth revolution will involve. There are many other things as yet undiscovered which will be involved.

The UK’s first ever exponential medicine conference

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Welcome to GIANT

This marks the beginning of a shift in the mindset of health technologists in the UK. There have been other events like the NHS EXPO but their purpose was very different.

This conference as illustrated by the programme is going to be very different.

This is exponential medicine conference, UK.

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The speakers at this conference are not your usual health technology conference speakers. I am currently sitting in the middle of an audience full of outside thinking, border pushers within healthcare. A mixture of professionals from medical, business and technology spheres all in one place.

This is the infancy of a small silicon valley type community for health technology in London but it has none of the glitz and glamour of exponential medicine conference. This has much more the feeling of the first DEF CON in June 1993 (I was not there, I was only a child then but I imagine this is what it was like.

Barry Shrier, the Founder started by introducing the term moonshots. These are radical innovations which lack any immediate method of becoming financially successful but have enormous potential in the future.

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The challenges that face us in healthcare now have never been greater. Therefore, the need for a ‘moonshot’ or more likely many smaller ‘moonshots’ to succeed has equally never been greater.

This is the interface at which they occur:

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Barry then talked about the ongoing impact of the NASA program. It is his conviction that we can achieve enormously big goals and we should set out to achieve them for the good of the world. The vision: “To improve the health and wellbeing of humanity, by supporting entrepreneurs and supping healthtech innovation.” He dedicated his presentation to the late Helen Keller. “Life is either a daring adventure, or it is nothing”. H.Keller

It is the spirit of ‘I can do it’ that will enable us to overcome the enormous challenges that humanity faces.

Liver Imaging for Gastroenterologists

Disclaimer: This article is not intended as medical advice for patients but is for informational purposes only, primarily aimed at clinicians.

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The liver is supplied by multiple vessels and divided into 8 segments.

In the normal liver most of the blood supply comes from the portal vein.

Tumours however tend to be supplied by the arterial supply (more on this later).

Regarding imaging. Ultrasound is great but unfortunately results are not reproducible between different operators.

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Common benign findings include: Cysts

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but sometimes they are not so simple

hyadtidThis one above turned out to be a hyatid cyst (Echinococcosis).

haemangioma

Haemangiomas can be even more difficult to distinguish.

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Focal nodular hyperplasia (above) can be distinguished from hepatomas by using Primavist (came out 2004). This contrast is taken up avidly by healthy hepatocytes and not by cancers.

Diffusion weighed MRI can help to distinguish between small metastases and other lesions, however its effectiveness is limited.

fatty-liver

Above is a fatty liver which makes it very difficult to distinguish the liver parenchyma

hepatitis

This is what acute hepatitis looks like on USS. The liver looks ‘brighter’.

The radiologist can also see vessels such as varices, abdominal collaterals, reversed/blocked portal flow and associated ascites etc.

Cirrhosis can be seen but only at an advanced stage so these imaging modalities are not so useful for the early detection of liver disease. Of CT, USS and MRI – MRI is the best at picking up cirrhosis but it is also the most expensive and difficult to access test.

Hepatocellular Carcinoma

The above conditions are all benign, but what we really want to spot are the cancers. These primary cancers normally occur in those with pre-existing liver disease.

Diagnosis can be very tricky if the timing goes wrong which is why you need a skilled radiology team.

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Above are some images of HCCs. They tend to be surrounded by areas of necrosis as the tumour develops a rim of dead tissue around it.

Treatment options include:

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Sorafenib, TACE, transarterial chemoembolization, resection and transplant

This is where we are now in 2016 but there are many other investigation and treatment options under investigation. So we can now tell what’s probably going on without doing a biopsy, most of the time. There is still significant margin for improvement.

Next up: Liver disease in pregnancy.

More interesting tech at NHS Expo 2016

Lifelight

This is a really cool sensor system that is brilliant ad it is so simple yet massively effective. The founder Lawrence, is a legend and is doing great things via Southamptons catalyst programme. Watch this space! If I had money to invest I would invested in this.

XPERYE

Used by Shafi Ahmed in London this is a neat peice of kit using Google glass to transmit the wearers vision to a computer. The images can then be annotated or altered to be used in teaching etc. With the Google glass version 1 no longer available and a time lag for its successor and at £300/month this is potentially a very nice little training tool in the right context at the moment. It is certainly fun to play with.

PA consulting’s offerings 

PA consulting have introduced these products at the expo. This is a new probe for measuring Barretts oesophagus through the scope. It was next to the cytosponge but for some reason that had disappeared today. Both very promising innovations in my specialty (gastro) for Barrett’s surveillance.

TEDx NHS

TED has finally landed in the NHS. This proves people are gradually catching the vision. Bring it on…!

New tools to market at Expo 2016

Creavo
This beauty could revolutionise the admission of chest pain. It can more accurately diagnose ACS AND unstable angina in just 3 minutes in the ED. It’s currently going through studies to validate it but I can see it being very successful as it’s price point is only around £100k and it could save NHS trusts millions.

Creavomedtech only just formed. Based in Leeds with a strong support structure, good corporate backing and strong technical expertise linked to the university I think this is one to watch!

Early Sense

This platform by early sense could be useful for patients with dementia as a way to monitor them remotely. However, there are lots of cheaper bed alarms. At £3500 a bed I think this products USP is the monitoring rather than anything else.

Vanguard

This is not a new technology but it’s beginning to scale. Portable theatres and endoscopy units could help some hospitals who have capacity issues. This polentally also has a role in major incident management.

Centrihealth

This is a context based health platform. More advanced than a normal EPR (electronic patient record) system. This uses AI to filter the data and produce a useful record. This tool is FANTASTIC, but they have not yet broken into the NHS because their marketing strategy is wrong. It took me ages to get what they are actually doing and I think thats why they are struggling here. THIS IS A PATIENT SAFETY TOOL NOT A ‘CONTEXTUALISATION’ ONE. If you read this then get in contact because I think I can help you.

There are many more innovative solutions here but these ones caught my eye. To see more visit the EXPO website.

Novel Imagers / VR kit

In the last couple of weeks I have been contacted by several people who have designed various gadgets for Medical VR/interaction. They are iridescent imaging, VIZR, D-EYE and Gesturetek. 

First up Iridescent Imaging 

Mitch Downey founded this company to create fantastic small and life-size VR projections.m  see more images here: http://iridescentimaging.com  The technology looks fantastic but as you might expect it isn’t cheap. I can really see how these might be useful for virtual clinics, particularly in specialties where walking in front of the doctor is a key part of the exam: ie. Rheumatology / Neurology. However, a remarkable product needs a great website and this is something that needs a bit of work. 

Then there is D-EYE

This thing looks excellent. It can effectively enable an ophthalmologist to diagnose a child remotely in another country using just their smartphone but more likely it will be a great clinic application. To be honest I want one on my emergency unit as it looks so easy to use but again these things are new and therefore costly. https://www.d-eyecare.com

Next up VIZR

This is more like a clinician assistant (like Google glass) they feel their user interface and information is more up to date. It looks like a smart gadget but as the video on the site demonstrates it is not entirely unobtrusive to the patient looking at the doctor http://www.vizrtech.com

Time will tell whether there will be enough uptake. My feeling is that unfortunately for this device we are still several years away from IoT and the effects of Big Data having their full impact to help this device work. 

Finally we have http://www.gesturetekhealth.com

These guys are doing something a bit different. Trying to get physical controls to work for rehab /those with disabilities. Unfortunately the website is dire which is a shame as they have some really cool products like Irex-an upper and lower extremity training system. 

It looks like they are doing a great work in their niche. 

Note I have just started a medium blog as well and plan to integrate them later so watch this space. 

Telemedicine: Is it the future? 

​What surprises me most about the article below is the so far low uptake of Telemedicine. The applications for this are potentially vast but due to various restrictions particularly surrounding the reluctance of US health insurers to fund such consultations, the general uptake is still low. 

Several companies in the UK are trying to build these primary care alternatives now (Dr Now, Babylon etc) and it would appear that there is public desire for these things. However, they face lots of challenges. 

Firstly patients are offered more comprehensive services in the NHS even if there is a delay to access them; tests are very difficult to organise at home over the Internet; Patients can’t be fully examined and fundamentally there is a major shortage of GPs. This means that capacity is unlikely to ever be able to meet demand in a cost efficient way without adopting alternative models of triage. 
These challenges can all be overcome in time but the fundamental test will be what patients actually want. As physicians we think we know the answer to this question but have we really asked the right questions? 

Link: http://www.wsj.com/articles/how-telemedicine-is-transforming-health-care-1466993402