Improving preparations for gastrointestinal surgery

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Published: 21 Sep 2017
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Dr John Alverdy - University of Chicago, Chicago, USA

Dr John Alverdy talks to ecancer at the Microbiome in Cancer and Beyond 2017 meeting about how the gut microbiome influences infectious related complications after surgery. It has become more clear in recent years that certain microbes of the microbiome play an important role in recovery after surgery, and antibiotics which destroy everything could actually be limiting this process.

The issue is how to determine which microbes to target, this is particularly difficult when the composition of the microbiome is so varied and diverse within, and between, individuals. Dr Alverdy is hoping for more parsimonious and rapid diagnostics to understand the composition of the microbiome right before an intervention; it is simply a matter of time before this technology becomes available.

For now, he aspires towards a self-coined 'Bowel Prep 2.0', since previous preparation methods have not been properly studied. Methods such as eating a plant based diet, taking probiotics, and not eating before surgery, haven't yet had thorough biological and statistical analysis. He also emphasises that we should use our modern-day analytical resources to deduce a more targeted preparation for gut surgery.

He concludes that the recovering microbiome must be monitored to understand the composition at the inflection point which dictates either the recovery, or downfall, of gut health. 

We’re very interested in the role of the microbiome in predicting and influencing infectious related complications after surgery which include both wound infections, extra-intestinal infections such as pneumonias, sepsis, blood infections and a problem called anastomotic leak which is when you remove a segment of the intestine and then resew that segment back together why that segment sometimes doesn’t heal and actually leaks. It’s like a perforated appendix or an ulcer, it leads to spillage of the toxic luminal contents which can cause a severe infection and even rarely death.

Why is it key to look at this?

We went from a period of understanding that gut microbes play a strong influential role in why people who develop infectious complications after surgery develop sepsis and die. This began in the early 1900s when infection rates after colon surgery were extremely high – you were cutting across this organ full of bacteria and, my gosh, you’re going to spill some of those contents. If that connection leaks we had very few antibiotics back then and the death rate was quite high. We have developed antibiotic regimens over the last 50-75 years that make attempts to kill as much as we can so that those infectious complications are reduced significantly.

But we’ve then come to realise that, gee, maybe there ought to be some selectivity in what we kill and what we preserve because there’s this evolving body of knowledge suggesting that certain elements within the microbiome actually drive a recovery response. So gee, let’s target therapy, let’s kill the things that are the bad actors and preserve the things that are the beneficial or good actors but we need to know how to discriminate between each of those and therein lies the ruse, therein lies the problem. How do you measure that and how do you measure it in real time and how do you measure that in individual patients? Because the data are so robust you get terabytes of data back when you start sequencing the microbiome that you need to be able to understand what you’re looking at.

How can we begin to look at such a complex microbiome?

What we need are more parsimonious and quicker turnaround time point of care diagnostics which means that you can actually measure something right at the point that you’re caring for the patient and get the result back quickly. Right now there is no methodology for that so we tend to take snapshots that take weeks to months before the data come back and they’re not useful to intervene in the patients. But there are several efforts around the world to be able to deliver that promising technology and once that happens we’ll know better what we’re doing.

How are approaches for large-scale interventions, like surgery, changing?

I have written and maybe I’ve coined the term Bowel Prep 2.0. So we prepare the bowel for surgery, we’ve been doing it the same way for fifty years, where we have patients drink a solution that cleans out the intestine then we give them oral and IV antibiotics and it’s worked quite well. But that’s called the bowel prep or the bowel preparation and we need Bowel Prep 2.0. So what body of knowledge will inform the design of Bowel Prep 2.0? For example, should a patient maybe eat a plant-based diet for two weeks? Basically I think you should drink smoothies for two weeks. Well, do you need to do it for two weeks, can I do it for two days? I don’t know. How about a week? I’ll try it 24 hours. That’s one aspect. Will that make a difference? You have to add the intervention in macro and measure the response to know if that’s meaningful.

The second thing would be most patients today have nothing to eat or drink after midnight the night before surgery. Is that a good idea? Is that short-term starvation a good idea? Yes, well I’ve been doing it for 20-30 years, haven’t had a problem. Well, I have a problem every now and then but that’s the patient, they were old. Surgeons have a lot of explanations, they have very few answers at the molecular level. So it’s now time to move from that’s how I explain away that complication to this is how I’ve analysed that complication. In order to do that at the macro level practice has to change. We actually have to say eating highly processed foods and being obese and then having a big operation not a good idea. How can we fix that? Maybe somebody ought to decide whether just ten pounds of weight loss on a low fat, maybe plant-based diet for a week or two or three matters. Nobody knows.

Then the second thing would be are there things that we can drink right before surgery, probiotic solutions, other things, that might bolster the resilience of our microbiome through the process of surgery. Three, can we get away if we did that with less antibiotics or maybe more focussed antibiotic treatment to preserve the good guys and supress or kill the bad actors?

Then the fourth thing that we’re working on is are there ways to contain the harmfulness of bacteria without killing them. These are called antivirulence therapies, they’re therapies that target the expression of harmful products that bacteria make without just killing populations of them. That seems to be very promising and we have several compounds that we’ve developed in my laboratory aimed at that.

So the macro is the practice of medicine and surgery will change because microbiome science allows us to analyse data and display it in a meaningful way where patterns can be recognised and practice can be changed. But I made the point in my lecture of empiricism ad absurdum which is ‘Let’s try this and see what happens!’ Aren’t we past that? It’s 2017, shouldn’t we deliver a little more personalised, individualised medicine that exploits our ability to analyse at the molecular level? Yes.

How long does it take the microbiome to recover after surgery?

We don’t know because it’s never been studied so I call this refaunation. Like if you remember back at the turn of the century when farmers couldn’t figure out why their crops were dying so they slashed and burned, they cut everything down and burned the fields and then things refaunated, perhaps because they killed beetles or fungi or gosh knows what they killed. We need to determine what that rate of refaunation is and what the composition, membership, community structure and function of the refaunation to determine what is the tipping point at which this level of microbiome drives healthy recovery and that tipping point at which this level of a microbiome impairs healthy recovery. We don’t know that inflection point but it’s fundamentally going to be deterministic of outcome and it’s fundamentally solvable or measurable.