Written by Eva Hamrud, PhD
December 3, 2020
22 min read
Topic Review: Microbiome
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INTRODUCTION
The human body is teeming with life, with over 100 trillion micro-organisms calling our bodies home. While these critters cover almost every one of our nooks and crannies, they are particularly fond of hanging out in our gut. Collectively called the ‘gut microbiome’, it has captivated not only the scientific community but also the general public eager to jump on board the gut health revolution.
Perhaps one of the biggest supporters of the gut microbiome and its potential health benefits is Bill Gates, who literally brought a jar of poo onstage in Beijing, stating that the ability to deliver microbial products to treat diseases like malnutrition “is as big a breakthrough as anything else we will do in health over the next two decades”.
The Bill and Melinda Gates Foundation is investing millions of dollars into the microbiome field hoping to find the right microbial biotherapy to help both undernourished and obese children live longer, healthier lives. Scientists are starting to understand, however, that our microbiome affects much more than our nutrition, it helps regulates almost every other organ system, dictating an individual’s risk of chronic disease, and exerting profound control over our mood.
While there is no doubt the gut microbiome plays an important role in health and disease, it’s still early days. Some prominent scientists are starting to observe that both commercial and clinical applications of microbiome-science seem to be drastically outpacing the evidence.
So that’s where Metafact can help. We have brought together over 30 experts on gut health and microbiome-science to help you get the facts to understand what you can actually do to support your gut health today. Here’s what we found…
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NUMBERS
Meta-Index
100,000,000,000,000 the number of microbial cells in your gut (yes, that’s 100 trillion)
5,000 Number of different microbial species found in your body
2 The weight in kilograms of microbiota in your gut
$48,000,000,000 Global market for probiotics in 2018
8,943 Number of research papers with ‘Microbiome’ in title on PubMed
143 Number of startups and funds working on Microbiome on AngelList
3,900,000 Number of people in the US who take probiotics regularly
270,000,000 Number of prescriptions in the US for antibiotics
ORIGIN STORY
From ancient China to Californian ‘Raw’ Water
The microbiome revolution is well and truly underway, and while it may feel like a modern discovery, history tells us that we humans have known about our gut bacteria for millennia! The earliest recordings of fermentation (a process involving good bacteria) date back as far as 6000 BC in the Fertile Crescent region, and there is evidence that fermented milk products were consumed as early as 7000 BC. Fast forward several thousand years to fourth century China, and the first faecal microbiome transplant (FMT) was being used to treat diarrhea, albeit with limited success with the “yellow soup” administered orally and likely causing a raft of potentially dangerous complications.
By the mid 17th century, veterinarians were beginning to use faecal products and by World War II, camel poo was being used by German soldiers to treat bacterial dysentery. Today, there are thousands of microbial biotherapies available reflecting our intense curiosity in our microbial friends combined with the clever, and sometimes misleading marketing campaigns of the growing probiotic market.
Perhaps the most absurd example of the probiotic revolution is “raw water” – water that unfiltered, untreated and unsterilised, containing a wealth of microbial life being branded as “probiotics”. Sold at a whopping 36USD, raw water is marketed as the epitome of the hunter gatherer lifestyle, free from “toxins” in tap water that are apparently responsible for the numerous aliments that dominate our modern world. But what this “solution” fails to acknowledge is the our ancestors also died in vast rates from typhoid, cholera, giardia and diarrhoea, and life expectancy was extremely low.
The raw water case study also raises some relevant concerns for other gut health supplements – while it may contain some “good” bacteria, it is also likely to contain bad ones. This is the same case for commercial probiotics, with a study reporting that only 4% of the tested probiotic formulations actually contained what was stated on the label.
Probiotics aside, supporting our gut microbiome is certainly backed by science and an area of intense scientific, medical and personal interest. We are now starting to understand that each and every one of us has a distinctly unique gut microbiome, just like a finger print. And while this might get you excited at the prospect of catching a criminal who leaves a cheeky poo at a crime scene (definitely not backed by science … yet), it is getting the medical community excited about what that means for personalised medicine and disease prediction.
But while we are in the discovery phase, it is difficult to understand if these findings are just hype or hope. This, combined with hasty commercialisation and savvy marketing, makes it almost impossible to decipher fact from fiction. So to help you find your way, we are covering the most popular questions on the microbiome to make sure you are ready to sift through the shit and understand the best way to support your microbiome.
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THE CONSENSUS
Is the microbiome a human organ?
Read the full answers to this question here. One of the most surprising facts about the microbiome is its sheer size, with the average adult colonised with trillions of microscopic life. In fact, there are 1.3x the number of microbial cells than there are human cells and the number of genes in the microbiome outweighs those in the human genome 150:1!
In the human gut alone there are about 2kg of microbial life, and so it isn’t surprising that they have such a profound impact on our nutritional status, mood and cognition and risk of disease. The size of our microbiome combined with its ability to carry out key functions that us mere humans cannot do alone (see consensus report on fibre) has prompted some to question the core definition of the gut microbiome … asking is the microbiome a human organ?
While there are some redeeming features about the microbiome that liken it to an organ, 83% of our experts agreed that it does not satisfy all the criteria of a human organ. The microbiome is not an organ “for the simple fact that it is made up of other organisms!” writes Kate Secombe of the University of Adelaide. “Unlike organs, it is not self-contained and it is highly dynamic in its structure/composition” writes Dr Hannah Wardill of the Supportive Oncology Research Group at SAHMRI. Other experts like Dr Tsveta Malinova of the University of Amsterdam explains that “studies on microbiome show it is crucial for proper human development and health”, going on to suggest that “it would not be surprising if one day scientists qualify it as a new organ”.
Organ or not, the thing we all want to know is what can we do to support our gut microbiome? In what’s the role of fibre and probiotics on our microbiome? We have previously covered both of these topics in individual consensus reports, concluding that probiotics are not necessary for a health microbiome, with dietary fibre a much simpler (and cheaper) way of supporting gut health. This largely reflects the fact that probiotics are very transient in their effects – as confirmed in our Probiotics review.
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THE CONSENSUS
Does our microbiome predict diseases like Parkinsons?
Read the full answers to this question here. Recent understanding of just how unique our gut microbiome is has prompted much investigation into whether it can predict disease and respond to certain drugs or interventions. A group from Israel have pioneered this field, demonstrating that an individual’s response to dietary intervention is dependent on and can be predicted by their unique gut bacteria. They went on to show that giving a diet that was selected and designed based on the individual’s gut microbiome improved results, and actually outperformed the recommendations of a dietician.
What we also know is that people with certain diseases, including extra-intestinal diseases (i.e. those that do not affect the gut) have certain traits in their microbiome composition that differentiate them from a healthy population. This has prompted research into whether we can identify these people, or even predict an individual’s risk of developing that disease by looking at their gut bacteria. In the case of Parkinson’s Disease, while 40% of our experts agreed it is likely that Parkinson’s Disease can be predicted by the gut microbiome, they all emphasised that predicting any disease based on the microbiome must be approached with caution.
As described by Dr Hannah Wardill, “the question of the chicken or the egg really hasn’t been properly addressed, with much of the data remaining associative”. What this means is that while people with Parkinson’s disease have differences in their microbiome, it remains unclear if these are causing the disease (i.e. and can therefore be used to predict it’s development) or if they are simply a consequence of the disease.
As highlighted by Dr Douglas Kell from the University of Manchester, it is also critical to recognise that even if something can be predicted, “the question is with what accuracy (false positives and false negatives, also different types [of Parkinson’s disease], degree of severity, etc)”. This may be less important when diagnosing a disease based on the microbiome, with microbial-diagnostic approaches making up just part of a battery of tests. However, when predicting an individual’s risk of disease in the future (i.e. like 23&Me and emerging at-home poo tests that are on the market), the ethical considerations become infinitely more important.
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THE CONSENSUS
Can take-home microbiome kits predict disease?
Read the full answers to this question here. In recent years there has been an explosion of take-home microbiome startups that allow people to test their microbiome via fecal (poo) analysis. All experts say these kits can’t predict anything just yet – but there is future potential.
“There is much promise in this area, but it’s still in its infancy”, writes Dr Bella Van Sebille from the University of South Australia. Importantly, what this approach fails to account for is the high degree of variability in our microbiome, with the amount and types of bacteria changing in response to numerous stimuli, including stress, diet and medications.
Dr Matt Koci of North Carolina State University explains, “so many factors affect what [these tests] might find in your poo from month to month, day to day, even between breakfast, lunch and dinner.” So how your microbiome looks today is not how it may look tomorrow, which means that, what people can realistically expect to learn from these at-home poo tests is more along the lines of a snapshot of how a person’s microbiome compares to others, and the presence of specific gut infections.
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THE CONSENSUS
Does faecal microbiota transplantation work?
100% Affirmative via 10 experts
Read the full answers to this question here. Faecal microbiome transplantation, or FMT for short, is a process in which poo is collected from a healthy donor and transplanted into a recipient to improve or change the composition of their gut bacteria. Essentially, it is a probiotic on steroids, with a huge amount of good bacteria as well as all their delicious metabolites (waste products) that are extremely important fo gut health.
To many, the process of FMT is not very glamorous, but as demonstrated by the resounding consensus of our experts, it does work… and quite well! But as Dr Edward Deehan from the University of Alberta explains, “it is completely dependent on the disease you are aiming to treat.”
The use of FMT to treat gut infections like Clostridium difficile (Cdiff) has been nothing short of a game changer. Cdiff is a gut infection that costs the US economy over US6billion every year. Usually, it is treated with antibiotics, but it is rapidly becoming resistant, meaning antibiotics aren’t as good at killing this bug as they used to be.
Unlike antibiotics that just wipe out the bacteria in our gut, FMT works by increasing their diversity. These bacteria then outcompete Cdiff for space and food, essentially suffocating it. “[It] is very effective and very safe.” underscores Ian Beales from Norfolk and Norwich University Hospital. “So much so that it is clearly the treatment of choice [for recurrent Cdiff].”
“While FMT is highly effective at treating [Cdiff], with a success rate of at least 90%, it’s efficacy for the treatment of other diseases, such as inflammatory bowel disease and metabolic syndrome, remains less clear.”
“There are also many uncertainties”, explains Dr Javier Santos, gastroenterologist from Hospital Vall d’Hebron. He continues, “donor selection, fecal and recipient preparation, delivery methods and security issues need to be solved before steeping ahead in generalizing FMT therapy.”
In summary, FMT is a promising therapy but not the panacea.
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THE CONSENSUS
Can childhood use of antibiotics trigger allergies later in life?
Read the full answers to this question here. The gut microbiome is highly plastic, meaning it changes in response to a variety of environment factors, including diet, stress, disease and medication. Antibiotics are well described to have a profound impact on the composition of the gut microbiome, depleting many of the good bugs whilst sparing the bad ones. Over the past 15 years, there has been a ~90% increase in the use of antibiotics across the globe. These figures contradict current public health recommendations which urge prescribers to restrict antibiotic use wherever possible. These recommendations come in light of an increasing body of evidence that antibiotics have detrimental effects on the composition of the microbiome, and in some cases, these changes can have long-lasting impacts particularly when given to young children who still have a developing microbiome.
We know that our microbiome is a very strong dictator of our immune system, training it to recognise and respond to dangerous stimulus, and ignore harmless ones (referred to as “immune memory”). This has lead people to question the contribution of antibiotics to allergies, both of which have drastically increased over the past few decades.
Dr Mirco Schmolke, immunologist from the University of Geneva explains, “In a nut shell, allergic responses are overreactions to certain substances… [and is] partially based on a dysregulated T cell balance”. T cells are a type of immune cell that stimulate damaging immune responses, which in an allergic response, are responsible for symptoms such as swelling and breathing difficulties.
Dr Maria Jenmalm from Linkoping University emphasises that while “a recent systemic review and meta-analysis found that early life exposure to antibiotics appears to be related to an increased risk of allergic symptoms of hay fever, eczema and food allergy later in life” reminding readers that “it is important to note that the studies are association studies, making the evidence less certain”.
Similarly, as highlighted by Dr Rebecca Dewey from the University of Nottingham, “individuals diagnosed with IBD were more likely to have been prescribed antibiotics 2-5 years before their diagnosis”; but again, we are unable to draw any causative conclusions.
Animal models have shed light on the causal relationship between antibiotic use and allergy, with germ-free mice (those that have no microbiome) showing that “disruption of the microbiota early in life shapes which immune cells populate barrier sites (e.g. gut)”, as outlined by Dr Timothy Hand, University of Pittsburgh. He goes on to explain that this modulation of the immune system, specifically in the types of cells that populate the gut, is critical in allergy development. He goes on to explain that while it is likely that there is also an element of immune memory, “this has not been directly linked to the development of allergies… so ‘forgetting’ the the microbiome would not make you more prone to make responses against allergens”.
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THE CONSENSUS
The microbiome and the brain
Our gut microbiome is best described for its impact on its local environment, that is the cells lining the inside of our gut and the immune cells that reside there. But, scientists are beginning to understand that our gut microbiome does much, much more, evening controlling mood and how we feel. This has led to the psychobiotic revolution, made famous by John Cryan, a neuroscientist from Ireland who has been instrumental in discovering just how out gut and brain communicate.
As outlined by Dr Hannah Wardill, there is an intimate connection between our gut and brain that we can all grasp. “Take for example when we get nervous or stressed…. many of us need to use the loo. Similarly, people with gastrointestinal diseases like inflammatory bowel disease, often show a higher incidence of psychological disturbance”.
Dr Raquel Abalo, from King Juan Carlos University, cautions that “this is an interesting topic that deserves far more research before we can draw a conclusion. Preclinical studies and several anecdotal reports in patients show that there could be a link between mental health (including depression and anxiety) and dysbiosis [disruption of the microbiome]”. Nonetheless, these findings have prompted many to ask:
Can probiotics improve your mood?
Unfortunately, it appears that while there is certainly a link between microbial health and mood, probiotics may not be the best approach to improve mood. As outlined by Dr Raquel Abalo, “The recent clinical trials do not show clear effects of probiotics intervention over placebo but acknowledge that subtle changes may be induced that are difficult to detect”.
Others speculate the possibility of manipulating the microbiome to improve mood, but highlight that beneficial effects have only been shown in combination with other approaches. Dr Wardill explains, “A recent meta-analysis (a large study of already published data), showed that probiotics were unable to have any benefit for people with depression. However, when administered in conjunction with antidepressants they were shown to provide additional benefits.”
But of course, just like all aspects of the microbiome, there is conflicting evidence with another meta-analysis reporting probiotics had beneficial effects on mood. The reason for these conflicting results… variability in the probiotics used. As highlighted by Kate Secombe, “Probiotics are often made of specific strains of bacteria, which in contrast to faecal microbiome transplants, do not contain the broad diversity and inclusion of bacterial metabolites. This may therefore reduce the effectiveness of a probiotic on changing microbiome composition.” So, perhaps one day in the future, faecal transplant may be a possibly treatment for mood-related disorders.
Lets not forget our other microbiomes!
While this review has strongly focused on the gut microbiome, it is important to highlight that we have many other microbiomes including the skin, oral, vaginal… all of which are critical to support and maintain for optimal health. So next time you take that course of antibiotics, don’t just think about your gut bacteria, but all of your microscopic friends!
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QUICK ANSWERS WITH CONSENSUS
Are probiotics necessary for a healthy microbiome? No. These studies suggest that while probiotics may not significantly alter the microbiota composition in healthy individuals, they support gut health by promoting homeostasis, enhancing immune function, and protecting against pathogens.
Is a high-fibre diet good for the microbiome? Yes definitely. These studies suggest a high-fiber diet is beneficial for the microbiome by increasing beneficial bacteria, enhancing gut microbiota richness and stability, and promoting health.
Do probiotics permanently colonise the gut? No. Some studies suggest probiotics can lead to transient colonization and beneficial effects on gut health, while other studies indicate they do not permanently colonize the gut.
Do probiotics help restore the microbiome after a course of antibiotics? Maybe. Some studies suggest probiotics help restore the microbiome after antibiotics, while other studies indicate they may delay and incompletely reconstitute the gut microbiome.
Does vitamin D impact the microbiome? Uncertain. These studies suggest that vitamin D impacts the microbiome by influencing its composition, diversity, and the balance of beneficial and pathogenic bacteria.
In predicting disease, is the microbiome more accurate than genes? Not yet. These studies suggest that microbiome data can significantly improve the accuracy of disease prediction compared to genetic data.
Is kombucha beneficial for healthy people? Unlikely. These studies suggest kombucha may offer various health benefits, including antimicrobial, antioxidant, anti-inflammatory, and digestive support, but more human clinical trials are needed to confirm these effects.
TOP ANSWER
Can take-home microbiome kits really predict disease?
Matt Koci: An expert from North Carolina State University in Virology, Immunology, Microbiome, Agricultural Biotechnology
Maybe some day, but we’re a long ways off from that. For now these kits are like home genetics tests like 23 and Me, but years behind. The home genetics kits are are still largely more entertainment than really informing health decisions, but as more people contribute and fill out their surveys they are hoping to find predictive power. The home microbiome testing companies are hoping for the same thing. The idea is if they get enough people’s poo, with enough additional health data from, one day they’ll know what to do with that information.
The issue is so many factors affect what they might find in your poo from month to month, day to day, even between breakfast, lunch and dinner. There is so much more noise in one person’s microbiome sample on one random day, so much more than is in the relatively stable human genome that it is going to take a lot longer for these kits to catch up to just what 23 and Me is today.
And for what it’s worth, while I’m skeptical of these kits. I was curious and several months ago was going to give one a try just to see what kind of data they gave out, but before doing so I contacted several colleagues who also work in this area and asked if anyone knew anything about any of the companies. Most weren’t even aware these companies existed and none knew anything about them. They all told me to let them know how it worked if I went through with it, but they wouldn’t spend their money on it. While I still might one day just to see, I decided to donate to a foodbank instead.
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TAKEAWAYS
We are just beginning to scratch the surface of how the microbiome contributes to health and disease. While many of our experts have no doubt in its potential, the commercial and clinician applications of microbiome-science are well beyond the evidence, so here are some take home messages backed by science:
- We all have a unique microbiome, just like a fingerprint
- Take-home microbiome kits are cool, but don’t tell you much about the risk of disease
- Fecal microbiome transplants are effective for a Clostridioides difficile infection
- You are what you eat! Eating a plant-based, high-fibre diet is the best thing you can do for gut health
- Be conscious of antibiotic use – if your doctor says you don’t need them, you probably don’t
- Probiotics are not effective in the vast majority of cases, don’t waste your money
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