Digestive Health & The Gut Microbiome

“All disease begins in the gut” – Hippocrates

Although Hippocrates didn’t know about the gut microbiome when stated this about 2,400 years ago, modern medicine is only now beginning to understand how right he was. More and more research is coming to light how good gastrointestinal health (especially the gut microbiome – the community of microorganisms living in the gut) is vital to a person’s overall wellbeing, and that an unhealthy microbiome composition can contribute to a large number of illnesses, including:

  • Obesity (1)
  • Inflammatory Bowel Disease (2)
  • Psoriatic arthritis (3)
  • Type 1 and type 2 diabetes (4, 5)
  • Eczema (6)
  • Coeliac disease (7)
  • Arterial stiffness (8)
  • rheumatoid arthritis
  • autism spectrum disorder
  • depression
  • chronic fatigue syndrome.

The information on this page is so important when it comes to maintaining a healthy digestive tract. Digestive problems seem to be on the rise. When it comes to looking at the health of our gut, there are two aspects to consider. These are the gut microbiome and the barrier function of the gut.

The Intestinal Microbiome

Within our gut, predominantly in the large intestine, there live approximately 38 trillion (38,000,000,000,000) microorganisms. The amount of bacteria in our gut outnumbers the amount of human cells in the body (9), with over 400 known species of bacteria.  Our gut bacteria outnumber our cells, they have been around longer than humans and they will probably be around long after we have gone. Justin Sonnenburg, a microbiologist at Stanford University, said that we would do well to regard the human body as “an elaborate vessel optimised for the growth and spread of our microbial inhabitants”.

Amongst their other roles, the gut microbiome helps to promote normal gastrointestinal function, helps regulate metabolism, help fight off infections and is closely associated with our immune system (approximately 75% of our immune system is in the form of Gut Associated Lymphoid Tissue – GALT).

The role of the gut microbiome in health and disease, with inputs and outputs (10)

Digestive Health
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Negative influences on the gut microbiome

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Positive influences on the gut microbiome

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Negative effects of an unhealthy microbiome

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Positive effects of a healthy gut microbiome

Unfortunately, quite a few aspects of modern life can directly lead to an unhealthy gut microbiome composition:

  • Medications such as antibiotics (14), osmotic laxatives (15), proton pump inhibitors (antacids) (16) and Non-Steroidal Anti Inflammatories (NSAIDs) (17).
  • Chronic stress (physical or psychological) (18).
  • Chronic or long term infections.
  • Diets that are high in sugar, refined carbohydrates, and processed foods (19).
  • Diets that contain a low amount of fermentable fibre (19).
  • Lack of regular exercise (20).

An imbalance in the variety of bacteria can also cause health problems.

This imbalance is known as dysbiosis. Even gut dysbiosis with inadequate friendly bacteria can have a negative impact on a variety of health conditions. A lack of healthy gut bacteria has been associated with allergies and general autoimmune reactions.

For example, studies in Inflammatory Bowel Disease have revealed quantitative and qualitative changes of the gut microbiome (21) including some studies (22) that showed a bacterium with anti-inflammatory properties were less abundant in patients with IBD than in healthy individuals. In Crohn disease, concentrations of Bacteroides, Eubacteria and Peptostreptococcus are increased, whereas Bifidobacteria numbers are significantly reduced.

In dysbiotic situations, where the normal composition of the commensal bacteria is compromised, pathologies such as autoimmune diseases may result. (23) The dysbiotic populations, with no identifiable pathogens, can still cause susceptibility to immune-mediated diseases (24) and several mechanisms of the promotion of autoimmunity have been suggested (25). 

The gut microbiome and obesity

Today, obesity is recognised to be associated with changes in the gut microbiome diversity and composition. Studies have revealed the gut microbiome to be an environmental factor in the digestive process, by regulating fat storage (26) and by possessing the ability to increase the energy harvested from the diet. Moreover, its capacity to modulate signalling pathways could affect energy balance and metabolism (27).  Obesity and type-2 diabetes are also characterised by alterations in the gut barrier, which causes disruption in the relationship between the gut microbiome and the person. This permeability is caused by different disturbances: 

  • alterations in the gut microbiome composition and/or activity,
  • alterations in the expression, localisation and distribution of tight junction proteins (claudin, ZO-1 and occludin) leading to an increase in (paracellular) gut permeability;

 

microbiome obesity

What else we know about the influence of the gut microbiome

  • Gut microbiome composition influences response to chemotherapy and immunotherapy (28)
  • Gut microbiome composition defines glucose response to foods and can be used to personalise diet (29)
  • A high fibre diet influences gut microbiome composition and is related to better health (30)

The (not so hidden) cost of antibiotic use: what does it do to our gut microbiome?

Antibiotics undoubtedly have an effect on the gut microbes. Although they are perhaps the most important medical innovation of the 20th Century, they can cause a massive, quick loss of variety and a change in the composition of the gut microbiome. They do not fully discriminate between killing the bad bacteria they are supposed to and the good ones residing in us. While the development of antibiotics has hugely benefitted modern medicine and our health, their excessive and inappropriate use may be causing serious long-term consequences that are only now becoming evident. Though antibiotics are absolutely necessary in certain situations, it’s important to use them judiciously because of the phenomena of antibiotic resistance. According to the World Health Organisation, antibiotic resistance is one of the biggest threats to global health, food security, and development today (31). Antibiotic resistance occurs naturally, but misuse of antibiotics in humans and animals is accelerating the process.

Martin Blaser, Chair of the Department of Medicine, New York University Langone Medical Center, published an article in Nature that emphasises the potentially dangerous long-term consequences that arise from the indiscriminate overuse of antibiotics. (32) He argues that changes in our gut microbiome may even be fuelling the transmission of deadly organisms such as methicillin-resistant Staphylococcus aureus (MRSA) (33) and Clostridium difficile (34). This is not an enormous surprise, because one of the important roles of an intact microbial eco- system is to resist intrusions by pathogenic organisms.

It has been shown that even a single treatment of intravenous antibiotics, can cause a significant reduction in the variety of bacterial strains, and the development of the pathogen Clostridium difficile (35). C. difficile colonisation in the gut can lead to severe complications such as profuse diarrhoea and colitis (inflammation of the inner lining of the colon). Another study showed that a short course of the antibiotic Ciprofloxacin treatment influenced the abundance of about a third of the bacterial species in the gut, decreasing the taxonomic richness, diversity, and evenness of the community. (36) 

Antibiotics in food

Low dose antibiotics are routinely given to livestock in poultry and beef farming (37), to increase their growth and weight. A large proportion of antibiotic use in many countries is for agriculture. Several observational human studies, as well as rodent studies, have demonstrated that antibiotics tend to cause obesity in humans, even in tiny dosages found in food (37). Blaser also points out that individual and agricultural use of antibiotics cause permanent changes in the gut microbiome (14). Given what we know about the lack of diversity in friendly gut bacteria and how it contributes to a large number of diseases and complications, this is a huge concern. 

 

However, some questions about the gut microbiome remain unanswered. For example:

  • Are the gut microbiome alterations caused by the diet in obese people or associated with the genesis of obesity itself?
  • Are natural probiotics in food better than probiotic supplements?
  • Can microbes influence food choices and appetite?
  • Should all new drugs and food chemicals be tested on the gut microbiome?

In the years to come, future research will hopefully uncover the answer to these questions.

The Gut Barrier

The barrier function of the gut is one of it’s most important functions: to prevent foreign substances from entering the body. If you really think about it, the contents of your gut are never really “in” your body. The gastrointestinal tract is essentially a tube that passes from one opening, your mouth to another, which is your anus. Once you’ve taken what the body can absorb, any non-digested material will pass out in the form of waste products (faeces), without crossing the intestinal barrier and entering the bloodstream.

The intestinal barrier has a surface area of 32 square meters and as well as allowing absorption of nutrients, it prevents against the entry of antigens and microorganisms. The barrier has multiple layers. The first is an external physical barrier and the second is an inner, functional physiological barrier. Successful interaction of these two barriers allows appropriate permeability to nutrients be maintained, while keeping out the things that shouldn’t be absorbed. When the barrier system malfunctions and permeability becomes inappropriate, this is called leaky gut or intestinal permeability.

Leaky gut used to be the domain of alternative medicine practitioners, and was generally dismissed by mainstream medicine 20 or 30 years ago. Today however, there are over 2,000+ papers in PubMed on intestinal permeability, with an increase from 10 publications a year 30 years ago, to now over 100 per year.

There are numerous factors that affect the integrity of the gut barrier. These include:

  • Nutrition (38).
  • Infections and toxins, (which could be viral, parasitic infections, fungal overgrowth, heavy metals or mycotoxins / mould) (39)
  • Chronic stress (40).
  • Small Intestinal Bacterial Overgrowth – SIBO (41), and
  • Genetic factors. In one study, 70% of asymptomatic relatives of coeliac disease patients test positive for intestinal permeability (42).

Both intestinal (within the gut) and extra-intestinal (outside the gut) conditions are associated with intestinal permeability.

Intestinal conditions include:

Extra-intestinal conditions include:

  • Peptic ulcers
  • Autoimmune diseases
  • Infectious diarrhoea
  • Obesity
  • IBS
  • Metabolic disease
  • Inflammatory Bowel Disease
  • Parkinson’s
  • Coeliac disease, and
  • Alzheimer’s
  • Both oesophageal and colorectal cancer
  • ADHD

Similar items that disrupt the gut microbiome can cause leaky gut:, medications such as NSAIDs, antibiotics, antacid drugs and steroids, a poor diet, stress, infections, hormone dysregulation, and certain neurological conditions (such as head injuries with brain trauma, strokes and neurodegenerative conditions).

Bacterial endotoxins (toxin present inside a bacterial cell that is released when it disintegrates) or food antigens that pass through the gut barrier into the bloodstream can elicit an autoimmune response. They act as super-antigens to T-lymphocytes or provoke a response by molecular mimicry. Many bacteria have antigenic sites that are similar to human tissue. So the immune system can attack both. This is why you see a correlation between autoimmune disease and leaky gut (43, 44). The barrier function of the gut is one of it’s most important functions: to prevent foreign substances from entering the body. If the intestinal barrier becomes permeable (or leaky), large proteins can enter the bloodstream. Since the large proteins don’t belong in the bloodstream, the body’s immune response can be initiated and attack them. The loss of integrity of the gut barrier can can also release endotoxins derived from gut microbes into the bloodstream. 

Studies have demonstrated that this immune response may be critical in the development of autoimmune diseases, such as Hashimoto’s thyroiditis, Coeliacs disease and type 1 diabetes. Some experts in the field of mucosal biology like Alessio Fasano, have now stated that leaky gut is a prerequisite to the development autoimmunity, along with genetic and environmental causes. Several studies with good methodology have consistently demonstrated that a disrupted intestinal barrier is a key factor in the development of autoimmune disease (45). Research has identified a protein called Zonulin, which has been demonstrated to increase intestinal permeability in animals and humans. Researchers have also found that many autoimmune diseases, such as coeliac disease, inflammatory bowel disease, rheumatoid arthritis, type 1 diabetes and multiple sclerosis, and– are associated with abnormally elevated Zonulin levels and intestinal permeability. One study demonstrated that increased intestinal permeability preceded the onset of type 1 diabetes (46).

One of the main reasons some people choose to avoid wheat and other gluten-containing grains is that they contain a protein called gliadin, which has been demonstrated to increase the production of Zonulin and disrupt the integrity of the intestinal barrier.

There is one vital point to consider:

You don’t necessarily have to have gut symptoms to have a leaky gut. The first signs that you may have a leaky gut could be the development of an autoimmune disease such as rheumatoid arthritis, Hashimoto’s thryroiditis, or type 1 diabetes. You may not have any digestive symptoms at all.

The major take home message here is that leaky gut and an unhealthy gut microbiome are very common due to the way we live our lives in the modern world.

If you suffer from a leaky gut, you may have an unhealthy gut microbiome, and vice versa. Most important of all, if the gut microbiome and intestinal barrier are unhealthy, you may be suffering systemic inflammation, which can lead to the development of an autoimmune condition.

If you suffer from one of these conditions, one of the first steps that you may want to take is to rebuild a healthy gut flora and re-establish the barrier function of your intestine.

maintain-healthy-gut

How To Maintain and Restore A Healthy Gut

I can provide you with advice to optimise your gut health, by helping you avoid the factors that lead to an unhealthy gut microbiome and damage the intestinal barrier.

Using advanced diagnostic tests, I can assess your gut microbiota and your general gut health. I can also advise you of good probiotic and prebiotic (food to help the good bacteria flourish) supplements and advise you how to best restore your gut health. Not all probiotics or prebiotics are equal!

Some of the best probiotics and prebiotics require a practitioner’s order. 

Gut inflammation has many causes, but the most common are:

  • A standard Western diet, which is usually high in refined carbohydrates and sugars.
  • Ingestion of environmental toxins. 
  • Gut infections. Parasites, fungi or disease causing / opportunistic bacterial species.
  • Autoimmune diseases, such as Inflammatory Bowel Disease (Crohn’s disease or Ulcerative Colitis).
  • Intestinal dysbiosis, which is imbalance between the good and bad bacteria of the gut. Other conditions such as SIBO (small intestine bacterial overgrowth), can also cause inflammation of the gut.

Only the first two causes on the list are solely associated with diet:  a Western diet and environmental toxins. The others could possibly be modified with diet, but diet is not always the underlying root cause.

I can help you take the first steps in healing your gut by:

  • Providing you with nutrient dense diet plan for optimal digestive (and overall) health.
  • Helping manage your stress levels to improve your digestive health.
  • Providing advice on how to improve your gut microbiome.
  • Avoiding factors that can adversely influence your gut health
  • Improving the integrity of your gut barrier.
  • Choosing the best probiotics and prebiotics customised for you (prebiotics are so vital and often overlooked).
  • Giving general lifestyle advice to improve your gut health.
  • Telling you when you need to consult your doctor.

However, it may take some 3-6 months and perhaps even longer, to solve a chronic digestive complaint. This may be disappointing to hear, but it is important to have realistic expectations though if you want restore your gut health. You may have been suffering from the causes of gut inflammation most of your life and unfortunately, the inflammation will not resolve overnight.

Stress and gut health.

Apart from a poor diet, there are many factors that increase levels of stress in your life, such as:

  • Excessive training / overtraining
  • Poor sleep
  • Not engaging in pleasurable pastimes.

Stress can also wreak havoc on the health of the gut. There are many ways to mitigate the impacts of stress.

The Gut-Brain axis / connection is gaining more recognition in healthcare. The intestinal mucosa contains a network of nerves called the myenteric plexus, that are influenced by signals arising from the brain. In this sense, the gut is part of the nervous system, with signals from the brain easily affecting gut function. I’m sure that most people have experienced this. For example, the feeling in your gut when you get some bad, or the butterflies or churning effects that anxiety can cause. The two-way signalling that occurs between the gastrointestinal tract and the brain occurs in both directions. 

The biochemical changes that happen in the body at times of stress have significant and almost instant effect on gut function. Hormones called corticotropin releasing factors (CRF) play a central role in regulating stress responses, and CRFs have a powerful effects on the gut through modulation of inflammation and increasing gut permeability (47),

Importantly, having a healthy gut flora can moderate the gut permeability that arises from exposure to chronic stress.

Conclusion

Maintaining an intact gut barrier and proper balance of healthy gut flora is a essential, yet hugely under-appreciated, component of optimum health. So many different conditions can be affected by problems such as gut dysbiosis or intestinal permeability and the list continues to grow. It is clear that this should not be ignored or disregarded if you really want to optimise your health.

References

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3). Scher JU, Ubeda C, Artacho A, et al. Decreased bacterial diversity characterizes the altered gut microbiota in patients with psoriatic arthritis, resembling dysbiosis in inflammatory bowel disease. Arthritis Rheumatol 2015;67:128-39. doi:10.1002/art.38892

 

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