“Greeting from both myself and my Microbiome” – Dr Rangan Chatterjee

Shining the most public and positive light on functional medicine in the UK? With a prime-time BBC slot and close to 3 million viewers does the new series ‘Doctor in the house’ provide the greatest public airing of a nutritional and lifestyle based approach to health management yet seen in the UK?

The doctor in question Rangan Chatterjee both practices as a GP and studies at the Institute of Functional Medicine in the USA. He has previously commented that “The health of the gut and its immune system is a fundamental factor for me to assess with every patient.” And in our article two weeks ago we reviewed a talk he recently gave at one of our health practitioner events on the topic of ‘Gut Health’. We were unable to cover all aspects of the talk in this previous article and we complete this overview today.

The talk by Doctor Chatterjee provided a fascinating overview of some of the mechanisms by which our gut microflora can affect the health of the host (us!) through production of short-chain fatty acids (‘SCFAs’), and the stimulation of mucin and secretory IgA production.

In addition the use of live native bacteria supplements in supporting gut health. The research reviewed reinforces the importance of diet in relation to gut health, particularly specific vegetables and certain fruits, and how such foods can be used to encourage the development and maintenance of a healthy gut flora.

Short Chain Fatty Acids

Research from the Scandinavian Journal of Nutrition elaborates on what SCFAs are, their role in the gut, and implications for health: “Short chain fatty acids (‘SCFAs’; acetic, propionic and butyric acid) are formed during bacterial fermentation of carbohydrates in the colon. The interest in SCFA production is related to an increasing body of knowledge of the physiological effects of these acids… In the 1960s, SCFAs were believed to be poorly absorbed, causing diarrhoea through osmotic fluid retention in the stool. However, it is now known that about 90% of these SCFAs are rapidly absorbed by the colon, stimulating water and sodium absorption. Fermentation of indigestible carbohydrate to SCFAs thus reduces the osmotic load and there is also increasing evidence that the individual SCFA may have specific roles, including beneficial health implications.”

In his talk Doctor Chatterjee noted research that elaborates on the wonderful complexity of our gut, the production of SCFAs, and their role in modulating the immune response. “The intestine is the major source of commensal microbes containing 10¹⁴ microorganisms of more than 500 different species. The numbers of bacteria generally increase going down the gastrointestinal tract, ranging from 100–1,000 per ml in the highly acidic environment of the stomach to ~10⁵ per ml in the upper small intestine and up to 10¹² per ml in the colon. However, the terminal ileum may contain larger numbers of bacteria than in the colon. These bacteria use complex polysaccharides and other components of mucus and undigested fibre as energy sources, producing essential metabolites such as biotin, short-chain fatty acids (SCFAs) and vitamin K.” The research further noted that:

“Immunomodulatory short-chain fatty acids (SCFAs) — such as butyrate, acetate and propionate — are generated by anaerobic digestion of oligosaccharides derived from mucus and dietary fibre by commensal Firmicutes and Bacteroidetes species in the colon. SCFAs are found at higher concentrations in the colon and thus probably have a more predominant role in shaping immune responses at this site.

Although the regulation of inappropriate immune responses is important along the length of the intestine, in the small intestine this is directed mostly at food proteins that can disseminate widely throughout the body, requiring tolerance mechanisms at both the local and systemic level.

Conversely, the colon acts as the main reservoir for the commensal microbiota that are essential for life, and its immune system seems to be geared to keep these organisms at bay and prevent inflammatory responses against them.

Thus, the colon contains a particularly thick layer of mucus that is produced by goblet cells, together with large numbers of mucosal IgA-producing plasma cells, IL-10-producing macrophages and FOXP3+ T-Reg cells.” 

Doctor Chatterjee noted that T-reg cells “Are a type of cell that acts like a peacekeeper. When we lose control of immunological balance, T-reg cells are inadequate in number to compensate for effector cells that are propogating inappropriate inflammation.”

A summary of the activity of SCFAs in the large intestine was provided as follows:

• Immunomodulatory effects in the large intestine are from SCFAs (such as Butryate, Acetate and Propionate)
• SCFAs are generated in the colon by anaerobic digestion of fibres by commensal bacteria
• SCFAs are found in high concentration in the colon and have prominent immune modulating effect here
• With both Metabolic and Immunological Capabilities for maintaining tolerance

Fibre rich, prebiotic foods that increase the production of SCFAs include Jerusalem artichoke, chicory root, onions, leeks, asparagus, starchy root vegetables (e.g. sweet potatoes) and dark green leafy vegetables.

Eating fermented foods can also help repopulate the gut with ‘good’ (i.e. friendly) bacteria and increase the production of SCFAs – see our blog on Fermented Foods.

Mucins & The Mucin Layer

Doctor Chatterjee noted in the relationship between our gut and immune system: “Dynamic interactions between our microbes and our immune system have both local and systemic responses. Gut lining is not immunologically inert especially through mucins.”

Research on U.S. National Library of Medicine provides an explanatory overview on mucins and the mucin layer – “The functional integrity of the intestinal mucosal epithelial cells depends on the coordinated regulation of the mucus layer, the intercellular tight junction, epithelial cells, and host innate and adaptive immune response. The mucus layer overlying the epithelium secreted by the goblet cells promotes the elimination of gut contents and provides the first line of defence against physical and chemical injury caused by ingested food, microbes and the microbial products.”

Doctor Chatterjee provided a summary of pertinent points in relation to mucins, goblet cells, food choices and the importance of all to gut health:

• Mucins produced by goblet cells perform an important protective function.
• Mucins are easily disrupted by poor food choices and certain drugs.
• Dysbiosis and the loss of appropriate mucin production, leads to damage to Goblet Cells.
• Goblet cells are found buried inside epithelial tissue, they release proteins to prevent bacteria having direct contact with epithelial tissues.
• If we don’t have enough mucins we have direct contact – inflammation!
• Dysbiosis* changes the rate at which you can produce Mucins and therefore puts you at risk of inflammation. (*a state of microbial imbalance in the GI)

Mucins produced by goblet cells perform an important protective function (in the gut). Mucins are easily disrupted by food choices and certain drugs. Dysbiosis and the loss of appropriate mucin production leads to damage to goblet cells. Goblet cells are found buried inside epithelial tissue, they release mucins to prevent bacteria having direct contact with epithelial tissues. If we don’t have enough mucins we have direct contact and resulting inflammation.

Therefore it is clearly important to “Improve goblet cell production of mucins as this prevents direct adherence to the epithelial tissue and reduces inflammation.” So how can we achieve this on an ongoing basis? Doctor Chatterjee talked about a particular species of gut bacteria – Akkermansia muciniphila which has an important role in the mucin layer. In addition he highlighted diet, and particularly ‘Oligofructans’ which promote the beneficial growth of this gut bacteria.

The research reviewed by Dr Chatterjee provides an explanation of both these points:

Akkermansia Muciniphila

“Akkermansia muciniphila has been identified as a mucin degrading bacteria that resides in the mucin layer, and it is the dominant human bacterium that abundantly colonizes this nutrient rich environment. The close proximity of this bacterium to the human intestinal epithelium supports the hypothesis that it plays a crucial role in the mutualism between the gut microbiota and host that controls gut barrier function and other physiological and homeostatic functions during obesity and type 2 diabetes.”

Eating oligofructans increases the number of goblet cells and mucus layer thickness. Examples of food sources of oligofructans include onions, garlic, leeks, artichoke, yams, chicory root, artichoke, bananas, Brussels, cauliflower, broccoli. In a mouse model mucin production was increased 100 fold. In addition research presented by Doctor Chatterjee noted:

“A muciniphila produces a variety of products including SCFAs through mucin degradation. These substrates may serve as energy sources for other bacteria and for the host. Akkermansia muciniphila may contribute to the expansion of other beneficial species, while it may itself have a direct effect on host metabolism, consistent with rodent studies.”

A list of commonly available foods that promote Akkermansia muciniphila:

• Onions
• Garlic
• Leeks
• Artichoke
• Yams
• Chicory root
• Artichoke (the root type, not the spiky globe)
• Jicama or Yam
• Bananas
• Dandelion greens
• Brussel sprouts
• Okra
• Cauliflower
• Broccoli

 Faecalibactierium Prausnitzii

Continuing on the relationship between our bacteria and our GI tract, and how important diet is in the role of good gut health Doctor Chatterjee provided an overview of research into ‘Faecalibactierium prausnitzii’ an “anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn’s disease (CD) patients”

The research noted that: “A decrease in the abundance and biodiversity of intestinal bacteria within the dominant phylum Firmicutes*  has been observed repeatedly in CD patients. We found that a reduction of a major member of Firmicutes, Faecalibacterium prausuitzii, is associated with a higher risk of post operative recurrence of ileal CD”

* phylum Firmicutes – The various species of bacteria fall predominantly into 2 phyla – Firmicutes and Bacteroidetes which together account for more than 90% of the total population of the intestinal microbiota.

Therefore it is important to maintain a healthy balance of this bacterium. Indeed the research noted that “Faecalibactierium prausnitzii exhibits anti inflammatory effects on cellular and TNBS colitis models and tended to correct the associated dysbiosis”

A healthy and diverse diet is again the important aspect to promote a good balance of this bacterium. It can be increased by eating commonly available foods such as:

• Apples and cinnamon
• Chickpeas
• Broad beans
• Carrots
• Cabbage
• Parsnip
• Leeks
• Avocado
• Dark leafy greens and vegetables
• Grain-like seeds like buckwheat, quinoa, millet, and amaranth
• Sweet potato
• Okinawan sweet potatoes

Two Apples a Day

How old is the adage “An apple a day keeps the doctor away”? Doctor Chatterjee noted research regarding apple consumption and dysbiosis that lends further factual information on the topic of healthy eating:

“Apples also help to alter the pathobiont (these are commensals that alter their relationship with the host depending on environmental triggers) mix of bacteria in human guts when consumed regularly; suggesting a role for their use in mild to moderate dysbiosis induced inflammation and loss of tolerance. In a small but clinically interesting study, healthy adults noted an increase in Bifidobacteria species and Lactobacillus numbers also rose, but Clostridium. Perfringens, Pseudomonas and Enterobacteriaceae declined on a diet of 2 apples a day for 2 weeks.

 Apples help to alter the pathobiont mix of bacteria in the human gut. Healthy adults noted an increase in Bifidobacteria species and Lactobacillus numbers also increased but Clostridium, Perfringens, Pseudomonas, Enterobacteriaceae declined on a diet of 2 apples per day for 2 weeks.”

Live Native Bacteria Supplements & IgA

Secretory IgA  (Immunoglobulin A IgA, also referred to as sIgA) is an antibody found at high levels in all the mucosal surfaces of the body that plays a critical role in mucosal immunity. Secretory IgA serves as a ‘first line of defence’ in protecting the intestinal epithelium from, for example, enteric toxins and pathogenic microorganisms.

Doctor Chatterjee noted research that commented “IgA was originally recognized as an important factor to protect the host from mucosal pathogens. More recently, we have begun to appreciate that IgA plays an important role in steady-state conditions in the gut.” – i.e. in maintaining ‘eubiosis’, a state of healthy, balanced and stable gut microflora; the opposite of dysbiosis.

• IgA helps to fight mucosal pathogens
• Washes away problematic bugs
• Important role in the steady state of eubiosis in gut
• IgA can inhibit penetration of organisms and maintain eubiosis

Dr Chatterjee referred to research on the beneficial effects that “probiotic microorganisms”  can have on the gut. In particular, certain live  bacteria species such as Saccharomyces boulaardii, Lactobacillus sp and Bifidobacteria sp may:

• Boulardii improves enzyme functionality in the brush border and stimulates sIgA

Lactobacillus GG and Bifidobacteria have been shown in human models to increase:

• Interleukin 10
• Regulatory T cell production

Potential benefits of live native bacteria supplements in IBD:

Immunomodulatory

• Increases IL-10
• Induces T-reg cells
• Inhibits NF-Kappa B
• Inhibits Interferon Gamma by T cells

Local Effects

• Increases Mucin Production
• Inhibits Interleukin 8
• Maintains tight junctions and epithelial cell integrity
• Diminishes Intestinal Muscle Inflammation

Conclusion

Throughout the prime-time television series ‘Doctor in the House’ Dr Chatterjee is presented with a number of challenging, diverse and long standing patient conditions but in each case we see a patient-centred, ‘root cause’ centred model applied to the diagnostic and therapeutic programmes where the benefits are clearly visible.

Since most chronic disease of today are due to dynamic imbalance affecting multiple tissues, system and organs, let us hope that this series provides the impetus necessary for the NHS to review the present disease-centred model of medicine which is so outdated. Dr Chatterjee is a wonderful ambassador for Functional Medicine; which in my opinion is the medicine of today and the future.

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Dr Rangan Chatterjee qualified from Edinburgh University Medical School in 2001 and has been practising medicine ever since. He has completed Membership for the Royal College of Physicians as well as Membership for the Royal College of General Practitioners. Initially, he worked as a hospital doctor for 6 years and has spent the last 7 years working in General Practice. Rangan also holds a BSc Honours Degree in Immunology and is a member of the Institute of Functional Medicine in the United States where he has undergone extensive training. You can find out more about him on his website.

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If you have any questions regarding the health topics that have been raised, or any other health matters please do contact me (Amanda) by phone or email at any time.

amanda@cytoplan.co.uk, 01684 310099

Amanda Williams and the Cytoplan Editorial Team: Joseph Forsyth, Simon Holdcroft and Clare Daley

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References are available upon request.

Last updated on 2nd February 2016 by cytoffice