The gut microbiome is one of the most interesting new ‘organs’ to be identified in humans because it offers opportunities for improving health at phases of life. One of the reasons is that it is much more closely linked to immunity than we thought. A number of scientists view the gut as more than just a digestive organ – its been called an immune organ too.
For some it offers an holistic approach to ameliorating some of the severe infections that we appear to be facing including Covid-19.
That holistic approach also extends to controlling obesity and weight management, to general mood and to inflammatory diseases.
What Is The Gut Microbiome?
The gut microbiome is actually a community of microbes including yeasts, fungi, bacteria and even viruses living in our gastro-intestinal tract. It is thought to be one of the largest, densest and most diverse microbial communities known to be within the human body. The other less diverse one but still important one is our skin microbiome.
Each of us can think of our gut microbiome as unique to us – rather like having a fingerprint. The groups of organisms, their number, species and sub-species are found nowhere else except in us as an individualised collection. This collection is dependent on our genetic make-up and what type of birth we experienced. It also changes over our lifetime but the these changes are typical rather than unique to us and it responds to our lifestyle. Factors like drug use, exercise, diet, smoking etc. all affect its make-up and ultimate performance.
When it comes to our consumption of food, our microbes in the gut form the first line of defense. These gut microbes have a symbiotic relationship with us. It protects us from the damage caused by pathogens and appears to be in constant communication with our immune system.
What really intrigues nutritionists are the complex interactions it has on human metabolism. It has been linked to various diseases including not only the obvious like gastrointestinal tract disorders but also our mental health, some autoimmune diseases, diabetes and obesity.
The make-up and composition of the gut microbiome is critical to good health. When we are in a healthy state, our microbiome is in a balanced, stable situation containing diverse forms of microbiota. When it is upset, we suffer dysbiosis where there is abnormal colonization of the gut. The beneficial microorganisms decline and disappear and are replaced by more harmful bacteria in particular.
The gut is interesting too in other ways. About 70% of all our immune cells are found in the gut. We also find that the number of gut bacteria is 1.3 times higher than the total number of total body cells.
The Intestinal Barrier
The gut is more than a hollow tube which filters out all the good nutrients. It is in fact a ‘tube’, of three distinct layers. The portion which allows food to pass through it and be digested is the lumen. We then have the intestinal epithelial cell layer covered in a protective layer of mucus. These epithelial cells sit on an inner layer called the lamina propria.
The whole 3-layer structure is able to act as a ‘gate keeper’. If it remains intact the gut serves as a mechanical and biochemical barrier but as with many membranes, it allows selective transport of nutrients into the bloodstream. What it also does is prevent pathogens from entering into the bloodstream and causing damage.
When the gut barrier is damaged or disrupted, food and microbial components which would normally be screened out or digested in the gut lumen cross and enter the blood stream. This disruption is often termed increased intestinal permeability but there is nothing benign about this phenomenon. The unfortunate result is to trigger a damaging immune reaction along with temporary inflammation. We can see why the intestinal barrier is so important for human health.
We know that 70% of our immune cells are located in the gut which seems extraordinary. We have tailored immune cells throughout different regions of the gut too. The small intestine such as the ileum has a different immune system to say the large intestine such as the colon for example.
Gut scientists want to know what each part of the gut is doing when it comes to triggering different immune responses. There is a complex interplay between our gut microbiota and the way the immune system functions.
Who Are The Bacterial Players?
We can estimate gut bacteria numbers. There are somewhere between 1013 and 1014 microbes in the gut. That equates to something like 10 times the number of cells in the body.
The weight of all these bacteria is somewhere between 3 and 5 pounds and the number of species is about 35,000 in total. Most of them have never been identified let alone characterised.
The main geni are Bacteriodes, Bifidobacterium, Escherichia, Lactobacillus, Prevotella, Eubacterium, Fusobacterium, Peptostreptococcus, Ruminococcus and Peptococcus.
The bacteriodes account for 30 per cent of all bacteria in the gut.
Given the great variety of bacteria let alone any other microorganisms, their genomic DNA is 150 times that of our own genome. It’s not surprising then that the human body has a huge interplay with alien DNA.
Controlling The Mucus Layer
The sticky layer coating the whole of the inner surface of the gut is probably one of the most special materials we have (Johansson et al., 2013). It is sugar-rich and protects the epithelial layers from abrasion by food, from invasion by pathogens but also helps coat fecal matter as it moves through the lower intestine. This is the crucial barrier between bacteria in food and faeces and the thousands if not millions of immune cells in the gut wall. Without it the gut just becomes imbalanced.
One of the key group of compounds in mucus are the mucins. These are secreted by goblet cells in the intestine. There seems to be a special role for them too in supporting symbiosis between resident gut microbes and us (Martens et al., 2008).
The mucins are mainly O-glycosylated proteins with potentially 80% carbohydrate by mass in human mucin 2 and porcine gastric mucins. Mucin O-glycans are long, branched structures composed of N-acetylgalactosamine, N-acetylglucosamine (GlcNAc), and galactose. They are terminated by fucose, sialic acid, or sulfated sugar residues.
These mucins are able to avoid digestion but on entering the large bowl are degraded by the microbiota providing a valuable energy source (Marcobal et al., 2013).
Antibiotic treatment may well disrupt the production of mucus based on animal studies but it is jump started by the presence of fecal matter and by the addition of bacteria. At the moment though it is unclear how mucins affect large intestine and bowel physiology.
What Do The Gut Bacteria Get Up To?
Digesting our food is what they get up to. They can only feed on what we eat.
One of the most important functions is carbohydrate fermentation and absorption. These bacteria all digest starch as an energy source as well as feed off prebiotic material such as soluble plant fibre. A diet rich in dietary fibre is seen as very effective in promoting good gut health through microbial fermentation (Topping & Clifton, 2001).
The gut bacteria breakdown large carbohydrates to produce SCFAs (short chain fatty acids) such as propionic acid, acetic acid and butyric acid.
The SCFAs play various roles in human physiology too. They activate the G protein-coupled receptors (GPCRs), act as energy sources, regulate cytokine expression in T cells, hence their importance in the immune and inflammation response, and the creation of regulatory T cells associated with histone deacetylase (HDAC) inhibition (Koh et al., 2016).
These SCFAs also reduce the risk of inflammatory bowel diseases (IBD).
A number of proteins like collagen and elastin are good sources of amino acids for bacteria.
These ‘good’ gut bacteria repress pathogens and stop their growth. One way is to out compete them for food and stop them attaching to the gut wall. They also produce bacteria killing molecules such as bacteriocins that specifically damage pathogens and they alter the pH by producing lactic acid.
The Role Of The Gut Microbiome In Obesity
We often discuss nutritional aspects associated with obesity. It is one of the rising health issues throughout the world. We looked at some of the research conducted on mice a few years back because it was interesting to observe a role for gut microbes.
Obesity is a medical condition of excessive fat accumulation. It has adverse effects on health and reduces life expectancy. It is also linked to a number of disease states like diabetes (type 2), sleep apnea, some cancers and osteoarthritis.
Researchers have found that our gut flora and fauna appear to regulate if not help manage how energy from food is stored as well as metabolised.
Take for instance mice which have a particular type of bacteria in their gut. They are protected effectively from becoming fat and obese by the presence of these particular gut microbes. When you transfer the gut microbes from mice which are obese to these lean mice, there is a significant rise in not only the content of their body fat but a greater risk from diabetes because of increased resistance to insulin.
This may seem far fetched and anecdotal but the research clearly shows differences in the gut microbiota of lean and obese mice, and that extends to humans too. These gut bacteria also alter rapidly when dietary conditions change.
Disturbances To The GI Tract – When It All Goes Wrong
Every so often, we experience turbulence in the gut which often takes the form of diarrhea. Two types are prevalent: bacteria diarrhea and antibiotic associated diarrhea (AAD).
Bacterial Diarrhea
This situation arises when enterotoxigenic strains of Escherichia coli or Vibrio cholera attach themselves to the small intestine wall and produce an enterotoxin. The enterotoxin produces watery diarrhea because it induces the mucosal epithelial cells to excrete water.
Some bacteria are more invasive. Salmonella spp. Shigella and Campylobacter are food borne bacteria which penetrate the intestinal mucosa. They produce a bloody, mucus-based stool and cause local inflammation of the gut.
Antibiotic Associated Diarrhea (AAD)
Very often antibiotics will kill much of our good gut microbiome. As a result, pathogens like Clostridium difficile and Botulinum bacteria get hold and cause severe inflammation of the colon. This is called pseudomembranous colitis.
Taking probiotics incorporating Lactobacillus sp. and Bifidobacterium help reduce the risk of pathogens gaining a foothold. It is a good idea to take such probiotic products during and after antibiotic consumption.
The other issue is that antibiotics also increase the degree of antibiotic-resistant bacteria.
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