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Showing posts with label HGM. Show all posts
Showing posts with label HGM. Show all posts

Monday, 29 April 2019

Curious Cook: A time for gut feelings – Part 2

Scientists now think that human gastrointestinal microbiota should be classified as a human organ after discovering hormones that it produces can affect the body, brain and the enteric nervous system.

Curious Cook: A time for gut feelings รข€“ Part 2

Overindulging in food can distress your human gastrointestinal microbiota. Photo: VisualHunt


People are not just people. They are an awful lot of microbes too.
This quote from The Economist (2012) reflects the realisation that human gastrointestinal microbiota (HGM) is not just a collection of icky bugs lounging around in our guts. In fact, scientists now think that HGM should be classified as a human organ – many endocrinologists (specialists in hormonal disorders) certainly view the HGM as an organ in its own right after discovering hormones produced by HGM can affect the body, brain and the enteric nervous system (ENS, our body’s second brain).
Influential HGM-produced hormones include serotonin, dopamine, noradrenaline, gamma-aminobutyric acid, acetylcholine, histamine, etc. The hormones are not produced by single strains of bacteria either – as an illustration, dopamine is output by bacteria such as Bacillus cereusB. mycoidesB. subtilisProteus vulgarisSerratia marcescensS. aureus, etc.
Not all kinds of bacteria can survive in the HGM, being restricted to four specialised groups called Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria. A recent revision indicates there are about 100 billion (instead of the oft-quoted 100 trillion) bacteria in adult human guts and there are probably over a thousand species and sub-species of bacteria.
Investigating HGM bacteria is difficult as many are so specialised that they survive only in intestines and cannot be cultured. They are crucial for various digestive processes – without HGM, many foods are simply indigestible. For example, humans have no enzymes for digesting most complex carbohydrates – these can only be processed by HGM. The outputs from HGM include vitamins, minerals, short chain fatty acids (SCFA) and other nutrients which are passed through the gut walls into the bloodstream – it also supplies between 10% and 15% of the energy for adults.
HGM also enhances the immune system; intestinal bacteria produce antimicrobial compounds which help attack and destroy pathogens (disease-causing microorganisms) present in the intestines and these compounds can be adopted by the body – an example is anti-inflammatory compounds produced by Faecalibacterium prausnitzii.
Cohabiting bacteria within HGM do not attack each other – they manage themselves via a fascinating mechanism called quorum sensing.

How quickly things change

The microbial balance of HGM can change quickly, within a day or less, and this is a direct result of what the body has ingested. Problem foods are not always obvious and can mutate over time – what is easily tolerated before may trigger severe issues later, and nobody is really certain why. Idiosyncratic human differences mean that problem foods are not always the same between people, even if they share the same diet.
In Taiwan, my intestinal cramps were so severe that I thought I had developed gluten intolerance. Later, it seemed the Taiwanese buns and noodles made from heavily-processed white flour were a more likely cause – and I never had problems with flour before.
HGM is loosely divided into three enterotypes (effectively a catalogue of the types of bacteria within the HGM), and enterotypes are influenced by diet. The three types are simply classed as Type 1 (where the genus Bacteroides dominate the HGM), Type 2 (where Prevotella is prevalent), and Type 3 (where Ruminococcus is plentiful). Other genera of bacteria always exist within each enterotype – the Types simply indicate the largest bacterial group by proportion.
guts
Problem foods are not always obvious and can mutate over time.
Enterotypes can alter over time, normally due to prolonged dietary changes. Type 1 is associated with digestion of proteins and saturated fats. Type 2 is linked with carbohydrates and simple sugars while Type 3 prefers complex carbohydrates and insoluble fibres – note that these types are only fuzzy classifications which can overlap substantially. A sudden change in diet can promote certain bacteria temporarily (though in general the original enterotype will revert eventually) – but while the enterotype is disrupted, the event may manifest itself as bodily discomfort and/or diarrhoea or constipation.
Other enterotype disruptive agents include tobacco, medications (especially antibiotics), alcohol, stress, pesticides, pollution, bacterial invasion, etc.
Persistent disruption of HGM balance via long-term exposure to problem diets and disruptive agents will simply end up with HGM deterioration.

The effect of a dysfunctional HGM

Dysbiosis (impairment of the HGM) manifests itself in ways which may not appear connected to dietary issues – this is the disconcerting peculiarity: certain health problems do not seem linked to the probable root cause. However it is still too early to confirm direct causal relationships between HGM and disease – but, as an example, some findings about Parkinson’s Disease (PD) are worth noting.
Compared to normal people, patients with PD have much higher concentrations of E. coli bacteria in their guts, along with more bacteria associated with the production of lipopolysaccharides, an endotoxin which aggravates tissue inflammation. PD is also associated with constipation and “leaky gut” syndrome, where intestinal walls are weakened, allowing the dangerous interchange of pathogens and toxins between the intestines and the blood stream – this may be due to degradation of the intestinal mucus lining caused by excessive numbers of bacteria such as Akkermansia muciniphila. An initial major event during the development of PD appears to be damage to the neurons in the ENS which then spreads to the central nervous system and motor neurons in the brain.
Pathologies of other disorders such as autism, kidney disease, liver disease, metabolic syndromes (such as diabetes, obesity, heart disease) and gastrointestinal issues (such as Irritable Bowel Syndrome, Crohn’s Disease, Clostridium difficile infection, etc) now also appear traceable to dysbiosis. Whether a malfunctioning HGM is always the prime cause of these conditions is debatable – but regardless of the root cause, it is indisputable that dysbiosis can be a contributing factor in the progression of many diseases.

Oops – now what?

So if a bout of overindulgence or encounter with a disruptive agent distresses your HGM, there are some things to consider. Firstly, chances are good that balance will be restored over time, though recovery is affected by age – older people take longer to restore their normal enterotypes. However, in some cases, the HGM may never recover if the disruptive event is overwhelming – more on this later.
Next is awareness of the symptoms of disruption, and avoiding things which may further aggravate matters. As a personal example, a sense of unease and constipation are signals which prompt abstinence from alcohol and rich foods. It is now time for fructans and dietary oligosaccharides (insoluble fibres used as food by HGM), eg. inulin (found in leeks, okra, etc) and galacto-oligosaccharides (lentils, chickpeas, etc). By weight, the HGM in adults weigh around 500g – and normal daily excretion removes up to 20% of this mass. With this amount of attrition, HGM needs to feed well to propagate itself, especially after some trauma.
Third point is drink lots of water, particularly if suffering from alcoholic dehydration. Insoluble fibre also needs water to progress through the gut better.
Cheese
Aged cheeses and natural cheese rinds contain lots of good bacteria and can help counter HGM. Photo: The Star/Yap Chee Hong
Yoghurts and drinks fermented with probiotic bacteria are sold in many supermarkets. However, in almost all cases, over 99% of the bacteria (usually from the genera Bifidus and Lactobacillus) are killed by stomach acids before it reaches the intestines – so an alternative may be pills of bacterial spores which can survive stomach acids. Or ingest aged cheeses and natural cheese rinds which contain lots of good bacteria. Whichever option you choose, eat some insoluble fibre beforehand.

Recovering from dysbiosis

Frankly, some people may never recover fully from dysbiosis. Once gut pathogens are firmly established or the intestinal lining is severely compromised, there is no easy return to a harmonious gut environment – for example, treatments such as medications/antibiotics would likely damage the remaining good bacteria as much as the pathogens. Faecal transplants from healthy donors appear thus far the best option to treat dysbiosis-related gastrointestinal problems.

Prevention

As for other diseases now qualitatively linked to faulty HGM, the best preventive options are care and vigilance as reliable diagnostics are presently unavailable. Paying attention to your HGM may really save your life.
I enjoy overindulging occasionally with family and friends, and I do not intend to stop – however I am aware of the obligation to my HGM afterwards and this is something I then manage fastidiously via a temperate diet, or else risk damage and dysbiosis.

https://www.star2.com/food/2018/02/25/curious-cook-time-for-gut-feelings-part-2/


Curious Cook: A time for gut feelings, part 1

It is sheepish to admit, especially as I am normally a demure, diffident person – but nobody has ever accused me of being over-restrained at feasts, especially if fine food, lots of alcohol and good company are present. Needless to say, there are consequences, and in my case it often results in a hazy sense of bodily unease (which lasts for days), combined with a rock-solid bout of constipation.

Curious Cook: A time for gut feelings, part 1
The wooziness from drinking inevitably subsides after a while, but the guts can feel the consequences of bingeing long after. Photo: VisualHunt
Therefore I would not suggest anyone emulate this propensity for overindulgence – especially as I am not unaware of what is happening to the body in these situations. For example, there is increased risk of liver cirrhosis – and several million brain neurons were probably fried by the alcohol.
Perhaps up to 4% of all deaths worldwide are related to alcohol abuse, though surprisingly only around 20% of heavy drinkers actually develop cirrhosis. By heavy drinking, one definition is consuming 100ml (80g) or more of ethanol a day for a period of 10 years or longer.
Many countries use “units of alcohol” (UA) to measure alcohol consumption – a UA is 10ml (8g) of ethanol so a pint of beer would be 2 UA or more (it depends on the strength of the beer). Therefore 100ml (80g) of ethanol is simply 10 UA – and in case you are curious, the reason why 100ml of alcohol is only 80g by weight is because ethanol is lighter than water.
A bottle of wine has around 9-10 UA so to run a 20% chance of developing cirrhosis, statistically one has to drink at least a bottle of wine a day for several years. However, statistics do not really help if there is a genetic disposition for cirrhosis.
This might apply to a significant proportion of humans who are genetically unable to produce enzymes called Aldehyde Dehydrogenases (ALDH1 and ALDH2) which are needed to neutralise acetaldehyde, a toxic compound created during the processing of alcohol in the body.
Prime examples are most Asians who lack the ability to express ALDH1 and ALDH2, so excessive alcohol consumption may be considerably more toxic for them. If you are interested, please read “A cure for hangover and – hic! – other holiday tales“.
Also, statistics indicate that consuming more than 26g of ethanol a day (just over 3 UA) increases the chances of bowel cancer by 21% – as Britain’s general incidence of bowel cancer is 6%, this increases the risk to about 7.25% overall.
gut issues HGM
Statistically, one has to drink at least a bottle of wine a day for several years to run a 20 chance of developing cirrhosis.

The Real Concern

Sobering as the facts about alcohol are, I have another more personal concern. The wooziness from drinking inevitably subsides after a while, but the disquiet is over the onset of intestinal issues after binging on food and alcohol – specifically the general feeling of corporeal unease and constipation which lasts for days.
The background for this worry is a little long-winded, so please bear with me.
My father eventually succumbed to complications after suffering for over 15 years from Parkinson’s Disease (PD). His PD was as severe as it was unexpected – nobody else in the family had the disease and it was immensely tragic watching him descend from an intelligent, outgoing human into someone who needed a handkerchief near the mouth at all times.
The severity of his condition meant that none of the usual PD drugs worked and he eventually contracted a severe infection in a hospital after treatment for respiratory issues. This finally killed him, and not in a pleasant way.
As such, PD is a subject which I keep an eye on – not least because as my father’s son, I have a statistically higher chance of developing this terrifying disease. There is some evidence that the disease may be hereditary (due to indeterminate research into various PARK genes) – but there is more evidence that PD can be caused by environmental factors.
Some characteristics of PD, apart from symptoms such as uncontrollable tremors and lack of motor control, are over-aggregations of proteins called alpha-synuclein (a-syn) in the nervous systems and the abundance of inflammatory compounds called cytokines in the brain – in combination, these compounds seemingly damage the brain neurons controlling motor functions.
Other lesser known symptoms of most PD patients are intestinal problems, mainly constipation.
gut issues


The concern about intestinal well-being is based on sobering research which found links between PD and the human gastrointestinal microbiota (HGM), the colonies of bacteria present in all human intestines.
A 2016 paper from the University of Wisconsin-Madison discovered that patients with PD have a significantly different composition of gut bacteria from normal people – this supported a hypothesis published by the University of Frankfurt in 2003.
When gut material from PD patients were transplanted into the guts of germ-free mice without PD, the test mammals began to display symptoms of PD. Even more curious was an experiment at CalTech where mice specially engineered to overproduce a-syn in their brains did not develop PD symptoms until gut matter from PD patients was implanted into their guts – control faecal material from normal people had a much smaller impact on motor dysfunction on such mice.
Despite the dramatic inferences, I should add that none of this is conclusive proof as yet (there may be other indeterminate causes of PD) – but it is certainly plausible that some relationship exists between a defective HGM and PD.
Interestingly, the Wisconsin-Madison team also provided a possible explanation: the flawed HGM in PD patients may cause significant overproduction of certain short-chain fatty acids (SCFA) (such as acetate, butyrate, propionate, etc) which are known to activate immune responses in neurons.
This was based on experiments where (i) SCFAs were fed to mice; (ii) faecal material from PD patients were transplanted into mice; and (iii) gut matter from normal humans were transplanted into mice – only the first two groups of mice developed symptoms of PD.
The University of Luxembourg and University of Alabama have also detected similar connections between PD and HGM. The Luxembourg paper goes further and suggested a link between a problematic HGM and the sleeping condition called Idiopathic Rapid-Eye-Movement Sleep Behaviour Disorder (iRBD) – and people with iRBD have a higher risk of developing PD in later life.
They also identified a relationship between certain HGM bacteria and depression.
An earlier 2012 joint paper by Harvard Medical School and Oxford University proposed that dysbiosis (an impairment of the HGM) is the root cause of many illnesses, including Irritable Bowel Syndrome, metabolic diseases, allergies, cardiovascular issues and, once again, neurological diseases.
Experiments done on mice at CalTech in 2013 also suggested a link between autism and HGM bacteria called Bacteroides fragilis which are notably lacking in children with autism, though it was unclear whether the link was causal or consequential.

HGM And Bingeing

Amazingly, it is only within the last few years that science is starting to quantify how seriously important HGM is to overall health – previously it was mostly theories and anecdotal inferences.
You probably know that humans have a second brain called the Enteric Nervous System (ENS) which also significantly affects well-being – this was discovered less than 20 years ago, and the HGM is contained within the ENS. If you are interested, read this short story, “The nine-metre brain“.
Therefore, the concern is that a bad (or excessive) diet can cause some sort of damage to HGM – which in turn can cause problems affecting the health of the rest of the body, including the brain. It is a plausible explanation as to why I (and probably many other people) feel disquieted and constipated for days after serious bingeing on rich food and alcohol.
Note that the ENS is made up of neurons (like the brain) and any activity that can destroy ENS neurons can probably spread to the brain eventually.
As an aside, laxatives are often used to treat constipation, but overuse can cause side-effects and obscure underlying HGM issues. How various laxatives work depends on their chemicals (and it is complicated to explain everything) – but they can be extremely effective (eg. magnesium citrate) so I would not suggest taking laxatives with a sleeping pill.

There will be more on how bad diets and over-indulgence affect the HGM in the next part.

https://www.star2.com/food/2018/02/11/curious-cook-gut-feelings-part-1/