Archive for the ‘Related Topics’ Category

Gut Microbiome – The Basics

Tuesday, March 26th, 2024

A technique using DNA analysis now enables the identification of more types of bacteria that reside in and on the human body. Interest in the organisms found in the gut, known as the microbiome, has exploded in two directions in recent years. Do they have a part in disease and is there a commercial opportunity? The microbiome appears extensively in research papers and in all types of media and ‘health products’. Suddenly, the microbiome might be responsible for many diseases and needs to be controlled. Why do we have the microbiome, where is it, what is it for and what does it do? Is not easy to find among the barrage of ideas and theories.

The caecum is the first part of the large intestine (colon). Its wall is reinforced by immune tissue from the appendix to along the ascending colon to isolate the microorganisms contained within which are known as the gut microbiome. These organisms are acquired from dietary substances and some will survive in the residues of digestion. This is their only source since birth. The liquid ‘chyme’ from digestion enters the caecum from the small intestine (ileum) via a one-way valve (ileocaecal valve). Any reflux here produces small intestine bacterial overload (SIBO). Symptoms of this are not well defined but pain and bloating and IBS are mentioned.

The other import into the caecum microbiome is from the appendix. This is not an evolutionary relic but a safe refuge for the production of live microorganisms to supply and maintain the microbiome if it is depleted. When the output is blocked appendicitis ensues. Being without an appendix appears to increase the risk of infection in diverticular disease.

The liver also uses the food digestion pathway to get rid of detoxification chemicals and those which cannot be passed via the kidneys and urine such as heavy metals and pigments from red blood corpuscles. Bile products from the liver are recycled by the microbiome and returned to the liver for reuse.

When this digestion and body waste enters the caecum it joins the residues of several previous meals and itself will be diluted by several following meals. Colon wall muscles produce mixing movements before slowly advancing the content to the drying phase in the colon and the recycling of water. Because of the slowing of flow in the microbiome, ‘transit time’ from mouth to anus is not related to a complete meal. Similarly, it can take time for the colon to get rid of a toxic organism or irritant.

The array of organisms in the microbiome vary within and between people and are dynamic. They will only be there if they have the right nutrients and conditions to survive. There is an intimate relationship between diet and foodstuffs, and the type of organisms needed to deal with their digestion residues. This system is successful at the extremes of carnivorous or vegetarian diets.

What constitutes an ‘unbalance’ or ‘dysbiosis’ of good and bad bacteria in the microbiome is a human concept, as is the opinion that the microbiome always needs more in number and variety of microorganisms to be effective and healthy. Consider an individual with a restricted diet due to illness found to have a limited range of organisms in their microbiome. This is not dysbiosis but is the microbiome responding to diet. Taking prebiotics, probiotics or fermented food is just changing the diet and too much might not be helpful. Researchers looking for a link between the microbiome and diseases need to consider the effect of the disease on diet. Also, the gut-brain axis is a two-way communication system and neurotransmitter faults in diseases and drugs can also affect colon movement.

There are examples in nature where a lesser species is employed in a symbiotic relationship to solve a problem the host cannot deal with themselves. Powerful enzymes from the pancreas are produced to digest proteins in food but need to be destroyed before they attack the host’s tissues. They cannot be reabsorbed. When a stoma is formed by bringing the end of the small intestine to the outside of the body, the microbiome is not used and the surrounding skin can be attacked by enzymes. A stoma further along the colon, past the microbiome, does not have this problem. Cystic fibrosis patients have to take enzymes to digest their food. Sometimes the microbiome cannot cope with the quantity of enzymes and the ascending colon can be damaged. Only one pancreatic enzyme, elastase, is found in faeces. This is not harmful and is in fact used to show that the pancreas is working.

The microbiome is an integral part of body processes and has self-regulating properties which can be disrupted by pathogenic organisms and antibiotics. The colon itself is controlled by its nerve and blood supply which can change its movements. Not all health problems are caused by the microbiome which is part of an efficient recycling and disposal system which has served mankind for millennia.

© Mary Griffiths 2024

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Diverticular Disease: Men and Women

Wednesday, February 9th, 2022

 

Diverticular disease (DD) is an acquired disease that was first demonstrated early in the 20th century. Its appearance and increasing importance occurred in cigarette-smoking western countries, particularly the USA and UK, where the habit and nicotine addiction was widespread in the population. These countries are the main source of reports and statistics. DD can no longer be considered the inevitable diet related disease of the elderly. DD can be a long term (26872402), progressive (13444546) and chronic disorder (22777341) as well as the acute infection of diverticulitis and its complications. Differences between males and females have always been apparent in hospital and mortality statistics where females predominate.

Diverticula – the small grape-like hernia – need to be seen on the colon before the disease can be diagnosed. Once they are present they are there for life. The data used to describe DD is in effect a measure of investigations, where and when they took place in the disease progression. For example, the same person could figure in post-mortem, mortality and hospital admission data but the diverticula could have been there for 40 -50 years. Similarly, ‘risk factors’ are for symptoms resulting in investigations revealing DD but are not the cause of DD. The current interpretation of data show DD in more men than women up to the age of 50 – 60 years, then proportions are reversed with more women in surveys measuring investigation of DD. No explanation has been offered for this effect (33727769) except hormone differences which of course cannot be disputed.

Eastwood (873339) considered factors which might influence a decision to investigate symptoms for a diagnosis of DD. Does a complicated selection process operate for a family doctor’s referral to a hospital consultant for an investigation? The presentation of symptoms or the seeking of medical advice, or social or geographical factors may affect data. Other influences mentioned in reports are costs and hospital capacity.

Because of low risk of colon cancer, internal examination, now usually by colonoscopy, are not considered necessary below the age of 50 years unless there are potentially dangerous symptoms. However, both diverticulosis, where diverticula are found without symptoms, and their infection ie diverticulitis, are found before the age of 50 years (15882243, 20604970). CT scanning for suspected appendicitis revealed 14% of the under 20 yrs. And 40% of those between 20 and 39 yrs. had evidence of diverticulosis. (33727769). Anybody with diverticulosis could get diverticulitis infection and nobody knows why. Symptoms of pain and dysfunction in males is more conspicuous than in females where it is part of their biology Males get investigation and diagnosis and earlier surgical treatment for DD than females (9860333).

Women with abdominal pain and bowel dysfunction are diagnosed quickly with Irritable Bowel Syndrome (IBS) (9262978). IBS is based on symptoms, but women have many symptoms peculiar to them that are not included in the research criteria for IBS (9096434). There are many potential causes of abdominal pain unique to females (31943595) that without relief can prompt repeated consultations more than males – a characteristic of IBS. Females can be told they have IBS as young adults, until after the menopause and even in old age. IBS will include people with diverticulosis and diverticulitis (19861955) but if found this does not change the diagnosis of IBS, some researchers think that only infected diverticula can cause pain (16678561). Data on the number of people with DD up to the age of 50 to 60 yrs. will show more males than females because more males are investigated and diagnosed.

Around the age of 50 yrs. screening for colon cancer by colonoscopy occurs. Finding diverticulosis is common and does not show different rates for males and females although females are slightly older. In older patient groups without significant symptoms, there is again no difference between the sexes (22573184). Symptoms such as constipation related to colon ageing at 60 to 70 yrs. old also appear to be the same. Differences between males and females appear if and when symptoms of DD become problematic and potentially serious. Females outnumber males when investigations are needed for episodes of diverticulitis or chronic complications of DD. This can be the first diagnosis of DD and younger age and female gender are independent risk factors (30647541). Frequently the female patients were found to have previously been diagnosed with IBS. Females and a preoperative diagnosis of IBS were also independent risk factors for persistent symptoms after sigmoidectomy (32077416).

For decades since the 1960s DD was considered a diet related disease of the elderly. Eating a low level of dietary fibre for at least 40 years produced diverticula. Adding wheat bran to meals was recommended to prevent the constipation then later any type of dietary fibre. This was supposed to prevent diverticula and diverticulitis development – now disproved. DD research concentrated in detail on diet and on hospital treatment for severe diverticulitis and life – threatening complications needing surgery. If and when dietary fibre was not helpful there were no other effective treatments for persistent, recurring or non-relenting, low grade inflammation symptoms that are now recognized (33727769, 22777341). Such symptoms have been described as ‘smoldering DD’ or ‘SUDD – symptomatic uncomplicated DD’ or the misnomer ‘post-diverticulitis IBS’ More females than males were diagnosed with SUDD in a survey (30023071) and this was a long-term condition (17431721). This is a painful part of some unfortunate patients’ experience of DD affecting quality of life and which does not reach the level of hospital treatment.

There is little information about DD in primary care (22572678). Extensive research at hospital level does not address the problems before patients see the specialists (17681003, 10601059). The number of diverticula can increase with age as can the extent if colon affected. There is no data on this aspect of DD to see if there is a difference between males and females. There are suggestions that more women than men are troubled by long term symptoms. In New Zealand NHS primary care, women had notably more antibiotics prescribed for them than men, particularly those under the age of 60 years, for 5 yrs. before they needed hospital attention for acute or non-acute problems. More antibiotic prescribing for women also continued for the next 5 yrs. of the survey (31314796). Chronic aspects of DD in women also appear in data from hospitals. Females were on average 5 years older than males when seen and had more chronic diverticulitis and strictures, but less bleeding than males (12907908).

This pattern continues in mortality studies. 300 unselected pathology colons found a higher incidence of DD in women and also the onset occurred at an earlier age. Before the age of 50, 21.7% of women and 4.2% of men had DD and diverticula were scattered along the colon in women (5679019). Men were more likely than women to have had surgery and have a surgical complication of diverticulitis as a secondary cause of death and are more likely to die in hospital. Women are more likely than men to die from chronic complications such as sepsis, obstruction or pelvic fistula and are more likely to die at home, in care or in a hospice (33216498, 33216487). Research is not providing reasons for these differences (30046356).

The situation with DD may be like emergency presentation at hospital for colon cancer (30734381). In 2 to 12 months before emergency, twice as many women than men had received a diagnosis of IBS or DD. This increased the risk for women aged 40 – 59 yrs. 20% of women had alarm symptoms before the emergency. These authors cite reports of longer diagnosis intervals, a higher risk of 3 or more consultations before specialist referral of women, different interpretation of symptoms in women compared with men and possible misattribution of symptoms in women to benign causes. New onset of ‘IBS’ in middle aged women was also of concern. Sex differences in health and medicine are increasingly recognized and women are disadvantaged (22699937). This includes DD were women appear to suffer a longer and chronic symptomatic disease which is less acknowledged or treated if and unless it becomes serious.

© Mary Griffiths 2022

REFERENCES

The numbers in the text are PMID references. PubMed is a free resource supporting search and retrieval of biomedical and life science literature with aim of improving health – both globally and personally. It is available at     https://www.pubmed.ncbi.nlm.nih.gov

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The Microbiome in Diverticular Disease

Thursday, November 10th, 2016

New techniques which identify individual species have lead to an explosion of research into the role of bacteria in the colon. The terms ‘microbiota’ (the bacteria) and ‘microbiome’ (the collection of bacteria) are widely used. Some researchers consider the microbiome as equivalent to a body organ. It is certainly a significant, integral and specific part of the digestive system in man and animals. In protein-eating humans the microbiome is in the caecum, the first bag-like part of the large intestine which receives the residues of digestion and has enzymes which degrade amino acids from proteins. In herbivores the microbiome is in an earlier part of the digestive system to deal with large quantities of plant material to extract maximum nutrients for its host with enzymes to synthesise amino acids (1). The microbiome in humans can have both beneficial and unhelpful effects. Its position in the human body and the role of an associated appendix had not been considered apart from the letter on this website (2). The appendix is no longer considered a vestigial organ (3), contains extremely variable bacteria (4) and may be involved in microbiome changes (5).

Differences in the bacteria present in the microbiome have been found in conditions  such as obesity, autoimmune diseases, autism and bowel disease including diverticular disease (DD). The microbiome and its surrounding immune system are linked (6).

  • Is the microbiome content a cause or an effect of a disease?
  • Is the presence of a specific organism significant?
  • Could the microbiome be changed to treat a disease?

These are the questions research is trying to answer. Bacteria will only survive and flourish if the conditions and nutrients are right for the species. There is great variation both between and within people, with age and even with geographical location. So far only diet appears to make a difference (1, 7). Does the microbiome match dietary residues and the disease affect diet? (more…)

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Appendix and Gut Bacteria (Microbiome) PJ 1999

Thursday, May 12th, 2016

This letter, published in 1999, is not now available on the website of the Pharmaceutical Journal. Only those later than 2000 can be accessed online. The letter has relevance to current interest in the gut microbiome and is published here with permission of the Pharmaceutical Journal.

Ulcerative colitis

More pieces for the jigsaw please

From Dr  Mary Griffiths, MRPharmS, MIBiol

SIR,�The report on the treatment of ulcerative colitis with E coli (PJ, August 28, p303) was another piece in the intriguing jigsaw of what produces the condition and its relapses. The mechanisms of inflammation and treatment and prevention of the damage to the inner surface of the colon by anti-inflammatory, steroid and immunosuppressant preparations are well documented. Dietary changes have little effect on ulcerative colitis, except for omitting milk in some patients. Sometimes, stressful, emotional events are linked with the onset of the disease and episodic symptoms and there may be a hereditary link.
Just suppose that the appendix is not a useless relic of evolution but a culture vessel and inoculating system to deliver actively growing organisms into the caecum. These are added to the chyme, which spurts from the ileocaecal valve, and to the residues of digestion of previous meals which are moved on more slowly when they reach the colon. The segmentation and pendulum movements of the first part of the colon mix its contents and there is fermentation and a rapid increase in the number of micro-organisms.
Why the body encourages this symbiosis is perhaps answered by the question of how does the body get rid of digestive enzymes before they are concentrated in faeces and give rise to self-harm? These enzymes are not normally reabsorbed in any quantity. The capacity of the system can perhaps be exceeded, for example, when single high doses of pancreatic enzymes given for cystic fibrosis damage the ascending colon. The diarrhoea caused by antibiotics is attributed to the ascent of resistant organisms such as Candida albicans, but a lower number of organisms to deal with digestive residues could also be involved. Appendectomy can result in more frequent colon upsets and a higher risk of certain cancers. In active ulcerative colitis, the colon walls are smooth and tubular and reduced segmentation means less effective mixing of its contents. E coli organisms surviving digestion could supplement the reduced numbers for the deactivation of digestive residues. Short-chain fatty acids normally produced by caecum fermentation have a beneficial effect in ulcerative colitis and the protection of mucous lining from enzyme action has explained the effectiveness of bismuth enemas.
I remember reading somewhere that there is an excess of acetylcholinesterase in ulcerative colitis which could be either a cause or effect of the lack of colon mixing movements and might be genetically determined; certainly, sympathetic stimulation would compound such an effect. Lack of movement causes toxic megacolon, which can be relieved by neostigmine injection. Nicotine stimulates acetylcholine release from postsynaptic neurones in the “gut brain” in the colon wall and would increase segmentation and caecum mixing. This explains why ulcerative colitis is less common in smokers, can relapse if smoking is stopped and symptoms can be reduced by nicotine patches.
Does anyone know of any other pieces of this jigsaw? Have any other anticholinesterase or cholinergic drugs ever been tried in ulcerative colitis to increase colon mixing? Do more readily available probiotics, eg, Lactobacillus species have any benefits? Are there any differences in enzyme activity in the faeces of patients when the disease is active or in remission. Many articles are not specific about which type of colon movement is involved in diseases and treatments, and ulcerative colitis is not always considered separately from Crohn’s disease.
Any comments on this speculative jigsaw puzzle would be appreciated.

Mary Griffiths
Macclesfield, Cheshire

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The colon’s little helpers

Sunday, February 6th, 2011

THE APPENDIX

A report in 2007 by doctors at Duke University USA (1) proposed that the appendix functioned as a safe house for beneficial bacteria in the human gut. Rather than assessing the significance of this proposal for human biology, news agencies and internet sites seemed more concerned with the creation v evolution argument. The appendix had previously thought to be a relic of evolution even though its structure suggested otherwise.

The authors were unaware that I had come to the same conclusion in 1999 (2). Their literature search had not picked this up. Their proposal was based on observations of bacteria and immune system activity in the film of mucus lining the appendix and colon. My conclusion followed the realisation of why there was a symbiotic relationship with bacteria in the colon (more…)

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