Archive for the ‘Diverticular disease information’ Category

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?

Probiotics and prebiotics are tools to add particular species of bacteria to the microbiome (8).and are basically a dietary adjustment. Like the bacteria in food, probiotic bacteria may not reach or persist in the microbiome  unless they are taken continuously and survive stomach acid. A review of probiotics in the treatment of DD (9) found poor quality studies which gave insufficient data to reach a conclusion on effectiveness and could not be recommended for DD (10). Most bacteria in the colon are anaerobic i.e. do not need oxygen for growth. Popular ‘probiotic’ products are bacterial species which grow in dairy-based medium for factory production.

The relationship between DD and gut bacteria has been examined in the past and some organisms appeared to be associated (11, 12). New techniques have identified Proteobacteria as a species with sufficient prominence to suggest a way to diagnose diverticulitis (13). Previous studies found bacteria which produced raised levels of methane from the microbiome (11). Changes in the breath gasses when food residues reached the caecum confirmed methane production which could predict a finding of diverticulosis from colonoscopy (14).

Deleting a particular bacterial species from the microbiome would be a challenge. Antibiotics which kill a wide range of bacteria can have a devastating effect, sometimes leaving resistant organisms to flourish e.g. C. difficile. The production or recycling of substances useful to the body, also the deactivation of toxic by-products could be determined by the overall activity of the microbiome. Gut bacteria are used to release drugs to act directly in the colon, they can also inactivate drugs and influence their side-effects (15).

Early research has made use of faeces as the source of gut bacteria in experiments on germ-free mice. These have no microbiome. Faeces from humans with diseases have been given to mice and the effects observed The organisms  present in faeces will have already been selected by dietary residue composition. Mice are different from humans in digestive system anatomy, physiology, colon function and genetics and might not reflect real live humans (16). There has been some success in using human transplanted faeces to treat Ulcerative Colitis (UC) and persistent C. difficile colon infection. Why UC might be helped by added bacteria was discussed in the PJ 1999 letter on this web site (2).

Interest in the micrbiome has resurrected research into bacteriophages which are viruses to target and kill specific bacterial species. These have been used with success against other resistant bacteria in humans (17) and can work in the microbiome against C. difficile (18). Bacteriophages might be a way of dealing with specific disease-causing bacteria in the microbiome. Researchers are also considering antibiotics with a narrow spectrum of activity to target specific bacteria (19). The broad spectrum antibiotic “Rifaximin” which is not absorbed and passes unchanged into the colon is now used to reduce the activity of the microbiome in a disease which compromises liver activity and in traveller’s diarrhoea. Rifaximin in DD has received attention in Italy (20, 21, 22) The design of trials has made it difficult to separate the effects of Rifaximin from Mesalazine and dietary fibre levels. There is evidence and promise the Rifaximin can help reduce symptoms in uncomplicated DD but does not prevent relapse of diverticulitis. Rifaximin is not approved for treatment of DD in the UK.

The difference in the microbiome between people with DD and those without are producing speculation on how this might produce symptoms (23). Reviews are linking changes in the microbiome with gut inflammation and the development of conditions such as acute and chronic diverticulitis (24). However, linking microbiome changes to pre 1970s low fibre diets is an outdated approach to the cause of symptoms with DD (25).Recent research compared faeces from patients with and without symptoms against healthy controls who did not have diverticula. The number of bacteria did not differ between the three groups nor did the presence of many species of bacteria. Amounts of Akkermansia muciniphila species did differ between the groups and were associated with different levels of metabolic compounds in faeces between the groups, distinguishing the presence of diverticula and the presence of symptoms (26). Clinical trials are planned to examine the microbiomes of people with no symptoms from their diverticulosis for comparison with diverticulitis patients. What changes diverticulosis into diverticulitis has been a mystery for decades. The first episode of diverticulitis may have a different cause and risk factors than recurrent episodes (27). Hopefully microbiome research will illuminate these problems.

DD and other diseases must wait for research results but this has not stopped commercial exploitation and ‘health’ books and articles about the microbiome. Often there is no differentiation between mice and man. We are urged to get a good, rich and optimum microbiota but does this mean variety, high numbers and/or specific species of bacteria? How do we know what we have inside us? One popular advice is to increase the variety of bacteria in the gut by eating fermented foods from East Asia countries such as Korea or Japan. The old adage reappears that ‘Western’ diseases (eg DD) are less prevalent in those countries. ‘Eastern’ diseases, such as the world’s highest levels of stomach cancer are not mentioned.

© Mary Griffiths 2016

REFERENCES

1        Muegge BD et al. Diet drives convergence in gut microbiome functions across mammalian phylogeny and within humans. Science, 2011, 332, 970.

2        Griffiths M Pharmaceutical Journal letter 1999, and the article ‘The colons little helpers’on this website.

3        Bollinger RR et al. Biofilms in the large bowel suggest an apparent function of the human vermiform appendix. Journal of Theoretical Biology, 2007, 249, 826.

4        Guinane CM et al. Microbial composition of human appendices from patients following appendectomy. MBio, 2013, 4, pii: e00366-12 doi: 10.1128/mBio. 00366-12 (PubMed 23322636)

5        Sanders NL et al. Appendectomy and Clostridium difficile colitis: Relationships revealed by clinical observations and immunology. World J Gastroenterol. 2013, 19, 5607.

6        Wu HJ, Wu E. The role of gut microbiota in immune homeostasis and autoimmunity. Gut Microbes, 2012, 3, 4.

7        Wu GD et al. Linking long-term dietary patterns with gut microbial enterotypes. Science, 2011, 334, 105.

8        Marchesi JR et al. The gut microbiota and host health: a new clinical frontier. Gut, 2016, 65, 330.

9        Lahner E et al. Probiotics in the treatment of diverticular disease. A systematic review. J Gastrointestin Liver Dis, 2016, 25, 79.

10    Scarpignato C et al. Probiotics for the treatment of symptomatic uncomplicated diverticular disease: rationale and current evidence. J Clin Gastroenterol, 2016, 50 Suppl 1, S70.

11    Weaver GA et al. Incidence of methanogenic bacteria in a sigmoidoscopy population: an association of methanogenic bacteria and diverticulosis. Gut, 1986, 27, 698.

12    Gueimonde M et al. Qualitative and quantitative analysis of the bifidobacterial microbiota in the colonic mucosa of patients with colorectal cancer, diverticulitis and inflammatory bowel disease. World J Gastroenterol, 2007, 13, 3985.

13    Daniels L et al. Fecal microbiome analysis as a diagnostic test for diverticulitis. Eur J Clin Microbiol Infect Dis, 2014, 33, 1927.

14    Yazici C et al. Breath methane levels are increased among patients with diverticulosis. Dig Dis Sci, 2016, 61, 2648.

15    Deweerdt S. Drug metabolism: manipulating the microbiome. Pharm J, 2015, 294, 377.

16    Thi LAN et al. How informative is the mouse for human gut microbiota research. Dis Model Mech, 2015, 8, 1.

17    Ryan EM et al. Recent advances in bacteriophage therapy: how delivery routes, formulation, concentration and timing influence the success of phage therapy. J Pharm Pharmacol, 2011, 63, 1253.

18    Hargreaves KR, Clokie MRJ. Clostridium difficile phages: still difficult? Front Microbiol. 2014, 5, 184.

19    Yao J et al. A pathogen-selective antibiotic minimizes disturbance to the microbiome. Antimicrob Agents Chemother. 2016, 60, 4264.

20    Bianchi M et al. Meta-analysis: long-term therapy with rifaximin in the management of uncomplicated diverticular disease. Aliment Pharmacol Ther. 2011, 33, 902.

21    Moretti A et al. Role of rifaximin in the treatment of colonic diverticular disease. Clin Ter. 2012, 163, 33.

22    Koch M et al. Diverticular disease: towards 2020. An evidence-based approach. Recenti Prog Med. 2016, 107, 309.

23    Scaioli E et al. Pathophysiology and therapeutic strategies for symptomatic uncomplicated diverticular disease of the colon. Dig Dis Sci. 2016, 61, 673.

24    Spiller RC Changing views on diverticular disease: impact of aging, obesity, diet, and microbiota. Neurogastroenterol Motil. 2015, 27, 305.

25    Tursi A. Diverticulosis today: unfashionable and still under-researched. Therap Adv Gastroenterol. 2016, 9, 213.

26    Tursi A et al. Assessment of fecal microbiota and fecal metabolome in symptomatic uncomplicated diverticular disease of the colon. J Clin Gastroenterol. 2016, 50 Suppl 1, S9.

27    Peery AF. Colonic diverticula and diverticular disease: 10 facts clinicians should know. N C Med J. 2016, 77, 220.

Diverticular Disease: Genetics and Collagen

Thursday, July 9th, 2015

Compared with other diseases, advancements in science and technology left diverticular disease (DD) behind decades ago. Worldwide occurrence, poor quality of life, level of mortality and healthcare costs should have generated far more research effort. Preoccupation with dietary fibre levels, constipation and ageing has and still is stunting research. Fibre levels have benefits for constipation and symptoms but research into cause, prevention and other treatments has been overtaken by the necessary investigations into the surgical rescue of DD effects. Recently valid trials and surveys have disputed traditional thinking about a dietary cause and revealed a genetic factor. (more…)

Diverticular Disease And Colon Cancer

Thursday, April 3rd, 2014

Does having diverticular disease (DD) increase the risk of colon cancer (CC)?  One expert would say “yes” and another would answer “no”. Much depends on the design of studies, choice of patients, what data is fed into the computer for statistical analysis, interpretation of the results and what opinions and conclusions are made.

Research can be based on the occurrence of the two separate diseases, how many people with DD have CC and how many people with CC have DD (1). Comparison can be made with the levels of CC and DD which would be expected in the general population. Information can be expanded by including different types of cancerous lesions and their position in the colon. The diagnosis of DD is not so stable. Diverticulitis but not diverticulosis was indicated to be in a long-term causal relationship with increased risk of left-sided CC (2). However, these conditions at diagnosis can change. Diverticulitis can revert to diverticulosis with few further problems, or, diverticulosis can later progress to diverticulitis or even further to serious complications. This is a basic problem in DD research. (more…)

Diverticulitis: a wind of change

Sunday, December 2nd, 2012

There have been many changes over the years in the approach to diverticular disease (DD), even in the names used. Diverticular disease is the overall name. The presence of the grape-like diverticula on the outside of the colon results in a diagnosis of diverticulosis. Diverticulitis occurs when there is infection and inflammation of the diverticula but is often used when there are any symptoms caused by the disease.

Diverticulosis can have episodes of diverticulitis or complicated diverticulitis when problems such as bleeding, abscess, fistula or blockage need surgical treatment. This is a simplistic explanation of what might happen in DD in decreasing numbers, so that only a small fraction of people with DD ever need surgery. Any progression in the disease can stop and revert to symptomless diverticulosis at any time, some people with diverticulosis do not even know that they have it.

There has been confusion over many years about the symptoms with DD. (more…)

Colon Wall Muscles in Diverticular Disease

Sunday, September 2nd, 2012

MUSCLE LAYERS

Between the mucus producing lining and the outer layer of the colon wall, there are two major muscle systems. The inner circular muscles surround the colon, contraction can close the colon or they can act in waves to propel contents along. Between the appendix at the beginning and the rectum at the end of the colon, longitudinal muscles are gathered into three bands known as taenia. This arrangement allows contractions to shorten the colon and propel faeces without compressing them. Coordination between the two types of muscle can produce a variety of movements. An earthworm moving along soil is a good example to observe a similar system.

MOVEMENTS ALONG THE COLON

In the caecum, repeated circular muscle contractions mix the liquid contents (chyme). These change into backwards and forwards segmenting and propulsive movements to dry and move the mushy contents along the ascending and transverse lengths of the colon. Longitudinal muscles become more involved as faeces become more solid in the second, left side, of the colon. Occasional powerful contractions sweep faeces into the descending and sigmoid areas. Faeces are stored with the sigmoid area acting as a vertical warehouse with supporting arcs of circular muscle. Strong contractions of longitudinal muscles produce a concertina effect to push out colon contents on defaecation. The first half of the colon is controlled automatically by the vagus nerve from the brain. The left side has some local nerve reflexes and a person can have some influence such as when to defaecate.

CHANGES WITH DIVERTICULAR DISEASE

Changes in the colon musculature in diverticular disease (DD) were described even before the early 20th century when DD was rare, (1) and in many reports since. Muscle abnormality and dysfunction persisted in the colon after resection of the areas with diverticula (2). Long sections of the left colon can change in appearance without any diverticula which may only occur years later. The muscular abnormalities are the primary pathogenic mechanisms of DD (3). DD is only diagnosed when diverticula are observed, changes in muscles have had little attention especially in areas without diverticula. (more…)

Diverticular Disease: Updated Epidemiology

Thursday, May 3rd, 2012

“Ideas, like living organisms, have their natural history, growing from conception through a more or less tumultuous adolescence and reproductive maturity to an old age, when they act as a bar to further progress. During this time they become so modified that their origin is obscured” Sir Richard Doll (1)

Looking at the occurrence of a disease in time and place, and assessing what might have influenced changes, is known as the science of epidemiology. The theory, that diverticular disease (DD) was caused by low levels of fibre in the diet, has been prominent for about 40 years. This was based on the rarity of DD in Uganda compared with Western countries such as Great Britain or the USA. It was assumed that high levels of fibre in the Ugandan diet protected people from DD and that an increase in dietary fibre would prevent DD and its symptoms would be eliminated. This was a conclusion too far. It ignored the rarity of DD in people eating very little fibre (2,3) and that vegetarians can get DD (4,5). There is no evidence that a high fibre diet prevents DD. The theory is so entrenched that if DD appears in a country then it is assumed that its inhabitants have changed from their normal to a low fibre western diet. This is particularly incongruous when applied to right-sided DD in the caecum and ascending colon. Even the theory’s originators thought low fibre levels could not be relevant to this area (6)

Data from post-mortems, mortality statistics and surveys can provide information on the occurrence of DD, each aspect contributing to the overall picture. Song et al. (7) showed how colonoscopy findings, over time, could plot a rising prevalence of DD in Korea. Jun and Stollman in 2002 (8) collected results from research papers on the % of patients with DD in series of examinations by colonoscopy or barium enema Xray. They used these results to show that changes in the prevalence of DD varied greatly in time and between countries. Searching through later research reports mainly in the PubMed website gives this type of information for many more countries. (References to these sources are too numerous to include here). The results fall into 4 distinct patterns of when DD appeared and how numbers have changed over time until 2010. (more…)

How many people have diverticular disease and symptoms

Wednesday, January 12th, 2011

Nearly every review of diverticular disease (DD) and some research papers begin with statistics about how many people have DD at different ages. Figures regularly quoted for Western countries are 5% of the population by the age of 40, 25% by the age of 60 and 65% at 85 years. Variations are also described such as 50% of the population over 60 years, or 1/3 to 1/2 of the population will get the disease. In England and Wales this works out at over 5 million people which would rise with the aging population.

Trying to find the sources of these figures (more…)

All in a name – medical terms

Thursday, September 9th, 2010

 

Diverticular disease is an umbrella term which covers the physical changes in the colon wall and the effects from diagnosis to life-threatening complications and all the different symptoms which result from the disease. The muscular deformity with the characteristic bulging hernia or pouches called diverticula is known as diverticulosis. This definition is of a visible physical abnormality and does not indicate the extent of damage to the colon or describe its effects. Some people do not know that they have diverticulosis but after diagnosis about ¾ of patients have some type of symptoms. (more…)

What is Diverticular Disease

Thursday, August 5th, 2010

What is diverticular disease

 The large bowel becomes deformed in diverticular disease. The muscles appear to be permanently contracted so that the colon can be shortened and more corrugated. The bowel wall becomes ruptured particularly next to it’s blood vessels and pressure forces the inner layers to protrude through the wall to produce the characteristic grape-like pouches on the outside of the colon. There can be few of these pouches – called diverticula – or the whole colon can be affected. Similarly there can be a wide range of symptoms, but nobody knows how to stop the possible progression of the disease from symptomless, to a chronic, debilitating and recurring syndrome and on to life-threatening complications. Death rates in this country started at nil and have risen throughout the 20th century. With any other complaint, this statistic alone would prompt an outcry for research into causes, prevention and treatment. (more…)