Posts Tagged ‘Probiotics’

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.

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…)