TESTING THE MICROBIOME
Techniques are available to identify organisms in the gut microbiome by their DNA. This has resulted in a flurry of ideas, research and published papers, popular media articles and also commercial exploitation. There are no standardized testing protocols, making difficult any comparisons or reproducibility of the research. Studying, analyzing and interpreting microbiome data has many pitfalls (30240894), heterogenicity is found in studies (35795855, 36499127) but diverticular disease with its infection problems is an obvious candidate for such research.
The gut microbiome is in the caecum – the first part of the large intestine – in the closed circuits of the digestive system. The only way for microorganisms to get into the caecum is by swallowing them and the only way out is in the faeces. Diet is therefore an integral part of what organisms are found there and their survival depends on them having the right conditions and nutrients. Water supply is an important but forgotten part of diet. Change in diet can change the organisms present in 24 hours (28388917, 21885731). The microbiome composition is dynamic and test results can only apply at the time of testing. Diet supplements with live organisms may only change the microbiome contents if they are take continuously. Recognised diets, for example the Mediterranean diet, have distinct microbiome flora (39009882).
Antibiotics and medications can affect which organisms survive to be found in tests (34225544) but such personal information is not always noted for test volunteers. When researching a disease, the challenge is to distinguishing cause from effect (22356853). Ageing, illness and restricted diets can result in a less diverse microbiome. This is not ‘dysbiosis’ but a natural effect. Advocating a microbiome to be large in number and variety of organisms reflects a varied diet being beneficial for health. Most irritant and toxic strains of organisms, such as from food poisoning, are efficiently evacuated from the colon by diarrhea and are unlikely to be found in volunteers.
SAMPLING THE MICROBIOME
Examination of stool samples or rectal swabs are used to find organisms surviving from the microbiome. Another common means of sampling are biopsies taken during colonoscopies, but the microbiome and faeces have been washed out of the colon for this procedure leaving only species of organisms which adhere to the inner colon walls. The most relevant samples are those taken during operations for the infectious complications of diverticular disease but are less available. All samples are subjected to the conditions between sampling and testing.
DIFFERENT TYPES OF DIVERTICULAR DISEASE
The presence of diverticula observed on the colon or from the inside, i.e. diverticulosis, is the diagnostic evidence of the disease. People with and without diverticula and no symptoms, have been tested to see if different organisms in the microbiome could be responsible for the colon changes. Tests of the microbiome organisms present provided no evidence that they could be responsible for the formation of diverticula. (36775316, 34492052). An array of species can be found in the reports from researchers. The bacteria were mainly anaerobes which grow in the absence of oxygen. No significant differences were found between diverticula located in the left or right side of the body or along the length of the colon after the microbiome (29563543). There was no convincing evidence of microbiome ‘dysbiosis’ (36775316) and diverticulosis was not associated with altered gut microbiome or predictive of future diverticulitis (36987880).
When symptoms are produced in the presence of diverticula it is known as diverticular disease. Symptomatic uncomplicated diverticular disease (SUDD) can give pain and dysfunction without evidence of infection or inflammation. It is often confused with IBS, but research is pointing to the effects of the damaged colon muscles (33594008). Tests on the microbiome organisms of patients with and without SUDD have again provided no evidence of their involvement in this manifestation of diverticular disease (36775316) and no difference found between health, asymptomatic diverticulosis and SUDD in patients (36660603).
Samples from people with uncomplicated diverticular disease have been compared with samples from people with inflammatory bowel disease (IBD) – ulcerative colitis and Crohn’s disease. There were differences in which anaerobic bacterial species predominated but differences in diets and medications should be considered (28683448). An idea that the microbiome alone could be used for the diagnosis of diverticular disease (24894339) was not supported by diversity of the microbiota.
When diverticular disease shows signs of infection present, it is called diverticulitis. This can be confusing because in the past any painful symptoms were often called diverticulitis. Diverticulitis can be a ‘smouldering’ infection or acute, needing antibiotics at home or care in hospital. The condition is not always specified in microbiome tests comparing cohorts with and without diverticulitis. These tests have not shown consistently particular organisms being responsible for the infection. One investigation (36987880) followed up people with diverticulosis and retested them if they developed diverticulitis. A relationship between microbiome organisms and diverticulitis could not be demonstrated (35796855). Unknown in such studies is how often diverticular disease patients are prescribed antibiotics before volunteering.
A more direct way of looking for microorganisms which may be responsible for infections in diverticular disease is the sampling of colon parts removed in the surgical treatment of ‘complicated’ diverticulitis. An infected or perforated diverticula or abscess are sample sources for tests. Antibiotics and colon preparation for surgery are likely confounders of this type of study. Different range of organisms have been found between infected and uninfected parts of the same colon (36856684). Also reported are different organisms in a perforated diverticula compared with a healthy adjacent one (36556494). These authors considered that faeces in a diverticula promoted the development of specific microbial communities. There was more diversity of organisms in diseased parts than healthy tissue in one research report on complicated diverticulitis (40401932).
WHAT WAS IN THE MICROBIOME?
The research into the microbiome of DD has not revealed any particular organism to be responsible for its pathology or symptoms (37243442). The large and variable range of organisms found, which are listed in the many research papers and reviews, have little information on their individual activity or statistical significance. However, one report showed that microbiome composition explained 1.9% variation in the diseased state of SUDD but age was responsible for 10% (39180058).
Most of the organisms found in the colon are anaerobic, which means they can grow and ferment diet residues without oxygen. Before the current DNA testing techniques such organisms were very difficult to study in the laboratory (30240894). Now they have been found in both healthy people and people with DD in its various manifestations. Variation in an individual’s microorganisms are related to the speed at which they are passed out of the body (36171079). DD was not specifically mentioned in this report which indicated that these anaerobic organisms can continue to grow during their transit out of the body (and trapped in a diverticula ?) A study (27129485) found that the amount of the gas methane in breath tests was an independent predictor of finding diverticula on colonoscopy, due to faecal entrapment in diverticula (18936652).
WHAT NEXT FOR DIVERTICULAR DISEASE?
The recent studies have indicated that microbiome organisms are not the primary cause of DD and its symptoms. The problem is the damaged colon with its dysfunctional muscles and diverticula traps where faeces organisms can proliferate (26989376). The suggestion (40401932) that probiotics and faecal transplants are the answer does not seem appropriate. Probiotics have been tried and tested for a long time without any convincing evidence for use (33919818, 27014757). Somebody else’s transplanted microbiome organisms could equally get trapped in your diverticula unless this treatment is used against a persistent toxic microorganism.
There is a lot of research into DD but still no recommended drug except paracetamol for pain. Treatment by diet manipulation, antibiotics or surgery for the various symptoms have been available for a long time. Ideas and theories during that time still persist, particularly that a high fibre diet is necessary for prevention and treatment of DD. However, constipation and a low fibre diet are not always associated with diverticulosis (23891924). Many lifestyle and dietary risk factors persisting from the ‘fibre’ era have been questioned (22062360). Hydration level and water supply are not considered in diet surveys but are important for colon function with dietary fibre.
In 1910 diverticula on the colon were of obscure origin and rarely seen (20764923 page 378). About 60% of 80 known cases then had had clinical symptoms. The changes in the sigmoid colon wall were described. The contraction of the longitudinal muscles and the concertina shape of the circular muscles only in the area where diverticula were present has been a consistent finding ever since. The author also considered that the forward passage of intestinal contents was nearly impossible. Much later research showed that this more rigid colon wall, due to collagen changes, did not allow compensation for internal pressure from faeces and gas, producing blow-out diverticula in the weakest places, nor could the longitudinal muscles easily relax to push out further contents in the colon. Are fibre-bulked faeces with seeds the best option for this situation with its biomechanical element (33937291, 34599376?). Colon wall thickening is also found with diverticula in the right side colon but constipation is not a prominent symptom with this.
Based on chemically induced animal models of colitis, (16885693), colon damage in DD was thought to occur only after diverticulitis (25703217). Increasing research is now investigating and demonstrating the permanent nerve/muscle damage but symptoms without infection are only slowly being accepted and its cause is still unsure (37013200, 26458921). Research concentrates on surgical or antibiotic treatment and lifestyle influences. Colon muscle and neurotransmission are areas were drugs might help (22572680), but firstly, what causes this colon damage is key to prevention.
Worldwide epidemiology strongly points to cigarette smoking as the cause of DD. Increase in incidence and mortality during the 20th century correlates with known smoking related diseases such as lung cancer. The damage to the colon muscles, nerves and collagen by long term nicotine use reflects its pharmacology, with differences in nicotine metabolism with sex and ethnicity affecting its presentation. There is no doubt that every clinical progression of DD is made worse by smoking in many reports. DD started early in the 20th century and reached epidemic proportions with smoking in Western countries. Now, many alternative sources of nicotine are available supposedly to reduce smoking but do not address nicotine addiction. We have yet to find their effects on another generation’s colons but DD is already being found in younger people.
© Mary Griffiths 2025
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 the aim of improving health both globally and personably. It is available at https://www.pubmed.ncbi.nlm.nih.gov