Diverticular Disease: a Gut Microbiota Perspective.

Gut microbiota composition and functionality are involved in the pathophysiology of several intestinal and extraintestinal diseases, and are increasingly considered a modulator of local and systemic inflammation. However, the involvement of gut microbiota in diverticulosis and in diverticular disease is still poorly investigated. In this review, we critically analyze the existing evidence on the fecal and mucosa-associated microbiota composition and functionality across different stages of diverticular disease. We also explore the influence of risk factors for diverticulosis on gut microbiota composition, and speculate on the possible relevance of these associations for the pathogenesis of diverticula. We overview the current treatments of diverticular disease targeting the intestinal microbiome, highlighting the current areas of uncertainty and the need for future studies. Although no conclusive remarks on the relationship between microbiota and diverticular disease can be made, preliminary data suggest that abdominal symptoms are associated with reduced representation of taxa with a possible anti-inflammatory effect, such as Clostridium cluster IV, and overgrowth of Enterobacteriaceae, Bifidobacteria and Akkermansia. The role of the microbiota in the early stages of the disease is still very uncertain. Future studies should help to disentangle the role of the microbiome in the pathogenesis of diverticular disease and its progression towards more severe forms.

Supplementation with Lactobacillus reuteri ATCC PTA 4659 in patients affected by acute uncomplicated diverticulitis: a randomized double-blind placebo controlled trial.

INTRODUCTION: Acute uncomplicated diverticulitis (AUD) is an inflammation of the colon diverticulum. We tested the efficacy of Lactobacillus reuteri 4659 (L. reuteri) in treating AUD. Primary outcome was reduced abdominal pain and inflammatory markers (C-RP). Secondary outcome was reduced hours of hospitalization. PATIENTS AND METHODS: A double-blind, placebo RCT was conducted with 88 (34M/54F mean age 61.9 ± 13.9) patients with a diagnosis of AUD. Group A (44 patients, 26F): ciprofloxacin 400 mg/bid and metronidazole 500 mg/tid for 1 week, plus L. reuteri/bid for 10 days. Group B (44 patients, 28F): same antibiotic therapy for 1 week, plus placebo/bid for 10 days. All patients completed a daily visual analog scale (VAS) for abdominal pain. RESULTS: Between days 1 and 3, the group A pain decreased by 4.5 points; group B decreased by 2.36 points (p < 0.0001). Between days 1 and 5, the group A decreased by 6.6 points; group B by 4.4 points (p < 0.0001). Between days 1 and 7, the group A decreased by 7.6 points; group B decreased by 5.6 points (p < 0.0001). Between days 1 and 10, the group A decreased by 8.1 points; group B decreased by 6.7 points (p < 0.0001). For C-RP value, the mean decrease between admission and after 72 h was 45.3 mg/L for group A and 27.49 mg/L for group B (p < 0.0001). CONCLUSIONS: Our RCT showed that supplementation of the standard AUD therapy with L. reuteri strain 4659 significantly reduced abdominal pain and inflammatory markers compared with the placebo group. It also resulted in a shorter period of hospitalization, and thus has economic benefits. TRIAL REGISTRATION: TRIALGOV: NCT03656328.

The Microbial Ecosystem Distinguishes Chronically Diseased Tissue from Adjacent Tissue in the Sigmoid Colon of Chronic, Recurrent Diverticulitis Patients.

Diverticular disease is commonly associated with the older population in the United States. As individual's age, diverticulae, or herniation of the mucosa through the colonic wall, develop. In 10-25% of individuals, the diverticulae become inflamed, resulting in diverticulitis. The gut ecosystem relies on the interaction of bacteria and fungi to maintain homeostasis. Although bacterial dysbiosis has been implicated in the pathogenesis of diverticulitis, associations between the microbial ecosystem and diverticulitis remain largely unstudied. This study investigated how the cooperative network of bacteria and fungi differ between a diseased area of the sigmoid colon chronically affected by diverticulitis and adjacent non-affected tissue. To identify mucosa-associated microbes, bacterial 16S rRNA and fungal ITS sequencing were performed on chronically diseased sigmoid colon tissue (DT) and adjacent tissue (AT) from the same colonic segment. We found that Pseudomonas and Basidiomycota OTUs were associated with AT while Microbacteriaceae and Ascomycota were enriched in DT. Bipartite co-occurrence networks were constructed for each tissue type. The DT and AT networks were distinct for each tissue type, with no microbial relationships maintained after intersection merge of the groups. Our findings indicate that the microbial ecosystem distinguishes chronically diseased tissue from adjacent tissue.

Probiotics in the Treatment of Diverticular Disease. A Systematic Review.

BACKGROUND AND AIMS: Diverticular disease is a common gastrointestinal condition. Low-grade inflammation and altered intestinal microbiota have been identified as factors contributing to abdominal symptoms. Probiotics may lead to symptoms improvement by modifying the gut microbiota and are promising treatments for diverticular disease. The aim of this study was to systematically review the efficacy of probiotics in diverticular disease in terms of remission of abdominal symptoms and prevention of acute diverticulitis. METHODS: According to PRISMA, we identified studies on diverticular disease patients treated with probiotics (Pubmed, Embase, Cochrane). The quality of these studies was evaluated by the Jadad scale. Main outcomes measures were remission of abdominal symptoms and prevention of acute diverticulitis. RESULTS: 11 studies (2 double-blind randomized placebo-controlled, 5 open randomized, 4 non-randomized open studies) were eligible. Overall, diverticular disease patients were 764 (55.1% females, age 58-75 years). Three studies included patients with symptomatic uncomplicated diverticular disease, 4 studies with symptomatic uncomplicated diverticular disease in remission, 4 studies with complicated or acute diverticulitis. Mainly (72.7%) single probiotic strains had been used, most frequently Lactobacilli. Follow-up ranged from 1 to 24 months. Interventions were variable: in 8 studies the probiotic was administered together with antibiotic or anti-inflammatory agents and compared with the efficacy of the drug alone; in 3 studies the probiotic was compared with a high-fibre diet or used together with phytoextracts. As an outcome measure, 4 studies evaluated the occurrence rate of acute diverticulitis, 6 studies the reduction of abdominal symptoms, and 6 studies the recurrence of abdominal symptoms. Meta-analysis on the efficacy of probiotics in diverticular disease could not be performed due to the poor quality of retrieved studies. CONCLUSION: This systematic review showed that high-quality data on the efficacy of probiotics in diverticular disease are scant: the available data do not permit conclusions. Further investigation is required to understand how probiotics can be employed in this condition.

Diagnóstico microbiológico de las infecciones intraabdominales / Microbiological diagnosis of intra-abdominal infections

Las infecciones intraabdominales constituyen un amplio y diverso grupo de procesos intra y retroperitoneales que incluyen infecciones no complicadas, en las que el proceso infeccioso se limita al órgano o tejido de origen (apendicitis, diverticulitis, colecistitis…), y complicadas, cuando la infección se extiende y afecta al peritoneo desencadenando cuadros generales, como las peritonitis difusas, o localizados, como los abscesos intraabdominales. La mayoría se produce por perforación o inflamación de la pared intestinal, a partir de la flora gastrointestinal, y por tanto son infecciones polimicrobianas y mixtas, con predominio de bacterias anaerobias. El diagnóstico microbiológico es esencial para conocer la etiología y sobre todo la sensibilidad, en especial de las infecciones nosocomiales o comunitarias en pacientes de riesgo por el incremento de resistencia bacteriana, multirresistencia e implicación fúngica. A pesar de los avances en el diagnóstico microbiológico, en el caso de las infecciones intraabdominales sigue siendo directo, basándose en las tinciones y cultivos, y el progreso más notable es la introducción de la espectrometría de masas (MALDI-TOF) en la identificación de los patógenos implicados.De forma general se indican las recomendaciones sobre la recogida, transporte y procesamiento microbiológico de las muestras clínicas. Se comenta la etiopatogenia, la clínica y el diagnóstico microbiológico de las peritonitis primarias, secundarias y terciarias y de la peritonitis (y otras infecciones) asociada a diálisis peritoneal, de los abscesos intraabdominales (intraperitoneales, viscerales y retroperitoneales), infecciones de las vías biliares, apendicitis y diverticulitis (AU)

Intra-abdominal infections represent a large and wide group of diseases which include intra- and retro-peritoneal infections. Some of them could be defined as uncomplicated, where the infectious process is limited to the organ or tissue of origin (appendicitis, diverticulitis, cholecystitis…). Complications occur when the infection spreads to the peritoneum, triggering localised peritonitis and abdominal abscesses. Most intra-abdominal infections are due to perforation or inflammation of the intestinal wall. The microorganisms that cause these infections come from the gastrointestinal flora, and therefore produce polymicrobial infections mixed with a predominance of anaerobic bacteria. Microbiological diagnosis is essential to determine the aetiology and the susceptibility of antimicrobial agents of the microorganism involved, especially in nosocomial infections or in community infections in predisposed patients due to increasing bacterial resistance to antimicrobial agents, multidrug resistance and fungal involvement. Despite the advances in microbiological diagnosis, in the case of intra-abdominal infections it still remains direct, being based on stains and cultures, the most notable progress is the introduction of mass spectrometry (MALDI-TOF) for the rapid identification of the pathogens involved. This review will provide recommendations on the collection, transport and microbiological processing of clinical specimens. Comments on the pathogenesis, clinical and microbiological diagnosis of peritonitis primary, secondary, tertiary and peritonitis (and other infections) associated with peritoneal dialysis, intra-abdominal abscesses (intraperitoneal, retroperitoneal and visceral), biliary tract infections, appendicitis and diverticulitis are also presented (AU)

Two cases of Ruminococcus gnavus bacteremia associated with diverticulitis.

We report two cases of bacteremia with the anaerobic bacterium Ruminococcus gnavus. In both cases, the bacteremia was associated with diverticular disease. Preliminary conventional identification suggested peptostreptococci, and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis did not produce scores high enough for species identification. Finally, the bacteria were identified by 16S rRNA gene sequencing.

Role of probiotics in management of diverticular disease.

Patients with diverticular disease may experience a variety of chronic symptoms, including abdominal discomfort, bloating, and altered bowel habit. They are also at risk of complications, including hemorrhage, diverticulitis, abscess, and fistula formation. The potential role of abnormal colonic microflora in the pathogenesis of diverticular inflammation has led to investigation of novel therapies such as probiotics. Probiotics are microorganisms that may be of net benefit to humans when consumed. The rationale and safety of their use in diverticular disease is discussed and current literature is reviewed.

Microbiology and outcome of iliopsoas abscess in 124 patients.

To describe the microbiology and outcome of iliopsoas abscess (IPA) in a large case series, we analyzed 124 cases of IPA collected from 1990 through 2004 in 11 hospitals in Spain. Twenty-seven (21.8%) patients had primary and 97 (78.2%) had secondary IPA. The main sources of infection were bone (50.5%), gastrointestinal tract (24.7%), and urinary tract (17.5%). A definitive microbial diagnosis was achieved in 93 (75%) cases. Abscess culture was the most frequent procedure leading to microbial diagnosis, followed by blood cultures. Staphylococcus aureus, Escherichia coli, and Bacteroides species were the most frequent microbial causes: S. aureus was the most common organism in patients with primary abscesses (42.9%) and with abscesses of skeletal origin (35.2%), whereas E. coli was the leading organism in those with abscesses of urinary (61.5%) and gastrointestinal (42.1%) tracts. Mycobacterium tuberculosis was found in 15 patients, 4 of them associated with human immunodeficiency virus (HIV) infection. Twenty (21.5%) cases had polymicrobial infections; these were more common among patients with abscesses of gastrointestinal origin. Information on clinical outcome was available for 120 patients; 19 (15.8%) had a relapse and 6 (5%) died due to complications related to the IPA. Patients who died were older and more likely to have bacteremia and E. coli isolated from cultures. In conclusion, secondary IPA is more prevalent than primary IPA. Among those with secondary IPA, most abscesses are secondary to a skeletal source. A bacterial etiology can be identified in most cases. The overall prognosis of patients with this condition is good.

Qualitative and quantitative analyses of the bifidobacterial microbiota in the colonic mucosa of patients with colorectal cancer, diverticulitis and inflammatory bowel disease.

AIM: To characterize the bifidobacterial microbiota of the colonic mucosa in patients with colon cancer, inflammatory bowel disease or diverticuitis. METHODS: A sample of the distal colonic mucosa was taken during surgery from a total of 34 patients, twenty-one with diagnosed colorectal cancer, nine with diverticulitis and four with inflammatory bowel disease, requiring surgery for their condition. Bacterial DNA was extracted from the resected mucosal samples and bifidobacterial mucosa-associated microbiota was qualitatively and quantitatively determined by means of qualitative and quantitative PCR. RESULTS: Bifidobacteria were found in 100% of the samples from patients with diverticulitis or IBD and a 76% of those suffering colon cancer. The species B. longum and B. bifidum were the most widely found, followed by B. animalis, B. catenulatum and B. adolescentis. B. breve, B. dentium and B. angulatum were not detected in any sample. A significantly higher occurrence of B. longum was observed in patients with diverticulitis than in those with colon cancer or IBD (100%, 62% and 75%, respectively, P < 0.05). Similar results were obtained for B. animalis (56%, 0% and 25%, P < 0.05), while B. adolescentis was only found in the mucosa from patients with colon cancer (5 out of 21, 24%). At the quantitative level, patients with colon cancer or IBD showed lower counts of total Bifidobacterium (4.94 and 5.91 vs 6.96 log cells/sample, respectively, P < 0.05) and of the species B. longum (4.05 and 4.79 vs 6.76, P < 0.05) than those with diverticulitis. CONCLUSION: Aberrancies in mucosa associated microbiota are present in different intestinal diseases. This may indicate a role of the microbiota in the pathogenesis of these diseases.

Assessment of small intestinal bacterial overgrowth in uncomplicated acute diverticulitis of the colon.

AIM: Small intestinal bacterial overgrowth (SIBO) may contribute to the appearance of several gastrointestinal nonspecific symptoms. Acute diverticulitis is affected by some similar symptoms and bacterial colonic overgrowth. We assessed the prevalence of SIBO in acute uncomplicated diverticulitis and evaluated its influence on the clinical course of the disease. METHODS: We studied 90 consecutive patients (39 males, 51 females, mean age 67.2 years, range 32-91 years). Sixty-one patients (67.78%) and 29 patients (32.22%) were affected by constipation-or diarrhea-prevalent diverticulitis respectively. All subjects were investigated by lactulose H2-breath test at the entry and at the end of treatment. We also studied a control group of 20 healthy subjects (13 males, 7 females, mean age 53 years, range 22-71 years). RESULTS: Oro-cecal transit time (OCTT) was delayed in 67/90 patients (74.44%) (range 115-210 min, mean 120 min). Fifty-three of ninety patients (58.88%) showed SIBO, while OCTT was normal in 23/90 patients (25, 56%). In the control group, the mean OCTT was 88.2 min (range 75-135 min). The difference between diverticulitic patients and healthy subjects was statistically significant (P<0.01). OCTT was longer in constipation-prevalent disease than in diarrhea-prevalent disease (180.7 min (range 150-210 min) vs 121 min (range 75-180 min) (P<0.001)), but no difference in bacterial overgrowth was found between the two forms of diverticulitis. After treatment with rifaximin plus mesalazine for 10 d, followed by mesalazine alone for 8 wk, 70 patients (81.49%) were completely asymptomatic, while 16 patients (18.60%) showed only slight symptoms. Two patients (2.22%) had recurrence of diverticulitis, and two other patients (2.22%) were withdrawn from the study due to side-effects. Seventy-nine of eighty-six patients (91.86%) showed normal OCTT (range 75-105 min, mean 83 min), while OCTT was longer, but it was shorter in the remaining seven (8.14%) patients (range 105-115 min, mean of 110 min). SIBO was eradicated in all patients, while it persisted in one patient with recurrence of diverticulitis. CONCLUSION: SIBO affects most of the patients with acute diverticulitis. SIBO may worsen the symptoms of patients and prolong the clinical course of the disease, as confirmed in the case of persistence of SIBO and diverticulitis recurrence. In this case, we can hypothesize that bacteria from small bowel may re-colonize in the colon and provoke recurrence of symptoms.

Acute recurrent diverticulitis is prevented by oral administration of a polybacterial lysate suspension.

AIM: The main cause of acute diverticulitis is the abnormal accumulation of fecal bacteria within the diverticular lumen, leading to a balancing between normal probiotic microflora and pathogenic species; Gram negative Entero-bacteriaceae, mainly Escherichia coli and Proteus spp, are the genders that usually cause the disease-related symptoms, due to their ability to adhere to intestinal mucosa. The intestine is well known as the largest human lymphoepithelial organ and daily produces more antibodies, mainly secretory IgAs, than do all other lymphoid tissues. IgAs have different immune and anti-inflammatory properties. The aim of this study was to verify the efficacy of an oral immunostimulant highly-purified, polymicrobial lysate in the prevention of recurrent attacks of diverticulitis and in the improvement of symptoms. METHODS: The study was carried out on 83 consecutive patients suffering from recurrent symptomatic acute diverticulitis and with at least 2 attacks in the previous year; patients were randomly assigned to receive (group A) an oral polybacterial lysate suspension or to a no-treatment clinical follow-up as controls (group B). RESULTS: A total of 76 patients (41 in group A and 35 in group B) terminated the study period. the sums of the scores for symptoms, reported on day schedules, were calculated and examined by means of ANOVA statistical analysis. Statistical differences between group A vs group B were recorded after 1 month (p<0.05) and 3 months (p<0.01) of treatment with the oral polybacterial lysate suspension. CONCLUSIONS: Our data suggest that the administration of an oral enterovaccine for the prophylaxis of recurrent diverticulitis is effective and well tolerated, probably due to a direct stimulation of IgA-mediated mucosal defences.

Disease-dependent adhesion of lactic acid bacteria to the human intestinal mucosa.

Their adhesion to the intestinal mucosa is considered one of the main reasons for the beneficial health effects of specific lactic acid bacteria (LAB). However, the influence of disease on the mucosal adhesion is largely unknown. Adhesion of selected LAB to resected colonic tissue and mucus was determined in patients with three major intestinal diseases (i.e., diverticulitis, rectal carcinoma, and inflammatory bowel disease) and compared to healthy control tissue. All strains were observed to adhere better to immobilized mucus than to whole intestinal tissue. Two strains (Lactobacillus rhamnosus strain GG and L. reuteri) were found to exhibit disease-specific adhesion to intestinal tissue. All tested strains, with the exception of L. rhamnosus strain GG, displayed disease-specific adhesion to intestinal mucus. These results suggest that strains with optimal binding characteristics for a particular intestinal disease can be selected.

Microbiologic profile of intra-abdominal infections at Belo Horizonte, Brazil.

Intra-abdominal infections (IAIs) represent one of the most common clinical problems in hospital practice, especially in surgical areas and centers of intensive care. The treatment of IAIs generally involves the draining of abscesses and empirical antimicrobial therapy. In this study, among 150 patients suffering from IAI, 106 (70.7%) yielded samples that presented microbial growth. Polyinfection was detected in 51.9% of the cases and varied from 2 to 9 distinct microbes per specimen. The overall mean number of micro-organisms isolated per patient was 2.17. Aerobic bacteria (as strict aerobes and facultative anaerobes), strict anaerobic bacteria, and fungi of the genus Candida represented 93.4%, 30.2%, and 13.2% of the cases positive for micro-organisms, respectively. The most common aerobic bacteria were those of the genera Staphylococcus, Escherichia, Proteus, and Streptococcus. Despite the frequent prior use (52%) with antimicrobials of recognized action against strict anaerobes, these micro-organisms constituted 30.9% of the total isolates, and the most frequently found were of the Bacteroides fragilis group and Prevotella species. The high prevalence of anaerobes in the specimens obtained from IAI demonstrates the need to give greater importance to these micro-organisms by making available material and human resources to carry out culture of the anaerobes as part of routine hospital procedures.

Esophageal diverticulum associated with Aerococcus viridans infection in a loggerhead sea turtle (Caretta caretta).

A juvenile loggerhead sea turtle (Caretta caretta) stranded in Gran Canaria, Spain was necropsied. The turtle was underweight, had sunken eyes, and small amounts of crude oil were in the oral cavity. The most significant lesion was a large esophageal diverticulum at the junction of the esophagus and stomach. The diverticulum was full of gas and green mucoid fluid and a diffuse thick yellow fibrinonecrotic membrane covered the mucosa. The lumen of the diverticulum also contained moderate numbers of cephalopods, crustaceans, and anthropogenic debris including crude oil balls, plastics, and fishing lines. Histologically there was a severe diffuse fibrinonecrotic esophagitis. Aerococcus viridans was isolated from the diverticulum. This is the first report of an esophageal diverticulum in a sea turtle. Although A. viridans is a known pathogen of lobsters and fishes, there are no reports of A. viridans infection in sea turtles.