The presence of bacteria varies between colorectal adenocarcinomas, precursor lesions and non-malignant tissue.

BACKGROUND: A causal association has been suggested between certain bacteria and colorectal cancer (CRC). Only a few studies have, however, investigated the presence of these bacteria directly in colon tissue with conflicting results. It is thus uncertain which role they may have in prognosis and carcinogenesis of CRC. METHODS: Formalin-fixed and paraffin-embedded (FFPE) colorectal tissue samples from patients diagnosed with colorectal cancer (CRC)(tumor and paired normal tissue, n = 99), adenomas (n = 96), or diverticular disease (n = 104) were tested for the presence and bacterial load of Streptococcus gallolyticus (S. gallolyticus), Fusobacterium nucleatum (F. nucleatum), and Bacteroides fragilis (B. fragilis) using quantitative PCR. A subsequent broader search was conducted on a subset of samples using 16S ribosomal RNA gene sequencing. Finally, to evaluate the prognostic value, the bacterial status was compared to patient outcome. RESULTS: S. gallolyticus was not detected by qPCR in any of the investigated tissue samples and F. nucleatum and B. fragilis were found to be equally distributed in tumors, paired normal tissue, and diverticula, but significantly less present in adenomas compared to both tumors and diverticula. Neither, F. nucleatum nor B. fragilis status affected the five-year prognosis of the patients. The 16S rRNA gene sequencing data revealed that tumors were associated with the Prevotella genus while conversely adenomas and diverticula were associated with Acinetobacter genus. CONCLUSION: These findings do not support a role of F. nucleatum or B. fragilis during colorectal beginning, while S. gallolyticus was not implicated in the colorectal tissue of a Danish population. A potential role of the bacterial genera Prevotella and Acinetobacter was indicated, and requires further investigations.

The outcomes of Clostridioides difficile infection in patients with diverticular disease: a nationwide analysis.

Background: Clostridioides difficile infection (CDI) is one of the most common healthcare-associated infections. It contributes to significant morbidity and mortality among hospitalized patients in the United States. Prior studies suggest worse outcomes of CDI in patients with diverticulitis and increased risk for recurrent CDI. We conducted this study to evaluate the outcomes of CDI in patients with diverticular disease from a nationwide data sample (2012-2015).Methods: The National Inpatient Sample (NIS) database between January 2012 and September 2015 was queried for CDI admissions using the International Classification of Diseases, Ninth Edition, Clinical Modification [ICD-9-CM] codes 008.45, 562.11, 562.10, 562.12, and 562.13 for diagnoses of CDI and diverticular disease.Results: The study included 1,327,595 patients who were admitted between 2012 and 2105 for CDI. Out of all of the patients, 84,170 (6.34%) had a concurrent diagnosis of diverticular disease. After adjusting for confounding variables, the in-hospital mortality was lower [odd ratio (OR): 0.48, 95% CI: 0.44-0.52, p < .001] for patients with diverticular disease. The length of stay (LOS) was longer [10.5 versus 9.3 days, p < .001] and mean cost of hospitalization was significantly higher in patients without a history of diverticular disease.Discussion: In a nationwide population study, admissions with CDI, patients with a concurrent diagnosis of diverticular disease had lower in-hospital mortality. The observed results are different from prior studies and might be attributed to a higher burden of normal flora in those patients and increased use of antibiotic stewardship program across many hospitals nationwide.

Gut Microbiota in Health, Diverticular Disease, Irritable Bowel Syndrome, and Inflammatory Bowel Diseases: Time for Microbial Marker of Gastrointestinal Disorders.

Few data exist on differences in gut microbiota composition among principal gastrointestinal (GI) diseases. We evaluated the differences in gut microbiota composition among uncomplicated diverticular disease (DD), irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBD) patients. DD, IBS, and IBD patients along with healthy controls (CT) were enrolled in our Italian GI outpatient clinic. Stool samples were collected. Microbiota composition was evaluated through a metagenomic gene-targeted approach. GI pathology represented a continuous spectrum of diseases where IBD displayed one extreme, while CT displayed the other. Among Phyla, Biplot PC2/PC3 and dendogram plot showed major differences in samples from IBS and IBD. DD resembled species CT composition, but not for Bacteroides fragilis. In IBS, Dialister spp. and then Faecalibacterium prausnitzii were the most representative species. Ulcerative colitis showed a reduced concentration of Clostridium difficile and an increase of Bacteroides fragilis. In Crohn's disease, Parabacteroides distasonis was the most represented, while Faecalibacterium prausnitzii and Bacteroides fragilis were significantly reduced. Each disorder has its definite overall microbial signature, which produces a clear differentiation from the others. On the other hand, shared alterations constitute the "core dysbiosis" of GI diseases. The assessment of these microbial markers represents a parameter that may complete the diagnostic assessment.

Impact of treatments on fecal microbiota and fecal metabolome in symptomatic uncomplicated diverticular disease of the colon: a pilot study.

Symptomatic uncomplicated diverticular disease (SUDD) affects 50% of people having diverticulosis. We performed a pilot study assessing the effect of current treatments on fecal microbiota and metabolome in SUDD. Thirteen consecutive females with SUDD were treated with a 2-week therapeutic trial of 30 g/day fiber supplementation (3 patients), 1.6 g/day of mesalazine (3 patients), 900 billion/day of probiotic mixture VivoMixx® (3 patients), or 800 mg/day of rifaximin (4 patients). Stool samples were collected at entry (T0), at the end of the 2-week therapeutic course (T1), and 30 (T2) and 60 days (T3) after the end of the therapeutic course. Real-time PCR quantified targeted microorganisms. Fecal metabolome patterns were studied by high-resolution proton NMR spectroscopy. At cumulative analysis, symptoms significantly decreased at each time point during follow-up (p less than 0.0001), and only left-lower quadrant pain increased again at T3. The overall bacterial quantity was not altered by the treatments. The amount of Akkermansia muciniphila species was significantly reduced at T1 (p=0.017) and at T2 (p=0.026), while at T3 the reduction was not significant in comparison to enrollment (p=0.090). Fecal molecular profile showed significant changes at T1 and T2, while at T3 it became similar to that of T0. Differences were found for 18 of the quantified molecules (tryptophan, phenylalanine, tyrosine, 4-hydroxyphenylacetate, urocanate, X-6.363, X-5.779, uridylate, galactose, X-4.197, threonine, sarcosine, methionine, 2-oxoisocaproate, 5-aminolevulinate, alanine, leucine, valerate). Metabolome and microbiota changed in patients with SUDD under treatment, confirming a possible role of dysbiosis/dysmetabolome in the pathology.

Probiotics and Diverticular Disease: Evidence-based?

Diverticular disease (DD) is a common gastrointestinal condition. Clinical spectrum ranges from asymptomatic diverticulosis to symptomatic uncomplicated or complicated DD. Symptoms related to uncomplicated DD are not specific and may be indistinguishable from those of irritable bowel syndrome. Low-grade inflammation, altered intestinal microbiota, visceral hypersensitivity, and abnormal colonic motility have been identified as factors potentially contributing to symptoms. Probiotics may modify the gut microbial balance leading to health benefits. Probiotics, due to their anti-inflammatory effects and ability to maintain an adequate bacterial colonization in the colon, are promising treatment options for DD. This review focuses on the available evidence on the efficacy of prebiotics in uncomplicated DD.

Increased Faecalibacterium abundance is associated with clinical improvement in patients receiving rifaximin treatment.

Compositional and functional alterations of the gut microbiota are involved in the pathogenesis of several gastrointestinal diseases. Rifaximin is often used to induce disease remission due to its eubiotic effects on the gut microbiota. To investigate the correlation between changes in the gut microbiota composition and symptoms improvement in patients who present a clinical response to rifaximin treatment. Patients with ulcerative colitis (UC), Crohn's disease (CD), irritable bowel syndrome (IBS) and diverticular disease (DD) undergoing rifaximin treatment for clinical indication were enrolled in the study. Rifaximin was administered at the dose of 1,200 mg/day for 10 days. Faecal samples were collected at baseline and at the end of treatment; clinical improvement was assessed by Mayo score for UC, CD Activity Index (CDAI) for CD, IBS severity scoring system (IBS-SSS) for IBS and global symptomatic score (GSS) for DD. Twenty-five patients were included in the analysis and a clinical improvement was recorded for 10/25 (40%) of them. Microbial alpha diversity showed a slight increase in clinical responders (P=0.271), while it decreased in patients who did not improved (P=0.05). A significant post-treatment increase in Faecalibacterium abundance was observed in patients with a positive response (log2FC 1.959, P=0.042). Roseburia abundance decreased in both groups, whereas Ruminococcus decreased only in patients who clinically improved. Clinical improvement consequent to rifaximin treatment is associated with an increase in Faecalibacterium abundance. Achieving a positive shift in the gut microbiota composition seems a key event to obtain a clinical benefit from treatment.

Hot Topics in Medical Treatment of Diverticular Disease: Evidence Pro and Cons.

Symptomatic Uncomplicated Diverticular Disease (SUDD) is the most common clinical form of Diverticular Disease (DD). The therapy should be aimed at reducing both the intensity and frequency of symptoms as well as preventing complications. The pharmacological treatments include fibers, not absorbable antibiotics (for example rifaximin), anti-inflammatory drugs (for example 5-amino-salycilic acid) and probiotics, alone or in combination with other drugs. Although some of these treatments seem to be effective in treating SUDD, but their efficacy in preventing complications of the disease is still uncertain. It has been hypothesized that microbial imbalance associated with bacterial overgrowth of the colon, may be the key to the development of diverticular disease (DD). Therefore, drugs that can manipulate gut microbiota such as probiotics or rifaximine are considered as a potential key therapy. Rifaximine is able to modulate the intestinal ecosystem, restoring eubiosis. Traditionally, DD of the colon is thought to be related to low grade of inflammation. By analogy with other inflammatory bowel diseases mesalazine has been studied also in DD. There are several evidences that may support the use of mesalazine in the SUDD. Unfortunately, mesalazine cannot be used to prevent diverticulitis because of the paucity of high-quality studies. Currently, mesalazine has a limited place for the management of SUDD. In SUDD probiotics have been proven as an effective therapy in reducing abdominal symptoms, but unfortunately there has been limited number of relevant studies regarding efficacy of this therapy.

New concepts on intestinal microbiota and the role of the non-absorbable antibiotics with special reference to rifaximin in digestive diseases.

Digestive diseases are a broad range of chronic disorders that substantially and negatively impact the patients' quality of life. Here, we review our current understanding on the pathophysiology of hepatic encephalopathy, irritable bowel syndrome, and diverticular disease, with a special focus on the gut microbiota composition associated with these disorders. Furthermore, we review the current clinical practice for their therapeutic treatments, including probiotics, diet change, non-adsorbable disaccharides, and antibiotics. We highlight that broad-spectrum non-adsorbable antibiotics, such as rifaximin, are quite effective and safe for the treatment of all essayed digestive diseases.

Hinchey I and II diverticular abscesses: long-term outcome of conservative treatment.

BACKGROUND: The management of diverticular disease and its complications are an increasing burden to the health system. The natural history of conservatively managed diverticular abscesses (Hinchey I and II) is poorly described and it remains open to debate whether subsequent sigmoid resection is indicated after conservative management. This observational study compares outcomes of patients treated with conservative management (antibiotics +/- percutaneous drainage) and surgery. METHODS: All patients admitted at Christchurch Hospital with diverticulitis between 1 January 1998 and 31 December 2009 were recorded in a database. A retrospective analysis of patients with an abscess due to complicated diverticulitis was undertaken. Initial management, recurrence and subsequent surgery were recorded. The patients were followed until 1 January 2014. RESULTS: Of 1044 patients with diverticulitis, 107 with diverticular abscess were included in this analysis. The median age was 66 ± 16 and 60 were male. All patients had sigmoid diverticulitis and were diagnosed with a computed tomography. The median abscess size was 4.2 ± 2.1 cm. During median follow-up of 110 months, the overall recurrence rate was 20% (21/107). Recurrence varied according to initial treatment; namely antibiotics (30%), percutaneous drainage plus antibiotics (27%) and surgery (5%) (P = 0.004). The median time to recurrence was 4 ± 11.7 months, and most recurrences were treated conservatively; four patients underwent delayed surgery. CONCLUSION: Recurrence after diverticular abscess is higher after initial conservative treatment (antibiotics +/- percutaneous drainage) compared with surgery, however, patients with recurrent disease can be treated conservatively with similar good outcomes and few patients required further surgery.