Gut microbiota signatures in tissues of the colorectal polyp and normal colorectal mucosa, and faeces.

Background: Colorectal polyps are the most common precursors of colorectal cancer (CRC). The close relationship has been observed between colorectal polyps and gut microbiota. However, gut microbiota signatures among sampling sites in patients with colorectal polyps and healthy adults remain elusive. Aims: To learn about gut microbiota signatures in tissues of the colorectal polyp and normal colorectal mucosa, and faeces. Methods: We performed 16S rRNA gene sequencing and bioinformatic analysis for the microbiota in the normal colorectal mucosa, the colorectal polyps and faeces of adults with colorectal polyps (n = 24) and in faeces and normal mucosa of healthy adults (n = 16) in this preliminary trial. Results: The Ace and Chao indexes were higher in the normal colorectal mucosa and polyp tissues compared to faecal samples (P < 0.05). The composition of microbiota based on PCoA and ANOSIM analysis showed the significant differences only between faeces and tissues of the normal mucosa and polyp (P < 0.05). Based on the LEfSe analysis, the abundances of Bacteroides, Prevotella-2 and Agathobacter were higher, whereas the abundances of Haemophilus, Escherichia_Shigella, Fusobacterium and Streptococcus were lower in faeces both in patients with colorectal polyp and healthy individuals, compared with those in the normal mucosa in two groups or polyp tissues. In healthy individuals, the abundance of Fusobacterium was significantly higher in the normal colorectal mucosa than in faeces. Moreover, there was no significant difference in the abundance of Fusobacterium between the normal colorectal mucosa and polyps in patients with colorectal polyps, but it was significantly higher in the mucosa and polyps than in faeces. Remarkably, the abundance of Fusobacterium in the normal colorectal mucosa was significantly higher in healthy individuals than in the polyp group. Conclusions: The microbial structure in faeces differs from that in tissues of polyp and normal mucusa. Additionally, Fusobacterium may be a normal colonizer in colonic mucosa, and an abnormal increase of Fusobacterium detected in faeces may be related with the injury of the colorectal mucosa. The difference of the faecal microbiota and mucosal microbiota should be carefully considered in studies on gut microbiota in patients with colorectal lesions.

The differences between fecal microbiota and intestinal fluid microbiota in colon polyps: An observational study.

ABSTRACT: Generally, intestinal microbiota can be classified into intestinal cavity microbiota and mucosal microbiota, among which, the former is the default type. This study aimed to identify the differences between fecal microbiota and intestinal fluid microbiota in colon polys.This study enrolled patients with colon polys who met the Rome-III criteria to carry out 16s rDNA gene sequencing. Then, both fresh feces as well as intestinal fluid was sampled. Thereafter, α/ß diversities, together with the heterogeneities with regard to microbial function and structure were assessed among those intestinal fluid and fresh feces samples collected.According to bioinformatics analysis, difference in α-diversity was not statistically significant between intestinal fluid microbiota and fecal microbiota among patients with colorectal polyps (CPs). Non-metric multidimensional scaling analysis of ß-diversity revealed that differences were of statistical significance between both groups. In addition, linear discriminant analysis effect size analysis displayed great heterogeneities in intestinal microbiota of both groups, including Firmicutes, Clostridia, and Phascolarctobacterium. At the phylum level, difference (P = .016) in Spirochaetes was statistically significant between the intestinal fluid group and fecal group. At the family level, differences in Bacteroidaceae, Micrococcaceae, F16, Spirocheatacae, Enterobacteriaceae, Cardiobacteriaceae, Turkish Spirobacteriaceae, Bifidobacteriaceae, and Dethiosulfovibrionaceae were statistically significant between the 2 groups. At the genus level, there were statistical differences between the 2 groups in terms of Bacteroidetes, Rothia, Actinobacillus, F16, Treponema, Oscillospira, Turicibacter, Sharpea, Heamophilus, Veillonella, and Cardiobacterium.There are statistical differences in the composition between intestinal microbiota and fecal microbiota in CP patients, both of which are equally important and indispensable for analyzing the intestinal microbiota in CP patients.

Genomic and functional characterization of a mucosal symbiont involved in early-stage colorectal cancer.

Colorectal cancer is a major health concern worldwide. Growing evidence for the role of the gut microbiota in the initiation of CRC has sparked interest in approaches that target these microorganisms. However, little is known about the composition and role of the microbiota associated with precancerous polyps. Here, we found distinct microbial signatures between patients with and without polyps and between polyp subtypes using sequencing and culturing techniques. We found a correlation between Bacteroides fragilis recovered and the level of inflammatory cytokines in the mucosa adjacent to the polyp. Additional analysis revealed that B. fragilis from patients with polyps are bft-negative, activate NF-κB through Toll-like receptor 4, induce a pro-inflammatory response, and are enriched in genes associated with LPS biosynthesis. This study provides fundamental insight into the microbial microenvironment of the pre-neoplastic polyp by highlighting strain-specific genomic and proteomic differences, as well as more broad compositional differences in the microbiome.

Expression of Main Toll-Like Receptors in Patients with Different Types of Colorectal Polyps and Their Relationship with Gut Microbiota.

Abnormal activation of Toll-like receptor (TLRs) signaling can result in colon cancer development. The aim of this study was to investigate the expression of important TLRs in different histological types of colorectal polyps and evaluate their relationship with intestinal microbiota. The expression levels of TLR2, 3, 4, and 5 were analyzed in intestinal biopsy specimens of 21 hyperplastic polyp (HP), 16 sessile serrated adenoma (SSA), 29 tubular adenoma (TA), 21 villous/tubulovillous (VP/TVP) cases, and 31 normal controls. In addition, selected gut bacteria including Streptococcus bovis, Enterococcus faecalis, Enterotoxigenic Bacteroides fragilis (ETBF), Fusobacterium nucleatum, Porphyromonas spp., Lactobacillus spp., Roseburia spp., and Bifidobacterium spp. were quantified in fecal samples using absolute qRT PCR, and, finally, the association between TLRs and these gut microbiota- was evaluated by Spearman's correlation coefficient. Higher expression of TLR2 and TLR4 in VP/TVP and TA, and lower expression levels of TLR3 and TLR5 in all type of polyps were observed. The differences in TLR expression patterns was not only dependent on the histology, location, size, and dysplasia grade of polyps but also related to the intestinal microbiota patterns. TLR2 and TLR4 expression was directly associated with the F. nucleatum, E. faecalis, S. bovis, Porphyromonas, and inversely to Bifidobacterium, Lactobacillus, and Roseburia quantity. Furthermore, TLR3 and TLR5 expression was directly associated with Bifidobacterium, Roseburia, and Lactobacillus quantity. Our results suggest a possible critical role of TLRs during colorectal polyp progression. An abnormal regulation of TLRs in relation to gut microbial quantity may contribute to carcinogenesis.

Classification of Changes in the Fecal Microbiota Associated with Colonic Adenomatous Polyps Using a Long-Read Sequencing Platform.

The microbiota is the community of microorganisms that colonizes the oral cavity, respiratory tract, and gut of multicellular organisms. The microbiota exerts manifold physiological and pathological impacts on the organism it inhabits. A growing body of attention is being paid to host-microbiota interplay, which is highly relevant to the development of carcinogenesis. Adenomatous polyps are considered a common hallmark of colorectal cancer, the second leading cause of carcinogenesis-mediated death worldwide. In this study, we examined the relevance between targeted operational taxonomic units and colonic polyps using short- and long-read sequencing platforms. The gut microbiota was assessed in 132 clinical subjects, including 53 healthy participants, 36 patients with occult blood in the gut, and 43 cases with adenomatous polyps. An elevation in the relative abundance of Klebsiella pneumonia, Fusobacterium varium, and Fusobacterium mortiferum was identified in patients with adenomatous polyps compared with the other groups using long-read sequencing workflow. In contrast, the relatively high abundances of Blautia luti, Bacteroides plebeius, and Prevotella copri were characterized in the healthy groups. The diversities in gut microbiota communities were similar in all recruited samples. These results indicated that alterations in gut microbiota were characteristic of participants with adenomatous polyps, which might be relevant to the further development of CRC. These findings provide a potential contribution to the early prediction and interception of CRC occurrence.

An Overview of Gut Microbiota and Colon Diseases with a Focus on Adenomatous Colon Polyps.

It is known and accepted that the gut microbiota composition of an organism has an impact on its health. Many studies deal with this topic, the majority discussing gastrointestinal health. Adenomatous colon polyps have a high prevalence as colon cancer precursors, but in many cases, they are hard to diagnose in their early stages. Gut microbiota composition correlated with the presence of adenomatous colon polyps may be a noninvasive and efficient tool for diagnosis with a high impact on human wellbeing and favorable health care costs. This review is meant to analyze the gut microbiota correlated with the presence of adenomatous colon polyps as the first step for early diagnosis, prophylaxis, and treatment.

Periodontal Disease, Tooth Loss, and Risk of Serrated Polyps and Conventional Adenomas.

Growing data indicate an association between periodontal disease and the development of cancer. However, the evidence for colorectal cancer has been inconsistent and longitudinal study examining its precursor lesions is lacking. We prospectively collected information on periodontal disease and number of tooth loss in the Nurses' Health Study (1992-2002) and the Health Professionals Follow-up Study (1992-2010). Polyp diagnosis was acquired via self-reported questionnaires and confirmed through review of medical records. We used logistic regression to calculate the multivariate-adjusted ORs and 95% confidence intervals (CI) with adjustment for smoking and other known risk factors for periodontal disease and colorectal cancer. In this study, we included 17,904 women and 24,582 men. We documented 2,336 cases of serrated polyps and 4,102 cases of conventional adenomas among 84,714 person-endoscopies throughout follow-up. The ORs of serrated polyps and conventional adenomas comparing individuals with and without periodontal disease were 1.17 (95% CI, 1.06-1.29) and 1.11 (95% CI, 1.02-1.19), respectively. Compared with participants without tooth loss, those who lost ≥4 teeth had 20% (OR, 1.20; 95% CI, 1.03-1.39) greater risk of serrated polyps (P trend 0.01). Among never smokers, similar associations with periodontal disease were observed for both serrated polyps (OR, 1.20; 95% CI, 1.02-1.41) and conventional adenomas (OR, 1.12; 95% CI, 1.00-1.26). History of periodontal disease and possibly higher number of tooth loss may modestly increase the risk of developing colorectal precursor lesions. Our findings advance our understanding of the interplay between oral health, microbiome, and early colorectal carcinogenesis.

Prevalence of Helicobacter pylori among Sudanese patients diagnosed with colon polyps and colon cancer using immunohistochemistry technique.

OBJECTIVES: Infection with the bacteria Helicobacter pylori has been classified as class one carcinogen associated with increasing susceptibility of gastritis and gastric carcinoma. This study is aiming at investigating the prevalence of H. pylori among colon polyps and colon cancer patients. A descriptive cross-sectional hospital-based study was conducted between February and June 2017. Sixty-nine formalin-fixed paraffin blocks collected from colon polyps and colon cancer patients to detect H. pylori using immunohistochemistry technique. RESULTS: Of the 69 patients included in the study, 39 (56.5%) males and 30 (43.5%) were females, their age ranged from 21 to 80 years with a mean age of 47.1 ± 19.7. Of the 69 colon polyps and colon cancer patients, 44 (63.8%) were diagnosed as adenocarcinoma, 10 (14.5%) colitis, 15 (21.7%) juvenile polyposis syndrome. The results of immunohistochemistry technique showed the presence of 16 (23.2%) positive patients for H. pylori infection. Of these 16, 13 (81.3%) patients were diagnosed with adenocarcinoma and 3 (18.7%) patients were diagnosed with juvenile polyps. The results of H. pylori detection among the different colon polyps and colon cancer patients were showing a statistically significant association for H. pylori infection and adenocarcinoma, P value 0.028.

Clinical usefulness of FDG-PET/CT for identification of abnormal extra-cardiac foci in patients with infective endocarditis.

The aim of the study was to evaluate the ability to detect extra-cardiac foci by means of whole-body 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in patients with definite endocarditis (IE) according to the modified Duke criteria and investigate the clinical impact of the findings. From January 2011 to December 2015 we included 178 patients (mean age 66 ± 14 years, 25% female) with IE in this multicentre study. FDG-PET/CT was part of the work-up for extra-cardiac foci in the including hospitals and was performed at a median of 9 days (IQR 10) after IE was diagnosed. In 114 patients FDG-PET/CT identified 166 lesions: 52 (31%) infectious lesions, 21 (13%) cases of cancer, 7 (4%) cases of embolism, 60 (36%) reactive findings, and 26 (16%) other types of lesions. A total of 74 new extra-cardiac findings, not previously discovered by other modalities, were identified in 62 patients and resulted in additional investigations in 29 patients and a change in treatment in 18 patients (10%). The most frequent diagnoses discovered by FDG-PET/CT were colon polyps, cancer, and spondylodiscitis. There was a higher rate of findings leading to a change in treatment in patients above 67 years of age infected with other bacterial aetiologies than streptococci. FDG-PET/CT was useful to detect extra-cardiac foci. FDG-PET/CT findings may lead to unnecessary investigations. One out of 10 the patients with definite endocarditis had underwent a change in treatment regimen based on the FDG-PET/CT findings.

The BE GONE trial study protocol: a randomized crossover dietary intervention of dry beans targeting the gut microbiome of overweight and obese patients with a history of colorectal polyps or cancer.

BACKGROUND: Mouse and human studies support the promise of dry beans to improve metabolic health and to lower cancer risk. In overweight/obese patients with a history of colorectal polyps or cancer, the Beans to Enrich the Gut microbiome vs. Obesity's Negative Effects (BE GONE) trial will test whether and how an increase in the consumption of pre-cooked, canned dry beans within the context of usual diet and lifestyle can enhance the gut landscape to improve metabolic health and reduce cancer risk. METHODS/DESIGN: This randomized crossover trial is designed to characterize changes in (1) host markers spanning lipid metabolism, inflammation, and obesity-related cancer risk; (2) compositional and functional profiles of the fecal microbiome; and (3) host and microbial metabolites. With each subject serving as their own control, the trial will compare the participant's usual diet with (intervention) and without (control) dry beans. Canned, pre-cooked dry beans are provided to participants and the usual diet continually assessed and monitored. Following a 4-week run-in and equilibration period, each participant provides a total of 5 fasting blood and 6 stool samples over a total period of 16 weeks. The intervention consists of a 2-week ramp-up of dry bean intake to 1 cup/d, which is then continued for an additional 6 weeks. Intra- and inter-individual outcomes are assessed across each crossover period with consideration of the joint or modifying effects of the usual diet and baseline microbiome. DISCUSSION: The BE GONE trial is evaluating a scalable dietary prevention strategy targeting the gut microbiome of high-risk patients to mitigate the metabolic and inflammatory effects of adiposity that influence colorectal cancer risk, recurrence, and survival. The overarching scientific goal is to further elucidate interactions between diet, the gut microbiome, and host metabolism. Improved understanding of the diet-microbiota interplay and effective means to target these relationships will be key to the future of clinical and public health approaches to cancer and other major diet- and obesity-related diseases. TRIAL REGISTRATION: This protocol is registered with the U.S. National Institutes of Health trial registry, ClinicalTrials.gov, under the identifier NCT02843425. First posted July 25, 2016; last verified January 25, 2019.

INVESTIGATION OF ENTEROCOCCUS FAECALIS POPULATION IN PATIENTS WITH POLYP AND COLORECTAL CANCER IN COMPARISON OF HEALTHY INDIVIDUALS.

BACKGROUND: Colorectal cancer is one of the most commonly diagnosed cancers around the world. One of the factors involved in the development of colorectal cancer is the changes in the normal flora of the intestine. OBJECTIVE: In this study, the mean copy number of Enterococcus faecalis in people with polyps and people with colorectal cancer has been evaluated in comparison with healthy controls. METHODS: In this study, 25 patients with colorectal cancer and 28 patients with intestinal polyps were selected and stool specimens were taken. In addition, 24 healthy individuals were selected as control group. Extraction of bacterial DNA from the stool sample were performed. The molecular methods of PCR for confirmation of standard strain and absolute Real Time PCR (qRT-PCR) method were used to evaluate the number of Enterococcus faecalis in the studied groups. RESULTS: The results of this study indicate that the mean copy number of Enterococcus faecalis in patients with colorectal cancer was 11.2x109 per gram of stool, and in patients with polyps was 9.4x108 per gram of stool. In healthy people, this number was 9x108 per gram of stool. There was a significant difference between the implicit copy numbers in the three groups. (P<0.05). CONCLUSION: Enterococcus faecalis in faecal flora of people with colorectal cancer was significantly higher than those with polyps and healthy people. This could potentially signify the ability of this bacterium to induce colorectal cancer. More studies are needed to prove this theory.

Investigação da população de Enterococcus faecalis em pacientes com pólipo e câncer colorretal em comparação a indivíduos saudáveis / Investigation of enterococcus faecalis population in patients with polyp and colorectal cancer in comparison of healthy individuals

ABSTRACT BACKGROUND: Colorectal cancer is one of the most commonly diagnosed cancers around the world. One of the factors involved in the development of colorectal cancer is the changes in the normal flora of the intestine. OBJECTIVE: In this study, the mean copy number of Enterococcus faecalis in people with polyps and people with colorectal cancer has been evaluated in comparison with healthy controls. METHODS: In this study, 25 patients with colorectal cancer and 28 patients with intestinal polyps were selected and stool specimens were taken. In addition, 24 healthy individuals were selected as control group. Extraction of bacterial DNA from the stool sample were performed. The molecular methods of PCR for confirmation of standard strain and absolute Real Time PCR (qRT-PCR) method were used to evaluate the number of Enterococcus faecalis in the studied groups. RESULTS: The results of this study indicate that the mean copy number of Enterococcus faecalis in patients with colorectal cancer was 11.2x109 per gram of stool, and in patients with polyps was 9.4x108 per gram of stool. In healthy people, this number was 9x108 per gram of stool. There was a significant difference between the implicit copy numbers in the three groups. (P<0.05). CONCLUSION: Enterococcus faecalis in faecal flora of people with colorectal cancer was significantly higher than those with polyps and healthy people. This could potentially signify the ability of this bacterium to induce colorectal cancer. More studies are needed to prove this theory.

RESUMO CONTEXTO: O câncer colorretal é um dos cânceres mais comumente diagnosticados em todo o mundo. Um dos fatores envolvidos no desenvolvimento do câncer colorretal é a mudança na flora normal do intestino. OBJETIVO: O número médio de cópias de Enterococcus faecalis em pessoas com pólipos e pessoas com câncer colorretal foram avaliados em comparação com controles saudáveis. MÉTODOS: Neste estudo, 25 pacientes com câncer colorretal e 28 pacientes com pólipos intestinais foram selecionados e amostras de fezes foram adquiridas. Além disso, 24 indivíduos saudáveis foram selecionados como grupo controle. A extração do DNA bacteriano da amostra coletada foi executada. Os métodos moleculares de PCR para confirmação da cepa padrão e o método absoluto de PCR em tempo real (qRT-PCR) foram utilizados para avaliar o número de Enterococcus faecalis nos grupos estudados. RESULTADOS: Os resultados deste estudo indicam que o número médio de cópias de Enterococcus faecalis em pacientes com câncer colorretal foi de 11,2x109 por grama de fezes, e em pacientes com pólipos foi de 9,4x108 por grama de fezes. Em pessoas saudáveis, este número foi de 9x108 por grama de fezes. Houve diferença significativa entre os números de cópia implícita nos três grupos. (P<0,05). CONCLUSÃO: Enterococcus faecalis na flora fecal de pessoas com câncer colorretal foi significativamente maior do que aqueles com pólipos e pessoas saudáveis. Isto poderia potencialmente significar a capacidade desta bactéria para induzir o câncer colorretal. Mais estudos são necessários para provar esta teoria.

Moderate alteration to gut microbiota brought by colorectal adenoma resection.

BACKGROUND AND AIM: Microbial dysbiosis is involved in the development of colorectal cancer and its most common precancerous lesion, colorectal adenoma. Endoscopic resection is one of the procedures for primary prevention of colorectal cancer, yet little is known about how the endoscopic therapy influences gut microbiota. METHODS: We conducted a prospective study of 20 patients who underwent endoscopic resection of colorectal adenoma and analyzed the fecal microbiota before and 3 months after adenoma resection. MiSeq sequencing of 16S rRNA genes was performed to determine the alterations in microbial diversity and structure. To discriminate the microbiota of the two groups, random forest and receiver operating characteristic analysis were applied, and a genus-based microbiota signature was obtained. RESULTS: Despite few alterations in overall microbial structure after adenoma resection, the abundance of Parabacteroides revealed a significant increase postoperatively (3.8% vs 1.5%, 0.1160), and the microbiota signature of Parabacteroides, Streptococcus, and Ruminococcus showed an optimal discriminating performance of postoperative status with the area under the curve 0.788, P < 0.001. CONCLUSION: Fecal microbial alterations indicate the moderate influence of adenoma resection on gut microbiota and lay the groundwork for microbial prediction of adenoma recurrence. Larger sample studies are further required to validate the findings.

Potencial efeito preventivo do Lactobacillus acidophilus e Lactobacillus plantarum em pacientes com pólipos ou câncer colorretal / Potential preventive effect of lactobacillus acidophilus and lactobacillus plantarum in patients with polyps or colorectal câncer

ABSTRACT BACKGROUND: Colorectal cancer is one of the major causes of death worldwide. Many studies have been done on the biology of its formation as well as its treatment in recent years. One of the factors involved in the formation or treatment of this malignancy can be attributed to the microbial flora in the intestine. OBJECTIVE: This study investigate the potential preventive effect of Lactobacillus acidophilus and Lactobacillus plantarum in patients with polyps or colorectal cancer (CRC). METHODS: A total of 77 samples were selected in the form of three groups including individuals suffering from CRC, polyps and healthy subjects. Genomic DNA of fecal specimens and standard strains were extracted and amplified employing primers targeting of the 16S rRNA gene for initial detection. Absolute Real Time PCR quantification was used to determine the copy of the bacterial expression per gram of feces. RESULTS: No significant difference were observed between age and gender in the mentioned groups (P=0.06). The average copy number of Lactobacillus acidophilus shows Significant difference between the healthy group and those with polyps (P<0.0001), the healthy group and those with colorectal cancer (P<0.0001), as well as those with polyps and the colorectal cancer patients (P<0.0001). CONCLUSION: These results may indicate that taking Lactobacillus acidophilus in people with a family history of CRC and people with polyps may be a way of preventing, treating or reducing the severity of CRC.

RESUMO CONTEXTO: O câncer colorretal é uma das principais causas de morte em todo o mundo. Muitos estudos têm sido feitos sobre a biologia de sua formação, bem como o seu tratamento nos últimos anos. Um dos fatores envolvidos na formação ou no tratamento desta malignidade pode ser atribuído à flora microbiana no intestino. OBJETIVO: Este estudo investigou o potencial efeito preventivo de Lactobacillus acidophilus e Lactobacillus plantarum em pacientes com pólipos ou câncer colorretal (CCR). MÉTODOS: Um total de 77 amostras foram selecionadas e três grupos foram formados, a saber, indivíduos portadores de CCR, pólipos e indivíduos saudáveis. O DNA genomico de espécimes fecais e de amostras padrão foi extraído e amplificado empregando primers que focalizaram o gene do rRNA 16S para a deteção inicial. A quantificação do PCR em tempo real absoluto foi utilizada para determinar a cópia da expressão bacteriana por grama de fezes. RESULTADOS: Não foram observadas diferenças significativas entre idade e sexo nos grupos citados (P=0,06). O número médio de cópias de Lactobacillus acidophilus mostra diferença significativa entre o grupo saudável e aqueles com pólipos (P<0,0001), o grupo saudável e aqueles com câncer colorretal (P<0,0001), bem como aqueles com pólipos e câncer colorretal pacientes (P<0,0001). CONCLUSÃO: Estes resultados podem indicar que a ingestão de Lactobacillus acidophilus em pessoas com antecedentes familiares de CCR e pessoas com pólipos pode ser uma forma de prevenir, tratar ou reduzir a gravidade da CCR.

The association between fecal microbiota and different types of colorectal polyp as precursors of colorectal cancer.

BACKGROUND: Colon cancer (CRC) is a heterogeneous disorder, arising from precursors-adenoma and serrated polyp. Previous studies have demonstrated the relationship between the human gut microbiota and CRC; however, its correlation to the different early precursors of CRC is not properly understood. Here, we studied the relationship between targeted gut bacteria and different colorectal polyp types, location, size and grade of dysplasia. MATERIAL AND METHODS: In the present case-control descriptive study, selected fecal bacteria were assessed in 118 patients, referred for standard screening colonoscopy, including 31 normal controls, 21 hyperplastic polyp (HP), 16 sessile serrated polyp (SSA), 29 tubular adenoma (TA) and 21 villous/tubuvillous polyp (VP/TVP) cases, between 2015 and 2017, by absolute quantitative real time PCR technique (q PCR) in different ethnicity of Iranian population. The panel of bacteria was including Streptococcus bovis/gallolyticus, Enterococcus faecalis, Enterotoxigenic Bacteroides fragilis (ETBF), Fusobacterium nucleatum, Porphyromonas spp., Lactobacillus spp., Roseburia spp., and Bifidobacterium spp. RESULTS: Higher numbers of F. nucleatum, E. feacalis, S. bovis, ETBF and Porphyromonas spp. were detected in AP cases, consisting TA and especially VP/TVP, in contrast to samples from the normal, HP and SSA groups (P < 0.001). On the contrary, lower number of Lactobacillus spp., Roseburia spp. and Bifidobacterium spp. were detected in AP, compared to the normal, HP and SSA. Surprisingly, a significant correlation was found among selected gut bacterial quantity, the size, location and grade of dysplasia of polyp cases. DISCUSSION: These findings suggest that gut bacteria might contribute in early stages of colorectal carcinogenesis through the development of AP, but not SSA. In fact, AP and SSA are also different in terms of molecular pathways and tendencies to present in specific colorectal location. Overall, these findings may lead to development of CRC prevention therapies, targeting early protagonist bacteria of colorectal carcinogenesis from AP.

Dysbiosis-Associated Polyposis of the Colon-Cap Polyposis.

Cap polyposis is a rare gastrointestinal disease characterized by multiple inflammatory polyps located between the distal colon and the rectum. Despite the lack of clarity regarding its pathogenesis, mucosal prolapse, chronic inflammatory responses, and Helicobacter pylori infection are considered key contributors to the development of this disease entity. Although it is now generally accepted that dysbiosis of gut microbiota is associated with intestinal and extra-intestinal diseases, alterations of intestinal microbiota have been poorly defined in cap polyposis. Here, we report a patient with H. pylori-negative cap polyposis who was successfully treated with antibiotics and exhibited dramatic alterations in intestinal microbiota composition after antibiotic treatment. The patient was treated with oral administration of ampicillin and metronidazole and showed regression of cap polyposis 6 months after antibiotic treatment. Fecal microbiota analysis using the next-generation sequencing technology revealed a significant alteration in the intestinal microbiota composition following antibiotic treatment-a marked reduction of Blautia, Dorea, and Sutterella was observed concomitant with a marked increase in Fusobacterium. These data suggest that cap polyposis may originate from dysbiosis and that microbiome-targeted therapy may be useful in this disorder.

The oral microbiota in colorectal cancer is distinctive and predictive.

BACKGROUND AND AIMS: Microbiota alterations are linked with colorectal cancer (CRC) and notably higher abundance of putative oral bacteria on colonic tumours. However, it is not known if colonic mucosa-associated taxa are indeed orally derived, if such cases are a distinct subset of patients or if the oral microbiome is generally suitable for screening for CRC. METHODS: We profiled the microbiota in oral swabs, colonic mucosae and stool from individuals with CRC (99 subjects), colorectal polyps (32) or controls (103). RESULTS: Several oral taxa were differentially abundant in CRC compared with controls, for example, Streptococcus and Prevotellas pp. A classification model of oral swab microbiota distinguished individuals with CRC or polyps from controls (sensitivity: 53% (CRC)/67% (polyps); specificity: 96%). Combining the data from faecal microbiota and oral swab microbiota increased the sensitivity of this model to 76% (CRC)/88% (polyps). We detected similar bacterial networks in colonic microbiota and oral microbiota datasets comprising putative oral biofilm forming bacteria. While these taxa were more abundant in CRC, core networks between pathogenic, CRC-associated oral bacteria such as Peptostreptococcus, Parvimonas and Fusobacterium were also detected in healthy controls. High abundance of Lachnospiraceae was negatively associated with the colonisation of colonic tissue with oral-like bacterial networks suggesting a protective role for certain microbiota types against CRC, possibly by conferring colonisation resistance to CRC-associated oral taxa and possibly mediated through habitual diet. CONCLUSION: The heterogeneity of CRC may relate to microbiota types that either predispose or provide resistance to the disease, and profiling the oral microbiome may offer an alternative screen for detecting CRC.

Effects of probiotic bacteria on mucosal polyamines levels in dogs with IBD and colonic polyps: a preliminary study.

Spermine (SPM) and its precursor putrescine (PUT), regulated by ornithine decarboxylase (ODC) and diamino-oxidase (DAO), are polyamines required for cell growth and proliferation. Only a few studies have investigated the anti-inflammatory and tumour inhibitory properties of probiotics on mucosal polyamine levels. We investigated the effects of a high concentration multistrain probiotic for human use on colonic polyamine biosynthesis in dogs. Histological sections (inflammatory bowel disease, n=10; polyposis, n=5) were assessed after receiving 112 to 225×109 lyophilised bacteria daily for 60 days at baseline (T0) and 30 days after treatment end (T90). Histology scores, expression of PUT, SPM, ODC and DAO, and a clinical activity index (CIBDAI) were compared at T0 and T90. In polyps, cellular proliferation (Ki-67 expression), and apoptosis (caspase-3 protein expression) were also evaluated. After treatment, in inflammatory bowel disease significant decreases were observed for CIBDAI (P=0.006) and histology scores (P<0.001); PUT, SPM and ODC expression increased (P<0.01). In polyps, a significant decrease in polyamine levels, ODC activity, and Ki-67, and a significant increase in caspase-3 positivity and DAO expression (P=0.005) was noted. Our results suggest potential anti-proliferative and anti-inflammatory effects of the probiotic mixture in polyps and inflammation, associated with reduced mucosal infiltration and up-regulation of PUT, SPM, and ODC levels.

Macrophage depletion using clodronate liposomes decreases tumorigenesis and alters gut microbiota in the AOM/DSS mouse model of colon cancer.

We examined the role of macrophages in inflammation associated with colorectal cancer (CRC). Given the emerging evidence on immune-microbiota interactions in CRC, we also sought to examine the interaction between macrophages and gut microbiota. To induce CRC, male C57BL/6 mice ( n = 32) received a single injection of azoxymethane (AOM), followed by three cycles of dextran sodium sulfate (DSS)-supplemented water in weeks 1, 4, and 7. Prior to the final DSS cycle ( week 7) and twice weekly until euthanasia, mice ( n = 16/group) received either 200 µl ip of clodronate-filled liposomes (CLD) or phosphate-buffered saline (PBS) encapsulated liposomes to deplete macrophages. Colon tissue was analyzed for polyp burden, macrophage markers, transcription factors, and inflammatory mediators. Stool samples were collected, and DNA was isolated and subsequently sequenced for 16S rRNA. Clodronate liposomes decreased tumor number by ∼36% and specifically large (≥1 mm) tumors by ∼36% ( P < 0.05). This was consistent with a decrease in gene expression of EMR1 in the colon tissue and polyp tissue as well as expression of select markers associated with M1 (IL-6) and M2 macrophages (IL-13, IL-10, TGFß, CCL17) in the colon tissue ( P < 0.05). Similarly, there was a decrease in STAT3 and p38 MAPK and ERK signaling in colon tissue. Clodronate liposomes increased the relative abundance of the Firmicutes phylum ( P < 0.05) and specifically Lactobacillaceae and Clostridiaceae families, which have been associated with reduced CRC risk. Overall, these data support the development of therapeutic strategies to target macrophages in CRC and provide support for further evaluation of immune-microbiota interactions in CRC. NEW & NOTEWORTHY We found that macrophage depletion during late-stage tumorigenesis is effective at reducing tumor growth. This was associated with a decrease in macrophage markers and chemokines in the colon tissue and a decrease in transcription factors that are linked to colorectal cancer. The macrophage-depleted group was found to have an increased abundance of Firmicutes, a phylum with documented anti-tumorigenic effects. Overall, these data support the development of therapeutic strategies to target macrophages in colorectal cancer.

POTENTIAL PREVENTIVE EFFECT OF LACTOBACILLUS ACIDOPHILUS AND LACTOBACILLUS PLANTARUM IN PATIENTS WITH POLYPS OR COLORECTAL CÂNCER.

BACKGROUND: Colorectal cancer is one of the major causes of death worldwide. Many studies have been done on the biology of its formation as well as its treatment in recent years. One of the factors involved in the formation or treatment of this malignancy can be attributed to the microbial flora in the intestine. OBJECTIVE: This study investigate the potential preventive effect of Lactobacillus acidophilus and Lactobacillus plantarum in patients with polyps or colorectal cancer (CRC). METHODS: A total of 77 samples were selected in the form of three groups including individuals suffering from CRC, polyps and healthy subjects. Genomic DNA of fecal specimens and standard strains were extracted and amplified employing primers targeting of the 16S rRNA gene for initial detection. Absolute Real Time PCR quantification was used to determine the copy of the bacterial expression per gram of feces. RESULTS: No significant difference were observed between age and gender in the mentioned groups (P=0.06). The average copy number of Lactobacillus acidophilus shows Significant difference between the healthy group and those with polyps (P<0.0001), the healthy group and those with colorectal cancer (P<0.0001), as well as those with polyps and the colorectal cancer patients (P<0.0001). CONCLUSION: These results may indicate that taking Lactobacillus acidophilus in people with a family history of CRC and people with polyps may be a way of preventing, treating or reducing the severity of CRC.