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Comparative Genome Analysis of Fusobacterium nucleatum

Ang MY, Dutta A, Wee WY, Dymock D, Paterson IC, Choo SW

Genome Biol Evol, 2016 10 05;8(9):2928-2938.
PMID: 27540086

Fusobacterium nucleatum is considered to be a key oral bacterium in recruiting periodontal pathogens into subgingival dental plaque. Currently F. nucleatum can be subdivided into five subspecies. Our previous genome analysis of F. nucleatum W1481 (referred to hereafter as W1481), isolated from an 8-mm periodontal pocket in a patient with chronic periodontitis, suggested the possibility of a new subspecies. To further investigate the biology and relationships of this possible subspecies with other known subspecies, we performed comparative analysis between W1481 and 35 genome sequences represented by the five known Fusobacterium subspecies. Our analyses suggest that W1481 is most likely a new F. nucleatum subspecies, supported by evidence from phylogenetic analyses and maximal unique match indices (MUMi). Interestingly, we found a horizontally transferred W1481-specific genomic island harboring the tripartite ATP-independent (TRAP)-like transporter genes, suggesting this bacterium might have a high-affinity transport system for the C4-dicarboxylates malate, succinate, and fumarate. Moreover, we found virulence genes in the W1481 genome that may provide a strong defense mechanism which might enable it to colonize and survive within the host by evading immune surveillance. This comparative study provides better understanding of F. nucleatum and the basis for future functional work on this important pathogen.

Matched MeSH terms: Fusobacterium nucleatum/classification; Fusobacterium nucleatum/genetics*
Fulltext FusoBase: an online Fusobacterium comparative genomic analysis platform

Ang MY, Heydari H, Jakubovics NS, Mahmud MI, Dutta A, Wee WY, et al.

Database (Oxford), 2014;2014.
PMID: 25149689 DOI: 10.1093/database/bau082

Fusobacterium are anaerobic gram-negative bacteria that have been associated with a wide spectrum of human infections and diseases. As the biology of Fusobacterium is still not well understood, comparative genomic analysis on members of this species will provide further insights on their taxonomy, phylogeny, pathogenicity and other information that may contribute to better management of infections and diseases. To facilitate the ongoing genomic research on Fusobacterium, a specialized database with easy-to-use analysis tools is necessary. Here we present FusoBase, an online database providing access to genome-wide annotated sequences of Fusobacterium strains as well as bioinformatics tools, to support the expanding scientific community. Using our custom-developed Pairwise Genome Comparison tool, we demonstrate how differences between two user-defined genomes and how insertion of putative prophages can be identified. In addition, Pathogenomics Profiling Tool is capable of clustering predicted genes across Fusobacterium strains and visualizing the results in the form of a heat map with dendrogram.

Matched MeSH terms: Fusobacterium*
Liver abscess due to Fusobacterium species detected on ultrasonography: a case report

Subramaniyam V, Saito A, Tokushige K

J Med Ultrason (2001), 2018 Oct;45(4):623-627.
PMID: 29616359 DOI: 10.1007/s10396-018-0875-0

An oral infection harboring Fusobacterium species can gain entrance to the liver via hematogenous spread in the form of septic embolus, and can thereby cause abscesses. Such spread, described as Lemierre syndrome, is life threatening. We present such a case history of a man in his mid-40s, who presented with infection and Fusobacterium liver abscess with an acute fulminant disease course. The initial diagnosis was arrived at by ultrasound imaging and blood investigations. He was treated with antibiotics, ultrasound-guided liver abscess drainage, and extraction of the infected molar tooth. He was discharged 6 weeks after admission. To date, there have been no reports describing the ultrasound images of a Fusobacterium liver abscess in detail. Hence, we herein present the ultrasound images of a Fusobacterium liver abscess.

Matched MeSH terms: Fusobacterium Infections/therapy
Fulltext Antibody Responses to Fusobacterium nucleatum Proteins in Prediagnostic Blood Samples are not Associated with Risk of Developing Colorectal Cancer

Butt J, Jenab M, Pawlita M, Overvad K, Tjonneland A, Olsen A, et al.

Cancer Epidemiol Biomarkers Prev, 2019 Sep;28(9):1552-1555.
PMID: 31481495 DOI: 10.1158/1055-9965.EPI-19-0313

BACKGROUND: There is a lack of prospective data on the potential association of Fusobacterium nucleatum (F. nucleatum) and colorectal cancer risk. In this study, we assessed whether antibody responses to F. nucleatum are associated with colorectal cancer risk in prediagnostic serum samples in the European Prospective Investigation into Nutrition and Cancer (EPIC) cohort.
METHODS: We applied a multiplex serology assay to simultaneously measure antibody responses to 11 F. nucleatum antigens in prediagnostic serum samples from 485 colorectal cancer cases and 485 matched controls. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CI).
RESULTS: We observed neither a statistically significant colorectal cancer risk association for antibodies to individual F. nucleatum proteins nor for combined positivity to any of the 11 proteins (OR, 0.81; 95% CI, 0.62-1.06).
CONCLUSIONS: Antibody responses to F. nucleatum proteins in prediagnostic serum samples from a subset of colorectal cancer cases and matched controls within the EPIC study were not associated with colorectal cancer risk.
IMPACT: Our findings in prospectively ascertained serum samples contradict the existing literature on the association of F. nucleatum with colorectal cancer risk. Future prospective studies, specifically detecting F. nucleatum in stool or tissue biopsies, are needed to complement our findings.

Matched MeSH terms: Fusobacterium nucleatum/pathogenicity*
Fulltext Genome Sequence of Fusobacterium nucleatum Strain W1481, a Possible New Subspecies Isolated from a Periodontal Pocket

Ang MY, Dymock D, Tan JL, Thong MH, Tan QK, Wong GJ, et al.

Genome Announc, 2014;2(1).
PMID: 24526626 DOI: 10.1128/genomeA.00009-14

Fusobacterium nucleatum is a bacterial species commonly detected in dental plaque within the human oral cavity, with some strains associated with periodontal disease, one of the most common clinical bacterial infections in the human body. The exact mechanisms of its pathogenesis are still not completely understood. In this study, we present the genome sequence and annotation of F. nucleatum strain W1481, isolated from a periodontal pocket of a dental patient at the University of Bristol, United Kingdom, the 16S rRNA gene sequencing of which showed it to be markedly different from the five previously named subspecies.

Matched MeSH terms: Fusobacterium nucleatum
Fulltext Enrichment of gut-derived Fusobacterium is associated with suboptimal immune recovery in HIV-infected individuals

Lee SC, Chua LL, Yap SH, Khang TF, Leng CY, Raja Azwa RI, et al.

Sci Rep, 2018 09 24;8(1):14277.
PMID: 30250162 DOI: 10.1038/s41598-018-32585-x

We explored the gut microbiota profile among HIV-infected individuals with diverse immune recovery profiles following long-term suppressive ART and investigated the relationship between the altered bacteria with markers of immune dysfunction. The microbiota profile of rectal swabs from 26 HIV-infected individuals and 20 HIV-uninfected controls were examined. Patients were classified as suboptimal responders, sIR (n = 10, CD4 T-cell <350 cells/ul) and optimal responders, oIR (n = 16, CD4 T-cell >500 cells/ul) after a minimum of 2 years on suppressive ART. Canonical correlation analysis(CCA) and multiple regression modelling were used to explore the association between fecal bacterial taxa abundance and immunological profiles in optimal and suboptimal responders. We found Fusobacterium was significantly enriched among the HIV-infected and the sIR group. CCA results showed that Fusobacterium abundance was negatively correlated with CD4 T-cell counts, but positively correlated with CD4 T-cell activation and CD4 Tregs. Multiple linear regression analysis adjusted for age, baseline CD4 T-cell count, antibiotic exposure and MSM status indicated that higher Fusobacterium relative abundance was independently associated with poorer CD4 T-cell recovery following ART. Enrichment of Fusobacterium was associated with reduced immune recovery and persistent immune dysfunction following ART. Modulating the abundance of this bacterial taxa in the gut may be a viable intervention to improve immune reconstitution in our setting.

Matched MeSH terms: Fusobacterium/growth & development; Fusobacterium/immunology*
Fulltext Comparative evaluation of apical bacterial extrusion following root canal instrumentation using different endodontic file systems: An in vitro study

Vankayala B, Anantula K, Saladi H, Gudugunta L, Basavarajaiah JM, Yadav SS

J Conserv Dent, 2020 08 20;22(6):559-563.
PMID: 33088065 DOI: 10.4103/JCD.JCD_221_19

Aim: This study aims to evaluate the amount of apical extrusion of bacteria during root canal instrumentation using K3XF, Protaper Gold, Edge taper platinum, and Hyflex CM Rotary systems.
Materials and Methods: Sixty freshly extracted maxillary incisors teeth collected in saline. Access cavity prepared and canals were made free of bacterial and pulp. The teeth were mounted on the bacteria collecting apparatus. Root canals were contaminated with the Fusobacterium Nucleatum (ATCC25586) and dried at 37°C for 24 h. In Group 1 (Control group): No instrumentation was done and biomechanical preparation done in all other groups with Group 2: Hand K-files, Group 3: Protaper gold, Group 4: K3XF, Group 5: Edge taper platinum, and Group 6: Hyflex CM rotary file systems. Then, the extrude was collected, and it is incubated in Mueller-Hinton agar for 24 h and the number of colony forming units were counted and statistical comparison was done using Kruskal-Wallis test and Mann-Whitney U test.
Results: Hand K-files extruded more bacteria when compared to other four rotary systems, K3XF file system extruded least number of bacteria.
Conclusion: All instrumentation techniques extruded intracanal bacteria apically. However, engine-driven nickel-titanium instruments extruded less bacteria than the manual technique. The K3XF rotary file system comparatively extruded less bacteria than other rotary file systems.

Matched MeSH terms: Fusobacterium nucleatum
Fulltext Exposure to environmental microbiota explains persistent abdominal pain and irritable bowel syndrome after a major flood

Yusof N, Hamid N, Ma ZF, Lawenko RM, Wan Mohammad WMZ, Collins DA, et al.

Gut Pathog, 2017;9:75.
PMID: 29255490 DOI: 10.1186/s13099-017-0224-7

Background: After an environmental disaster, the affected community is at increased risk for persistent abdominal pain but mechanisms are unclear. Therefore, our study aimed to determine association between abdominal pain and poor water, sanitation and hygiene (WaSH) practices, and if small intestinal bacterial overgrowth (SIBO) and/or gut dysbiosis explain IBS, impaired quality of life (QOL), anxiety and/or depression after a major flood.
Results: New onset abdominal pain, IBS based on the Rome III criteria, WaSH practices, QOL, anxiety and/or depression, SIBO (hydrogen breath testing) and stools for metagenomic sequencing were assessed in flood victims. Of 211 participants, 37.9% (n = 80) had abdominal pain and 17% (n = 36) with IBS subtyped diarrhea and/or mixed type (n = 27 or 12.8%) being the most common. Poor WaSH practices and impaired quality of life during flood were significantly associated with IBS. Using linear discriminant analysis effect size method, gut dysbiosis was observed in those with anxiety (Bacteroidetes and Proteobacteria, effect size 4.8), abdominal pain (Fusobacteria, Staphylococcus, Megamonas and Plesiomonas, effect size 4.0) and IBS (Plesiomonas and Trabulsiella, effect size 3.0).
Conclusion: Disturbed gut microbiota because of environmentally-derived organisms may explain persistent abdominal pain and IBS after a major environmental disaster in the presence of poor WaSH practices.

Matched MeSH terms: Fusobacterium
Gut Microbiota and Epilepsy: A Systematic Review on Their Relationship and Possible Therapeutics

Arulsamy A, Tan QY, Balasubramaniam V, O'Brien TJ, Shaikh MF

ACS Chem Neurosci, 2020 Nov 04;11(21):3488-3498.
PMID: 33064448 DOI: 10.1021/acschemneuro.0c00431

Dysbiosis of gut microbiota may lead to a range of diseases including neurological disorders. Thus, it is hypothesized that regulation of the intestinal microbiota may prevent or treat epilepsy. The purpose of this systematic review is to evaluate the evidence investigating the relationship between gut microbiota and epilepsy and possible interventions. A systematic review of the literature was done on four databases (PubMed, Scopus, EMBASE, and Web of Science). Study selection was restricted to original research articles while following the PRISMA guidelines. Six studies were selected. These studies cohesively support the interaction between gut microbiota and epileptic seizures. Gut microbiota analysis identified increases in Firmicutes, Proteobacteria, Verrucomicrobia, and Fusobacteria with decreases in Bacteroidetes and Actinobacteria in epileptic patients. Ketogenic diet, probiotics, and fecal microbiota transplantation (FMT) improved the dysbiosis of the gut microbiota and seizure activity. However, the studies either had a small sample size, lack of subject variability, or short study or follow-up period, which may question their reliability. Nevertheless, these limited studies conclusively suggest that gut microbiota diversity and dysbiosis may be involved in the pathology of epilepsy. Future studies providing more reliable and in depth insight into the gut microbial community will spark promising alternative therapies to current epilepsy treatment.

Matched MeSH terms: Fusobacterium
Fulltext Targeting Gut Microbial Biofilms-A Key to Hinder Colon Carcinogenesis?

Chew SS, Tan LT, Law JW, Pusparajah P, Goh BH, Ab Mutalib NS, et al.

Cancers (Basel), 2020 Aug 13;12(8).
PMID: 32823729 DOI: 10.3390/cancers12082272

Colorectal cancer (CRC) is a global public health issue which poses a substantial humanistic and economic burden on patients, healthcare systems and society. In recent years, intestinal dysbiosis has been suggested to be involved in the pathogenesis of CRC, with specific pathogens exhibiting oncogenic potentials such as Fusobacterium nucleatum, Escherichia coli and enterotoxigenic Bacteroides fragilis having been found to contribute to CRC development. More recently, it has been shown that initiation of CRC development by these microorganisms requires the formation of biofilms. Gut microbial biofilm forms in the inner colonic mucus layer and is composed of polymicrobial communities. Biofilm results in the redistribution of colonic epithelial cell E-cadherin, increases permeability of the gut and causes a loss of function of the intestinal barrier, all of which enhance intestinal dysbiosis. This literature review aims to compile the various strategies that target these pathogenic biofilms and could potentially play a role in the prevention of CRC. We explore the potential use of natural products, silver nanoparticles, upconverting nanoparticles, thiosalicylate complexes, anti-rheumatic agent (Auranofin), probiotics and quorum-sensing inhibitors as strategies to hinder colon carcinogenesis via targeting colon-associated biofilms.

Matched MeSH terms: Fusobacterium nucleatum
Fulltext The expert says...... oral microbiology, periodontal disease and cardiovascular disease

Nor Adinar Baharuddin

Malaysian Dental Journal, 2007;28(2):97-98.
MyJurnal

There are evidences that chronic oral infections are associated with cardiovascular disease (CVD). Periodontal disease is a common, mixed oral infection affecting the supporting structures around the teeth. It was reported that 75% of the adult population has gingivitis and 20% to 30% exhibits the severe destructive form of periodontitis. Although more than 500 bacterial species inhabit the human oral cavity, only a few Gram negative bacteria such as Prevotella intermedia, Fusobacterium nucleatum, Porphyromonas gingivalis, Tannerella forsythensis, Treponema denticola and Actinobacillus actinomycetamcomitans causes gingivitis and periodontitis. These periodontal pathogen occupy the subgingival space and organize as a bacterial biofilm. The bacterial biofilm will be in direct contact with host tissues along an ulcerated epithelial interface, called periodontal pocket. The break in the epithelial integrity directly exposes the host to bacteria and their products eg. lipopolysaccharide (LPS) endotoxin. (Copied from article).

Matched MeSH terms: Fusobacterium nucleatum
Fulltext Predominant supragingival plaque microflora in a Malaysian population

Fathilah, A.R., Rahim, Z.H.A., Othman, Y.

Malaysian Dental Journal, 2007;28(2):92-96.
MyJurnal

The tooth provides a non-shedding surface ideal for microbial and plaque accumulation. Despite being exposed to regular environmental perturbations, the microbial composition and proportions in the plaque often remains in homeostasis and is relatively stable over time. Supragingival plaque sampled from various sites on the tooth surface was pooled and conventionally analyzed for its microbial constituent. Classification of microbial isolates was made based on the characteristics exhibited by the growth colonies, Gram-stained cells, as well as biochemical reactions using the API Identification System kit. Observation was also made of the colony forming units on both non-selective and selective agar culture plates. A variety of bacteria, both of the facultative and anaerobic types, were isolated from the supragingival plaque of the Malaysian population. Among those found to predominate the supragingival plaque include the Gram positive and Gram negative cocci and rods from the genera Streptococcus, Staphylococcus, Actinomyces, Fusobacterium, Corynebacterium, Clostridium, Bacteroides, Veilonella and Lactobacillus. In addition, yeast within the genus Candida was also isolated from the plaque samples.

Matched MeSH terms: Fusobacterium
Fulltext Antibacterial Activity of Myristica fragrans against Oral Pathogens

Shafiei Z, Shuhairi NN, Md Fazly Shah Yap N, Harry Sibungkil CA, Latip J

Evid Based Complement Alternat Med, 2012;2012:825362.
PMID: 23049613 DOI: 10.1155/2012/825362

Myristica fragrans Houtt is mostly cultivated for spices in Penang Island, Malaysia. The ethyl acetate and ethanol extracts of flesh, mace and seed of Myristica fragrans was evaluated the bactericidal potential against three Gram-positive cariogenic bacteria (Streptococcus mutans ATCC 25175, Streptococcus mitis ATCC 6249, and Streptococcus salivarius ATCC 13419) and three Gram-negative periodontopathic bacteria (Aggregatibacter actinomycetemcomitans ATCC 29522, Porphyromonas gingivalis ATCC 33277, and Fusobacterium nucleatum ATCC 25586). Antibacterial activities of the extracts was determined by twofold serial microdilution, with minimum inhibitory concentrations (MIC) ranging from 1.25 to 640 mg/mL and 0.075 to 40 mg/mL. The minimum bactericidal concentration (MBC) was obtained by subculturing method. Among all extracts tested, ethyl acetate extract of flesh has the highest significant inhibitory effects against Gram-positive and Gram-negative bacteria with mean MIC value ranging from 0.625 to 1.25 ± 0.00 (SD) mg/mL; P = 0.017) and highest bactericidal effects at mean MBC value ranging from 0.625 mg/mL to 20 ± 0.00 (SD) mg/mL. While for seed and mace of Myristica fragrans, their ethanol extracts exhibited good antibacterial activity against both groups of test pathogens compared to its ethyl acetate extracts. All of the extracts of Myristica fragrans did not show any antibacterial activities against Fusobacterium nucleatum ATCC 25586. Thus, our study showed the potential effect of ethyl acetate and ethanol extracts from flesh, seed and mace of Myristica fragrans to be new natural agent that can be incorporated in oral care products.

Matched MeSH terms: Fusobacterium nucleatum
Necrotizing Fasciitis on the Right Side of the Neck with Internal Jugular Vein Thrombophlebitis and Septic Emboli: A Case of Lemierre's-Like Syndrome

Nguyen D, Yaacob Y, Hamid H, Muda S

Malays J Med Sci, 2013 Oct;20(5):70-8.
PMID: 24643401

Lemierre's syndrome (LS) is a rare life-threatening infective condition typically starting with an oropharyngeal infection causing thrombophlebitis and metastatic abscesses. The most common aetiology of LS is Fusobacterium necrophorum; however, it can also occur after infection with other organisms. LS mainly affects young healthy adults. The initial infection site can be in the head and neck or in the abdomen. The morbidity rate of this disease is high despite aggressive treatments. In this article, we report a 63-year-old male patient with uncontrolled diabetes mellitus, presenting with Klebsiella pneumoniae infection-induced necrotizing fasciitis on the right side of the neck, leading to LS.

Matched MeSH terms: Fusobacterium necrophorum
Transcriptional responses of Streptococcus gordonii and Fusobacterium nucleatum to coaggregation

Mutha NVR, Mohammed WK, Krasnogor N, Tan GYA, Choo SW, Jakubovics NS

Mol Oral Microbiol, 2018 12;33(6):450-464.
PMID: 30329223 DOI: 10.1111/omi.12248

Cell-cell interactions between genetically distinct bacteria, known as coaggregation, are important for the formation of mixed-species biofilms such as dental plaque. Interactions lead to gene regulation in the partner organisms that may be critical for adaptation and survival in mixed-species biofilms. Here, gene regulation responses to coaggregation between Streptococcus gordonii and Fusobacterium nucleatum were studied using dual RNA-Seq. Initially, S. gordonii was shown to coaggregate strongly with F. nucleatum in buffer or human saliva. Using confocal laser scanning microscopy and transmission electron microscopy, cells of different species were shown to be evenly distributed throughout the coaggregate and were closely associated with one another. This distribution was confirmed by serial block face sectioning scanning electron microscopy, which provided high resolution three-dimensional images of coaggregates. Cell-cell sensing responses were analysed 30 minutes after inducing coaggregation in human saliva. By comparison with monocultures, 16 genes were regulated following coaggregation in F. nucleatum whereas 119 genes were regulated in S. gordonii. In both species, genes involved in amino acid and carbohydrate metabolism were strongly affected by coaggregation. In particular, one 8-gene operon in F. nucleatum encoding sialic acid uptake and catabolism was up-regulated 2- to 5-fold following coaggregation. In S. gordonii, a gene cluster encoding functions for phosphotransferase system-mediated uptake of lactose and galactose was down-regulated up to 3-fold in response to coaggregation. The genes identified in this study may play key roles in the development of mixed-species communities and represent potential targets for approaches to control dental plaque accumulation.

Matched MeSH terms: Fusobacterium nucleatum/physiology*
Fulltext Parvimonas micra, Peptostreptococcus stomatis, Fusobacterium nucleatum and Akkermansia muciniphila as a four-bacteria biomarker panel of colorectal cancer

Osman MA, Neoh HM, Ab Mutalib NS, Chin SF, Mazlan L, Raja Ali RA, et al.

Sci Rep, 2021 02 03;11(1):2925.
PMID: 33536501 DOI: 10.1038/s41598-021-82465-0

Dysbiosis of the gut microbiome has been associated with the pathogenesis of colorectal cancer (CRC). We profiled the microbiome of gut mucosal tissues from 18 CRC patients and 18 non-CRC controls of the UKM Medical Centre (UKMMC), Kuala Lumpur, Malaysia. The results were then validated using a species-specific quantitative PCR in 40 CRC and 20 non-CRC tissues samples from the UMBI-UKMMC Biobank. Parvimonas micra, Fusobacterium nucleatum, Peptostreptococcus stomatis and Akkermansia muciniphila were found to be over-represented in our CRC patients compared to non-CRC controls. These four bacteria markers distinguished CRC from controls (AUROC = 0.925) in our validation cohort. We identified bacteria species significantly associated (cut-off value of > 5 fold abundance) with various CRC demographics such as ethnicity, gender and CRC staging; however, due to small sample size of the discovery cohort, these results could not be further verified in our validation cohort. In summary, Parvimonas micra, Fusobacterium nucleatum, Peptostreptococcus stomatis and Akkermansia muciniphila were enriched in our local CRC patients. Nevertheless, the roles of these bacteria in CRC initiation and progression remains to be investigated.

Matched MeSH terms: Fusobacterium nucleatum/isolation & purification
Fulltext Microbiome and colorectal cancer: an overview and local perspective

Rahman Jamal

Malaysian Journal of Medicine and Health Sciences, 2019;15(108):4-4.
MyJurnal

Colorectal cancer (CRC) is an important health problem that is on the rise globally, where it is the fourth most com-mon cause of deaths from cancer. CRC is now the 2nd commonest cancer in men and 3rd commonest in women in Malaysia. Diet, lifestyle, genetics and environmental interaction, together with underlying gut conditions such as inflammatory bowel disease have been reported to contribute to the disease. In addition, the gut microbiome has also been increasingly reported to be associated with CRC development, with dysbiosis of the commensal bacteria ob-served in CRC patients. Bacterial genera such as Bacteroides, Fusobacterium and Prevotella are more commonly de-tected in CRC patients compared to healthy individuals. Nevertheless, not much is known about the gut microbiome among Malaysians with different ethnicities. In Malaysia, the Chinese has the highest incidence of CRC, followed by Malays and Indians. The reason behind this difference may be contributed by the differences in the dietary intake that could modulate the gut microbiome and contribute towards the development of CRC. The current knowledge on this field still much depends on reports from individuals of American, European, Chinese, Brazilian and Japanese descendants in origin. The oncogenic potential of bacteria was suggested to include inflammation and the produc-tion of mutagenic toxin. A significant increase in certain intestinal microbiota including the genuses Enteroccus and Streptococcus spp. was detected in the advanced stage of colorectal adenoma. However, there are discrepancies in the previous studies, where some bacteria genera might be over-reported or underestimated. It is likely that the gut microbiome differs between populations. There is also no available data on the gut microbiome of the healthy individuals, colorectal adenoma (pre-cancerous) and colorectal cancer patients in the Malaysian population. Recent advancements in next generation sequencing allow faster and more accurate determination of microbial consortium in various niches of the human body and environment. In particular, sequencing of the 16S rRNA gene with specific primers have been reported to allow accurate determination of bacterial orders commonly found in the human gut as well as for those which are not expected in the digestive system. Recent developments in gut microbiome DNA ex-traction also contributed to the robustness of gut microbiome determination and analysis. All the above will contrib-ute towards an accurate and rapid cataloging process of the Malaysian gut microbiome and also enable comparison between healthy individuals, colorectal adenoma and CRC patients of the Malaysian population.

Matched MeSH terms: Fusobacterium
Fulltext Salivary bacterial shifts in oral leukoplakia resemble the dysbiotic oral cancer bacteriome

Gopinath D, Kunnath Menon R, Chun Wie C, Banerjee M, Panda S, Mandal D, et al.

J Oral Microbiol, 2020 Dec 09;13(1):1857998.
PMID: 33391629 DOI: 10.1080/20002297.2020.1857998

Objective: While some oral carcinomas appear to arise de novo, others develop within long-standing conditions of the oral cavity that have malignant potential, now known as oral potentially malignant disorders (OPMDs). The oral bacteriome associated with OPMD has been studied to a lesser extent than that associated with oral cancer. To characterize the association in detail we compared the bacteriome in whole mouth fluid (WMF) in patients with oral leukoplakia, oral cancer and healthy controls. Methods: WMF bacteriome from 20 leukoplakia patients, 31 patients with oral cancer and 23 healthy controls were profiled using the Illumina MiSeq platform. Sequencing reads were processed using DADA2, and taxonomical classification was performed using the phylogenetic placement method. Sparse Partial Least Squares Regression Discriminant Analysis model was used to identify bacterial taxa that best discriminate the studied groups. Results: We found considerable overlap between the WMF bacteriome of leukoplakia and oral cancer while a clearer separation between healthy controls and the former two disorders was observed. Specifically, the separation was attributed to 14 taxa belonging to the genera Megaspheara, unclassified enterobacteria, Prevotella, Porphyromonas, Rothia and Salmonella, Streptococcus, and Fusobacterium. The most discriminative bacterial genera between leukoplakia and oral cancer were Megasphaera, unclassified Enterobacteriae, Salmonella and Prevotella.Conclusion: Oral bacteria may play a role in the early stages of oral carcinogenesis as a dysbiotic bacteriome is associated with oral leukoplakia and this resembles that of oral cancer more than healthy controls. Our findings may have implications for developing oral cancer prevention strategies targeting early microbial drivers of oral carcinogenesis.

Matched MeSH terms: Fusobacterium
Fulltext High-resolution bacterial 16S rRNA gene profile meta-analysis and biofilm status reveal common colorectal cancer consortia

Drewes JL, White JR, Dejea CM, Fathi P, Iyadorai T, Vadivelu J, et al.

NPJ Biofilms Microbiomes, 2017;3:34.
PMID: 29214046 DOI: 10.1038/s41522-017-0040-3

Colorectal cancer (CRC) remains the third most common cancer worldwide, with a growing incidence among young adults. Multiple studies have presented associations between the gut microbiome and CRC, suggesting a link with cancer risk. Although CRC microbiome studies continue to profile larger patient cohorts with increasingly economical and rapid DNA sequencing platforms, few common associations with CRC have been identified, in part due to limitations in taxonomic resolution and differences in analysis methodologies. Complementing these taxonomic studies is the newly recognized phenomenon that bacterial organization into biofilm structures in the mucus layer of the gut is a consistent feature of right-sided (proximal), but not left-sided (distal) colorectal cancer. In the present study, we performed 16S rRNA gene amplicon sequencing and biofilm quantification in a new cohort of patients from Malaysia, followed by a meta-analysis of eleven additional publicly available data sets on stool and tissue-based CRC microbiota using Resphera Insight, a high-resolution analytical tool for species-level characterization. Results from the Malaysian cohort and the expanded meta-analysis confirm that CRC tissues are enriched for invasive biofilms (particularly on right-sided tumors), a symbiont with capacity for tumorigenesis (Bacteroides fragilis), and oral pathogens including Fusobacterium nucleatum, Parvimonas micra, and Peptostreptococcus stomatis. Considered in aggregate, species from the Human Oral Microbiome Database are highly enriched in CRC. Although no detected microbial feature was universally present, their substantial overlap and combined prevalence supports a role for the gut microbiota in a significant percentage (>80%) of CRC cases.

Matched MeSH terms: Fusobacterium nucleatum
Fulltext Composition and Antibacterial Activity of the Essential Oils of Orthosiphon stamineus Benth and Ficus deltoidea Jack against Pathogenic Oral Bacteria

Azizan N, Mohd Said S, Zainal Abidin Z, Jantan I

Molecules, 2017 Dec 05;22(12).
PMID: 29206142 DOI: 10.3390/molecules22122135

In this study, the essential oils of Orthosiphon stamineus Benth and Ficus deltoidea Jack were evaluated for their antibacterial activity against invasive oral pathogens, namely Enterococcus faecalis, Streptococcus mutans, Streptococcus mitis, Streptococcus salivarius, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Fusobacterium nucleatum. Chemical composition of the oils was analyzed using gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). The antibacterial activity of the oils and their major constituents were investigated using the broth microdilution method (minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC)). Susceptibility test, anti-adhesion, anti-biofilm, checkerboard and time-kill assays were also carried out. Physiological changes of the bacterial cells after exposure to the oils were observed under the field emission scanning electron microscope (FESEM). O. stamineus and F. deltoidea oils mainly consisted of sesquiterpenoids (44.6% and 60.9%, respectively), and β-caryophyllene was the most abundant compound in both oils (26.3% and 36.3%, respectively). Other compounds present in O. stamineus were α-humulene (5.1%) and eugenol (8.1%), while α-humulene (5.5%) and germacrene D (7.7%) were dominant in F. deltoidea. The oils of both plants showed moderate to strong inhibition against all tested bacteria with MIC and MBC values ranging 0.63-2.5 mg/mL. However, none showed any inhibition on monospecies biofilms. The time-kill assay showed that combination of both oils with amoxicillin at concentrations of 1× and 2× MIC values demonstrated additive antibacterial effect. The FESEM study showed that both oils produced significant alterations on the cells of Gram-negative bacteria as they became pleomorphic and lysed. In conclusion, the study indicated that the oils of O. stamineus and F. deltoidea possessed moderate to strong antibacterial properties against the seven strains pathogenic oral bacteria and may have caused disturbances of membrane structure or cell wall of the bacteria.

Matched MeSH terms: Fusobacterium nucleatum/drug effects; Fusobacterium nucleatum/growth & development; Fusobacterium nucleatum/isolation & purification

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