Anaerobic bacteria, including Bacteroides spp., usually reside in the lower intestinal tract as indigenous bacteria. However, they are sometimes detected as pathogens in infectious disease patients. Anaerobe infection can be highly lethal and life threatening, and its mortality rate is estimated to be as high as 40% . Therefore, it is crucial to identify pathogenic bacteria immediately and initiate appropriate antibiotic therapy targeting the identified specific pathogen. In the last decade, in addition to conventional culture tests, MALDI-TOF MS has been widely used for clinical examination. This method is capable of detecting pathogens in a few minutes after applying samples, but this mass spectrum-based bacterial identification has some limitations among bacteria having similar protein compositions or uncommon bacterial species, partially due to incomplete reference databases. Because of only 5% gene sequence divergence between B. dorei and B. vulgatus , two major MALDI-TOF MS systems commercially available misidentify B. dorei as B. vulgatus or cannot distinguish them [12, 13]. Our facility also employs the MALDI-TOF MS system for the identification of pathogens and could not discriminate between B. dorei and B. vulgatus, determining the pathogen as "B. vulgatus/dorei" in this case.
16S rRNA gene sequencing is a highly potent molecular biological approach for identifying specific bacteria to the species level, particularly in the case of uncommon, slow-growing or uncultivable bacteria, such as minor anaerobes. Due to the inexpensiveness and easy availability of PCR and DNA sequencing needed for this method, it has been a complementary examination tool for the accurate identification of bacteria and the discovery of novel bacterial species in clinical and laboratory settings . In 2019, J. S. Johnson et al. reported the interspecies sequence entropy of the 16S rRNA gene, depicting that the V2, V3, V6, and V9 regions had relatively high sequence variations and noted the validity of sub-regional sequencing for discriminating closely related bacteria from specific taxa . As preliminary experiments, we initially amplified the full, first-half and second-half lengths of the 16S rRNA gene sequence, and thereby, it was shown that the second-half sequence was prone to more effective amplification and that amplicon sequencing could identify specific bacteria satisfactorily (data not shown). In this case, through amplification and sequencing of the V5-V9 segments, we successfully identified B. dorei as a pathogen with 100% sequence identity. Altogether, it was corroborated that partial 16S rRNA gene sequencing, which included at least two of the four high variant regions mentioned above, has sufficient detectability and capability of discriminating specific bacteria among allied species.
Under this sequencing-based bacterial identification, the pathophysiology of B. dorei has been gradually uncovered. When we searched the PubMed database using the keyword "Bacteroides dorei", only 50 articles were published by June 1st, 2020. It is seemingly innocuous in healthy individuals, as Bacteroidetes and Firmicutes constitute over 90% of healthy gut microbial assemblage . However, it has been demonstrated that the B. dorei proportion in the gut microbiota is responsible for a variety of diseases, including autoimmune type 1 diabetes mellitus [9, 17–22], colorectal diseases [23–26], atherosclerotic diseases [27–30], and even Parkinson's disease . On the other hand, there is almost no report regarding B. dorei as a cause of infectious diseases or even a part of its contagious process, which consists of tissue invasion, multiplication and colonisation and infliction of host tissue damage by cytotoxic materials or direct interactions. In immunocompromised or dysbiosis states resulting in a permeable gut and impairment of mucosal barriers, pathogens may invade nearby tissues or the systemic circulation, consequently initiating infectious diseases. Despite the assumption of these mechanisms, there is no sufficient evidence for understanding the pathogenesis of B. dorei. As a result, this report describes the first case of invasive infectious disease caused by B. dorei. Further studies are needed to elucidate its infectious processes.
The association of dysbacteriosis or alteration of the B. dorei proportion in the gut microbiota with these diseases might be a target for preventative or therapeutic interventions. Some researchers have proposed using some indigenous bacteria as pre-/probiotics for modulating gut bacterial composition, including B. dorei itself [10, 29, 30, 32–35]. However, as microbiome composition is influenced by daily meals, eating habits and geography and temporally varies even in individuals, the efficacy of probiotic usage may be definite in a specific condition. Furthermore, as the gut microbiota forms complex systems (e.g., metabolic network, interaction with an immune system or inter-microbial interaction), the effect of modification of specific bacterial abundance is not necessarily predictable . Moreover, due to its invasive potential causing infectious diseases, such as in this case report, considerable attention must be paid to the use of B. dorei as a probiotic. Additional studies regarding the application of probiotics or modulating strategies of the gut microbiota are needed.
The metabolic profile of B. dorei has also been studied and has shown its uniqueness [37–41]. To date, only two bacteria have been identified with cholesterol-reducing capacity in a human microbial community, Eubacterium coprostanoligenes and B. dorei strain D8 [42, 43], which is proposed to have protective roles for atherosclerosis. However, this report presented a case of an infected aortic aneurysm caused by B. dorei detected from a surgically dissected atherosclerotic lesion. This contradictory aspect can be partially explained by the microbial metabolic features described in one report in which Bacteroides thetaiotaomicron was shown to selfishly or exclusively metabolise yeast mannan . These results may imply that some bacteria have preferences for a specific tissue site, such as atherosclerotic lesions or microbial community sites. As B. dorei strains have the potential to metabolise cholesterol, they may be predisposed to colonise atherosclerotic tissues with plaque deposited by fat, cholesterol and calcium. Therefore, B. dorei potentially causes a mycotic aneurysm or infective endocarditis in atherosclerotic patients. This fact also gives us warning regarding the utilisation of B. dorei as a biotherapeutic tool, particularly in the form of live bacteria.
In conclusion, we report the first case of invasive infectious disease by B. dorei in a mycotic thoracic aneurysm patient, which disagrees with the protective roles of B. dorei in atherosclerotic diseases.