Background and Objectives: The incidence of metabolic dysfunction-associated steatohepatitis (MASH)-related hepatocellular carcinoma (HCC) is increasing worldwide, alongside the epidemic of obesity and metabolic syndrome. Based on preliminary reports regarding the potential association of HCC and periodontitis, this study aimed to analyze the involvement of periodontal bacteria as well as the oral and intestinal bacterial flora in MASH-related HCC (MASH-HCC). Materials and Methods: Forty-one patients with MASH and nineteen with MASH-HCC participated in the study, completing survey questionnaires, undergoing periodontal examinations, and providing samples of saliva, mouth-rinsed water, feces, and peripheral blood. The oral and fecal microbiome profiles were analyzed by 16S ribosomal RNA sequencing. Bayesian network analysis was used to analyze the causation between various factors, including MASH-HCC, examinations, and bacteria. Results: The genus Fusobacterium had a significantly higher occupancy rate (p = 0.002) in the intestinal microflora of the MASH-HCC group compared to the MASH group. However, Butyricicoccus (p = 0.022) and Roseburia (p < 0.05) had significantly lower occupancy rates. The Bayesian network analysis revealed the absence of periodontal pathogenic bacteria and enteric bacteria affecting HCC. However, HCC directly affected the periodontal bacterial species Porphyromonas gingivalis, Tannerella forsythia, Fusobacterium nucleatum, and Prevotella intermedia in the saliva, as well as the genera Lactobacillus, Roseburia, Fusobacterium, Prevotella, Clostridium, Ruminococcus, Trabulsiella, and SMB53 in the intestine. Furthermore, P. gingivalis in the oral cavity directly affected the genera Lactobacillus and Streptococcus in the intestine. Conclusions: MASH-HCC directly affects periodontal pathogenic and intestinal bacteria, and P. gingivalis may affect the intestinal bacteria associated with gastrointestinal cancer.

Background and Objectives: Anaerobic bacteria like Fusobacterium can lead to severe and life-threatening infections. The inherent complexities in the isolation of these bacteria may result in diagnostic and therapeutic delays, thereby escalating both morbidity and mortality rates. We aimed to examine data from patients with infections due to Fusobacterium to gain insights into the epidemiology and clinical outcomes of patients with these infections. Methods and Results: We conducted a retrospective analysis of clinical data from a cohort of patients with cultures positive for Fusobacterium species at a tertiary care medical center in the United States. Between 2009 and 2015, we identified 96 patients with cultures positive for Fusobacterium. Patients could be categorized into three groups based on the site of primary infection. Patients with head and neck infections constituted 37% (n 36). Patients with infections of other soft tissue sites accounted for 38.5% (n 37). Patients with anaerobic bacteremia due to Fusobacterium formed 24% (n 23) of the cohort. Surgical intervention coupled with antibiotic therapy emerged as cornerstones of management for patients with head and neck or other soft tissue infections, who generally exhibited more favorable outcomes. Patients with bacteremia were older, more likely to have malignancy, and had a high mortality rate. When speciation was available, Fusobacterium necrophorum was the most frequently isolated species. Conclusions: Our retrospective analysis of epidemiology and clinical outcomes of Fusobacterium infections revealed three distinct cohorts. Patients with head, neck, or soft tissue infections had better outcomes than those with bacteremia. Our findings highlight the importance of employing management strategies based on infection site and underlying comorbidities in patients with Fusobacterium infections. Further research is needed to investigate the optimal therapeutic strategies and identify prognostic indicators to improve clinical outcomes for these complex infections.

OBJECTIVE: We aimed to explore the impact of social distancing on the incidence and microbiology of peritonsillar abscess (PTA).
METHODS: We performed a cross-sectional analysis of all patients with PTA and their microbiological findings in the 2 years preceding versus the 2 years following the COVID-19 lockdown in Denmark (11 March 2020), who were admitted to the Ear-Nose-Throat Department, Aarhus University Hospital. Age-stratified population data for the catchment area were obtained from Statistics Denmark.
RESULTS: The annual incidence rate was significantly higher in the 2-year period before (21.8 cases/100 000 inhabitants) compared with after (14.9 cases/100 000) the lockdown (p < 0.001). The number of cases with growth of Streptococcus pyogenes was significantly higher in the period before (n = 67) compared with after (n = 28) the lockdown (p < 0.001), whereas the number of cases positive for Fusobacterium necrophorum (n = 60 vs. n = 64) and streptococcus anginosus group (SAG) (n = 37 vs. n = 43) were stabile (p 0.79 and p 0.58, respectively). The relative prevalence of S. pyogenes was significantly higher in the period before (67/246 cultures, 27%) compared with after (28/179, 16%) the lockdown (p 0.007). On the contrary, the relative prevalence of F. necrophorum and SAG is significantly lower before (60/246, 24% and 37/246, 15%) compared with after (64/179, 36% and 43/179, 24%) the lockdown (p 0.013 and p 0.023).
CONCLUSIONS: Social distancing had a significant impact on the incidence and microbiology of PTA. Our findings suggest that S. pyogenes-positive PTA is highly related to direct social interaction, and represents a contagious pathogen. By contrast, PTA development caused by F. necrophorum and SAG is unrelated to direct social interaction and may be derived from flora imbalance.

OBJECTIVE: The present study aims to investigate the variations in dental caries (DC) related microbiome abnormality and metabolomics shift in children.
METHODS: The patients were divided into two groups healthy control (C) and highly affected DC children based on inclusion and exclusion criteria. Saliva samples were collected and used for the taxonomic and functional characterization of oral microbiota.
RESULTS: Metatranscriptomics analysis revealed the alterations and composition of oral microbiota in the C and DC groups. Relative abundance in the C group was associated with Firmicutes, Actinobacteria, and Bacteroidetes. Whereas, the microbial composition in the DC group was found to be considerably altered with increases in the abundance of the Proteobacteria (25%), Fusobacteria (15%), and Cyanobacteria (8%) while decreases in the abundance of Firmicutes (10%) and Bacteroidetes (23%). Alterations in the phylum composition were positively and negatively correlated with several metabolites of sugars (such as fructose, sorbose, ribose, allose, and mannose) and amino acids (such as arginine, lysine, tryptophan, and proline). Moreover, in comparison with the C group, the metabolic shift of the DC group was different with an increase in certain tricarboxylic acid cycle intermediates levels, and a decrease in fatty acid. Such alterations can enhance the growth of oral pathogens and contribute to DC development.
CONCLUSIONS: The findings of this study suggest that an altered abundance of Actinobacillus, Fusobacterium, and Shuttleworthia can serve as biomarkers of DC in children.

Matcha green tea is made from powdered green tea leaves. Unlike regular green tea, Matcha green tea is believed to exert beneficial effects on the gut microbiota, as it is richer in nutrients such as tea catechins and insoluble dietary fiber. In the present study, we aimed to investigate the effects of consumption of Matcha green tea on the gut microbiota. Human participants were randomly assigned to a placebo (n = 16) or a Matcha green tea (n = 17) drink group and asked to drink the treatments for two weeks. Feces were collected from the participants pre- and post-treatment and fecal microbiota composition was analyzed by 16S rRNA metagenomic sequencing. The beta-diversity of microbial composition significantly (p<0.05) changed in MGT group but not in placebo group. In addition, the number of unique bacterial genera significantly (p<0.05) changed in the Matcha green tea group was 30, while it was only 3 in the Placebo group. Increase and decrease in abundances of Coprococcus and Fusobacterium, respectively, in the gut microbiota of Matcha green tea group, conferred potential health benefits to the host. The present study was registered in the UMIN Clinical Trial Registry (UMIN000043857).

Colorectal cancers (CRCs) with deficient DNA mismatch repair (dMMR) and proficient DNA mismatch repair (pMMR) exhibit heterogeneous tumor characteristics, distinct responses to immunotherapy, and different survival outcomes. However, it is unclear whether gut microbiota is distinct between CRCs with different MMR status. In this study, we used immunohistochemistry for four major MMR proteins to determine the MMR status in 230 CRC patients. The gut microbiota was profiled in cancerous and adjacent normal tissues by using bacterial 16S rRNA sequencing. The differences in microbiota diversity, composition and related metabolic pathways between patients with dMMR and pMMR CRCs were explored. Linear discriminant analysis effect size (LEfSe) analysis was further applied to validate the significant taxonomic differences at the genus level. In our study cohort, dMMR status was identified in 29 of 230 (12.61%) tumors. The richness (alpha-diversity) of gut microbiome in dMMR tumor tissue was higher compared with pMMR tumor tissues. The microbial community composition (beta-diversity) between the two groups was significantly different. The dMMR group was enriched considerably for some microbiota, including Fusobacteria, Firmicutes, Verrucomicrobia, and Actinobacteria at the phylum level and Fusobacterium, Akkermansia, Bifidobacterium, Faecalibacterium, Streptococcus, and Prevotella bacteria at the genus level. However, the pMMR group was dominated by Proteobacteria at the phylum level and Serratia, Cupriavidus and Sphingobium at the genus level. Moreover, a wide variety of microbiota associated functional pathways were observed with different MMR status. KEGG pathway analysis indicated a higher abundance of the biosynthesis and metabolic pathways of glycan and nucleotide, cell growth and death pathways, genetic replication and repair pathways in dMMR samples compared with the pMMR group. These findings demonstrate that CRC patients with different MMR status have distinct gut bacterial community richness, compositions and related metabolic pathways, suggesting basis that may explain the effectiveness of immunotherapy in dMMR tumors.

OBJECTIVE: The study by the method of tissue polymerase chain reaction of the species composition of the microbiota of lesions of the oral mucosa in patients with bullous lesions.
METHODS: Biopsy specimens of the oral mucosa of 51 patients were studied by the polymerase chain reaction method, of which 14 patients with pemphigus vulgaris, 17 patients with pemphigoid bullosa, and 20 patients with the bullous form of ruber lichen planus. 4 types of microorganisms have been identified - Fusobacterium, Streptococcus pneumoniae, Candida albicans, Ureaplasma spp. and viruses - Human Papillomavirus 16, Epstein-Barr virus and Citomegalovirus.
RESULTS: In the study of the microbiota of bullous lesions, associations of microorganisms and viruses were established in a significant number of cases. Associations of Str.pneumoniae and C. albicans were quite common in patients with pemphigus vulgaris in 26.3%, pemphigoid bullosa in 20.0%, and in patients with the bullous form of ruber lichen planus in 14.3% of cases. In patients with pemphigus vulgaris, the association of Str.pneumoniae, C. albicans and EBV was noted in 31.6% of cases. In patients with the bullous form of ruber lichen planus in a high percentage of cases (28.6%), the associations of Str. pneumoniae, EBV and CMV.
CONCLUSIONS: Identification at earlier stages of management of patients with bullous lesions Str. pneumoniae, Candida albicans, and Fusobacterium associated with herpes viruses should be regarded as one of the triggering mechanisms of an autoimmune conflict, which subsequently causes a specific clinical picture of these diseases.
UNASSIGNED: Изучение методом тканевой полимеразной цепной реакции (ПЦР) видового состава микробиоты очагов поражения слизистой оболочки рта у пациентов с буллезными поражениями.
UNASSIGNED: Методом ПЦР исследованы биоптаты слизистой оболочки рта 51 пациента, из них 14 с pemphigus vulgaris, 17 с pemphigoid bullosa и 20 с буллезной формой ruber lichen planus. Определены 4 вида микроорганизмов — Fusobacterium, Streptococcus pneumoniae, Candida albicans, Ureaplasma spp. и вирусы — Human Papillomavirus 16, Epstein—Barr virus (EBV) и Citomegalovirus (CMV).
UNASSIGNED: При исследовании микробиоты буллезных поражений в значительном числе случаев установлены ассоциации микроорганизмов и вирусов. Ассоциации Str. pneumoniae и C. albicans встречались достаточно часто: у пациентов с pemphigus vulgaris в 26,3% случаев, с pemphigoid bullosa — в 20,0%, у пациентов с буллезной формой ruber lichen planus — в 14,3% случаев. У больных с pemphigus vulgaris в 31,6% случаев отмечена ассоциация Str. pneumoniae, C. albicans и EBV. У пациентов с буллезной формой ruber lichen planus в 28,6% случаев выделены ассоциации Str. pneumoniae, EBV и CMV.
UNASSIGNED: Выявление на ранних этапах ведения больных с буллезными поражениями Str. pneumoniae, C. albicans и Fusobacterium, ассоциированных с герпетическими вирусами, следует расценивать как один из пусковых механизмов аутоиммунного конфликта, вызывающего в появление специфической клинической картины данных заболеваний.

The past decade has witnessed a rise in Fusobacterium infections. This study aimed to describe the epidemiology, clinical and demographic characteristics and outcomes associated with Fusobacterium infections in hospitalized children in central Israel.
We retrospectively analyzed the medical records of children <18 years old who had been admitted with a diagnosis of invasive Fusobacterium infection (IFI) between January 2010 and April 2020. Clinical, laboratory and microbiologic data were retrieved. IFI diagnosis was based upon microbiological identification in any specimen by culture or by 16S ribosomal RNA polymerase chain reaction.
Fifty-one children (26 boys) with a median age of 3 years (range, 5-16 years) were included. Hospitalizations for IFI increased from 19 of 100,000 admissions between 2010 and 2015 to 50 of 100,000 between 2016 and 2020, representing a 2.5-fold increase. Most of the infections were from an otogenic source (n = 28, 55%) followed by an oropharyngeal/respiratory source (n = 21, 41%). The most common complications were subperiosteal and epidural abscesses (41% and 37%, respectively). Thrombosis was diagnosed in 11 children, 10 of whom had sinus vein thrombosis. All had an otogenic source. Children with otogenic compared with all other infection sources were significantly younger (median age of 1.9 vs. 3 years; P < 0.001). Forty-seven children (92%) underwent a surgical intervention. All patients survived, one with neurologic sequelae.
The admissions for IFI in children increased 2.5-fold during the last decade. The most common source is otogenic, especially among younger children, and it is associated with high complication rates. Current management, including combinations of antibiotics and surgical interventions, leads to favorable outcome.

OBJECTIVE: To study the spectrum of anaerobic infections and the frequency of clinically relevant anaerobes in various infections in a tertiary care hospital in North India.
METHODS: In this two-year (2018-2019) retrospective study, a total of 22,177 samples were processed both anaerobically and aerobically. The samples included blood, pus, body fluids, necrotic tissues, abscess, peritoneal fluids, and other specimens of conditions predisposing to anaerobic infections. The recovered bacterial isolates were identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS).
RESULTS: Of the 22,177 samples processed anaerobically, 1094 showed significant anaerobic growth yielding 1464 anaerobes. Bacteroides fragilis (12.7%) and Peptoniphilus harei (12.2%) were the most predominant anaerobes, whereas Escherichia coli (32.6%) and Staphylococcus aureus (13.2%) were the most frequently recovered facultative anaerobes in polymicrobial growth. Both aerobic and anaerobic data were available for 673/1094 samples, of which 68% represented a polymicrobial etiology and 32% as monomicrobial. Of the cases where complete clinical information was available (504/1094), the majority of the anaerobes were recovered from the skin and soft tissue infections (36.3%) and intra-abdominal infections (17.1%). The clinical specimen most frequently growing anaerobes was abscess (29.1%), followed by diabetic foot ulcers (14.1%).
CONCLUSIONS: The study documents the frequency of clinically significant anaerobic bacteria in various infections, and their associations with aerobes in polymicrobial growth. The present study may aid us in devising better therapeutic strategies against both aerobes and anaerobes in anaerobic infections, which is often empirical. Besides, the data can update clinicians with the changing patterns of anaerobic infections, which remains a neglected concern.

Myasthenia gravis (MG) is an acquired immune-mediated disorder of the neuromuscular junction that causes fluctuating skeletal muscle weakness and fatigue. Pediatric MG and adult MG have many different characteristics, and current MG diagnostic methods for children are not quite fit. Previous studies indicate that alterations in the gut microbiota may be associated with adult MG. However, it has not been determined whether the gut microbiota are altered in pediatric MG patients.
Our study recruited 53 pediatric MG patients and 46 age- and gender-matched healthy controls (HC). We sequenced the fecal samples of recruited individuals using whole-genome shotgun sequencing and analyzed the data with in-house bioinformatics pipeline.
We built an MG disease classifier based on the abundance of five species, Fusobacterium mortiferum, Prevotella stercorea, Prevotella copri, Megamonas funiformis, and Megamonas hypermegale. The classifier obtained 94% area under the curve (AUC) in cross-validation and 84% AUC in the independent validation cohort. Gut microbiome analysis revealed the presence of human adenovirus F/D in 10 MG patients. Significantly different pathways and gene families between MG patients and HC belonged to P. copri, Clostridium bartlettii, and Bacteroides massiliensis. Based on functional annotation, we found that the gut microbiome affects the production of short-chain fatty acids (SCFAs), and we confirmed the decrease in SCFA levels in pediatric MG patients via serum tests.
The study indicated that altered fecal microbiota might play vital roles in pediatric MG\'s pathogenesis by reducing SCFAs. The microbial markers might serve as novel diagnostic methods for pediatric MG.