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The intestinal microbiota are a complex ecosystem influencing the immunoregulation of the human host, providing protection from colonising pathogens and producing SCFA as the main energy source of colonocytes. Our objective was to investigate the effect of dietary fibre exclusion and supplementation on the intestinal microbiota and SCFA concentrations. Faecal samples were obtained from healthy volunteers before and after two 14 d periods of consuming formulated diets devoid or supplemented with fibre (14 g/l). The faecal microbiota were analysed using fluorescent in situ hybridisation and SCFA were measured using GLC. There were large and statistically significant reductions in the numbers of the Faecalibacterium prausnitzii (P ≤ 0·01) and Roseburia spp. (P ≤ 0·01) groups during both the fibre-free and fibre-supplemented diets. Significant and strong positive correlations between the proportion of F. prausnitzii and the proportion of butyrate during both baseline normal diets were found (pre-fibre free r 0·881, P = 0·001; pre-fibre supplemented r 0·844, P = 0·002). A significant correlation was also found between the proportional reduction in F. prausnitzii and the proportional reduction in faecal butyrate during both the fibre-free (r 0·806; P = 0·005) and the fibre-supplemented diet (r 0·749; P = 0·013). These findings may contribute to the understanding of the association between fibre, microbiota and fermentation in health, during enteral nutrition and in disease states such as Crohn's disease.

Quaternary ammonium methacryloxy silicate (QAMS)-containing acrylic resin demonstrated contact-killing antimicrobial ability in vitro after three months of water storage. The objective of the present double-blind randomised clinical trial was to determine the in vivo antimicrobial efficacy of QAMS-containing orthodontic acrylic by using custom-made removable retainers that were worn intraorally by 32 human subjects to create 48-hour multi-species plaque biofilms, using a split-mouth study design. Two control QAMS-free acrylic disks were inserted into the wells on one side of an orthodontic retainer, and two experimental QAMS-containing acrylic disks were inserted into the wells on the other side of the same retainer. After 48 hours, the disks were retrieved and examined for microbial vitality using confocal laser scanning microscopy. No harm to the oral mucosa or systemic health occurred. In the absence of carry-across effect and allocation bias (disks inserted in the left or right side of retainer), significant difference was identified between the percentage kill in the biovolume of QAMS-free control disks (3.73 ± 2.11%) and QAMS-containing experimental disks (33.94 ± 23.88%) retrieved from the subjects (P ≤ 0.001). The results validated that the QAMS-containing acrylic exhibits favourable antimicrobial activity against plaque biofilms in vivo . The QAMS-containing acrylic may also be used for fabricating removable acrylic dentures.

Fusobacterium nucleatum is an oral anaerobe recently found to be prevalent in human colorectal cancer (CRC) where it is associated with poor treatment outcome. In mice, hematogenous F. nucleatum can colonize CRC tissue using its lectin Fap2, which attaches to tumor-displayed Gal-GalNAc. Here, we show that Gal-GalNAc levels increase as human breast cancer progresses, and that occurrence of F. nucleatum gDNA in breast cancer samples correlates with high Gal-GalNAc levels. We demonstrate Fap2-dependent binding of the bacterium to breast cancer samples, which is inhibited by GalNAc. Intravascularly inoculated Fap2-expressing F. nucleatum ATCC 23726 specifically colonize mice mammary tumors, whereas Fap2-deficient bacteria are impaired in tumor colonization. Inoculation with F. nucleatum suppresses accumulation of tumor infiltrating T cells and promotes tumor growth and metastatic progression, the latter two of which can be counteracted by antibiotic treatment. Thus, targeting F. nucleatum or Fap2 might be beneficial during treatment of breast cancer. High levels of Fusobacterium nucleatum have been associated with poor overall survival in patients with colorectal and esophageal cancer. Here, the authors show that F. nucleatum is abundant in breast cancer samples and that the colonization by F. nucleatum accelerates tumor growth and metastasis in preclinical breast cancer models.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the pandemic Coronavirus Disease 2019 (COVID-19). This virus is highly transmissible among individuals through both droplets and aerosol leading to determine severe pneumonia. Among the various factors that can influence both the onset of disease and the severity of its complications, the microbiome composition has also been investigated. Recent evidence showed the possible relationship between gut, lung, nasopharyngeal, or oral microbiome and COVID-19, but very little is known about it. Therefore, we aimed to verify the relationships between nasopharyngeal microbiome and the development of either COVID-19 or the severity of symptoms. To this purpose, we analyzed, by next generation sequencing, the hypervariable V1-V2-V3 regions of the bacterial 16S rRNA in nasopharyngeal swabs from SARS-CoV-2 infected patients (n=18) and control (CO) individuals (n=12) using Microbiota solution A (Arrow Diagnostics). We found a significant lower abundance of Proteobacteria and Fusobacteria in COVID-19 patients in respect to CO (p=0.003 and p<0.0001, respectively) from the phylum up to the genus (p<0.001). The Fusobacterium periodonticum ( FP ) resulted as the most significantly reduced species in COVID-19 patients respect to CO. FP is reported as being able to perform the surface sialylation. Noteworthy, some sialic acids residues on the cell surface could work as additional S protein of SARS-CoV-2 receptors. Consequently, SARS-CoV-2 could use sialic acids as receptors to bind to the epithelium of the respiratory tract, promoting its clustering and the disease development. We can therefore speculate that the significant reduction of FP in COVID-19 patients could be directly or indirectly linked to the modulation of sialic acid metabolism. Finally, viral or environmental factors capable of interfering with sialic metabolism could determine a fall in the individual protection from SARS-CoV-2. Further studies are necessary to clarify the precise role of FP in COVID-19.

Background Esophageal squamous cell carcinoma (ESCC) is the major type of esophageal cancer in China. The role of the bacteria present in ESCC tissue in neoplastic progression has not been fully elucidated. This study aimed to uncover different bacterial communities in ESCC tissues and examine the correlation between the abundance of the esophageal flora and clinicopathologic characteristics of ESCC. Results Microorganisms in tumors and normal tissues showed obvious clustering characteristics. The abundance of Fusobacterium ( P  = 0.0052) was increased in tumor tissues. The high level of Fusobacterium nucleatum was significantly associated with pT stage ( P  = 0.039) and clinical stage ( P  = 0.0039). The WES data showed that COL22A1, TRBV10–1, CSMD3, SCN7A and PSG11 were present in only the F. nucleatum -positive ESCC samples. GO and protein domain enrichment results suggested that epidermal growth factor might be involved in the regulation of cell apoptosis in F. nucleatum -positive ESCC. Both a higher mutational burden and F. nucleatum -positive was observed in tumors with metastasis than in tumors without metastasis. Conclusion F. nucleatum is closely related to the pT stage and clinical stage of ESCC. The abundance of F. nucleatum and tumor mutation burden may be used in combination as a potential method to predict metastasis in ESCC.

The faecal microbiota plays a critical role in host health, with alterations in the human faecal microbial composition associated with various conditions, particularly diarrhoeal diseases. However, little is known about microbial changes during cryptosporidiosis, one of the most important diarrhoeal diseases caused by protozoa in cattle. In this study, alterations in the faecal microbiota of neonatal calves as a result of Cryptosporidium parvum infection were investigated on a C. parvum -positive farm. Comparisons were made among groups of C. parvum- infected, rotavirus-infected, and the pathogen-negative calves. A specific increase in the abundance of Fusobacterium was observed in the faecal microbiota of C. parvum -infected animals. Diarrhoea severity increased in accordance with the abundance of C. parvum and Fusobacterium . Moreover, the specific increase of Fusobacterium appeared to be a universal feature of C. parvum infection, since neonatal calves from geographically separated areas showed the same result. These observations indicated that the growth of Fusobacterium may be an important aggravating factor of cryptosporidiosis.

Background The human gut harbors a diverse microbiota that is crucial for maintaining health but also contributes to several diseases. Understanding how microbial communities are assembled and maintained is critical for advancing gut health. Results We identified a unique interaction between the pathobiont Fusobacterium varium and the symbiont Faecalibacterium prausnitzii , both members of the gut microbial community; their interaction is driven by metabolites and direct cell-to-cell contact. Growth of F. varium was inhibited in the presence of F. prausnitzii because of a decrease in pH and an increase in β -hydroxybutyric acid. Conversely, the growth of F. prausnitzii was promoted in the presence of F. varium , likely via direct contact. Conclusions These findings highlight the importance of metabolite-driven interactions and direct contact in shaping gut microbial communities and emphasize the potential of interactions between F. prausnitzii and F. varium in influencing gut health. FLryDwzSyUiUebEJdxwjmw Video Abstract

The microbiota in the human gut is strongly correlated with the progression of colorectal cancer (CRC) and with therapeutic responses to CRC. Here, by leveraging the higher concentration of the pro-tumoural Fusobacterium nucleatum and the absence of antineoplastic butyrate-producing bacteria in the faecal microbiota of patients with CRC, we show that—in mice with orthotopic colorectal tumours or with spontaneously formed colorectal tumours—oral or intravenous administration of irinotecan-loaded dextran nanoparticles covalently linked to azide-modified phages that inhibit the growth of F. nucleatum significantly augments the efficiency of first-line chemotherapy treatments of CRC. We also show that oral administration of the phage-guided irinotecan-loaded nanoparticles in piglets led to negligible changes in haemocyte counts, immunoglobulin and histamine levels, and liver and renal functions. Phage-guided nanotechnology for the modulation of the gut microbiota might inspire new approaches for the treatment of CRC. Dextran nanoparticles loaded with a chemotherapeutic agent and bound to phages that eliminate a pro-tumoural gut bacterium and promote the growth of anticancer-compound-producing bacteria boost chemotherapy responses in mouse models of colorectal cancer.

Background Previous research has shown the oxidizing properties and microbiological efficacies of chlorine dioxide (ClO 2 ). Its clinical efficacies on oral malodor have been evaluated and reported only in short duration trials, moreover, no clinical studies have investigated its microbiological efficacies on periodontal and malodorous bacteria. Thus, the aim of this study was to assess the inhibitory effects of a mouthwash containing ClO 2 used for 7 days on morning oral malodor and on salivary periodontal and malodorous bacteria. Methods/Design A randomized, double blind, crossover, placebo-controlled trial was conducted among 15 healthy male volunteers, who were divided into 2 groups. Subjects were instructed to rinse with the experimental mouthwash containing ClO 2 or the placebo mouthwash, without ClO 2 , twice per day for 7 days. After a one week washout period, each group then used the opposite mouthwash for 7 days. At baseline and after 7 days, oral malodor was evaluated with Organoleptic measurement (OM), and analyzed the concentrations of hydrogen sulfide (H 2 S), methyl mercaptan (CH 3 SH) and dimethyl sulfide ((CH 3 ) 2 S), the main VSCs of human oral malodor, were assessed by gas chromatography (GC). Clinical outcome variables included plaque and gingival indices, and tongue coating index. The samples of saliva were microbiologically investigated. Quantitative and qualitative analyses were performed using the polymerase chain reaction-Invader method. Results and Discussion The baseline oral condition in healthy subjects in the 2 groups did not differ significantly. After rinsing with the mouthwash containing ClO 2 for 7 days, morning bad breath decreased as measured by the OM and reduced the concentrations of H 2 S, CH 3 SH and (CH 3 ) 2 S measured by GC, were found. Moreover ClO 2 mouthwash used over a 7-day period appeared effective in reducing plaque, tongue coating accumulation and the counts of Fusobacterium nucleatum in saliva. Future research is needed to examine long-term effects, as well as effects on periodontal diseases and plaque accumulation in a well-defined sample of halitosis patients and broader population samples. Trial registration ClinicalTrials.gov NCT00748943

Colorectal cancer (CRC) is a leading cause of cancer‐related mortality, with Fusobacterium nucleatum (F. nucleatum) identified as a key contributor to its progression. This study explores a novel therapy that targets this pathogen by using a bioengineered probiotic that expresses guided antimicrobial peptides (gAMPs) to selectively inhibit F. nucleatum. Lactococcus lactis MG1363 was engineered to express gAMPs derived from Ovispirin and Cathelin‐related peptide SCF, linked to a Statherin‐derived guide peptide that binds specifically to the F. nucleatum membrane porin FomA. The bacteria expressed the AMP/gAMP under the induction of the PNisA promoter by nisin and secreted it via the extracellular secretion signal usp45. The resultant synthetic peptides and probiotics were assayed for antimicrobial activity against the targeted F. nucleatum and other non‐target bacteria. Biofilm inhibition and growth kinetic assays were performed with synthetic peptides in vitro or the probiotic in co‐culture with a polymicrobial community. Statherin‐derived guide peptide enhanced the binding affinity to F. nucleatum, significantly increasing attachment compared to control peptides. In vitro assays revealed that both unguided and guided AMPs effectively inhibited biofilm formation in F. nucleatum, with gAMPs showing reduced toxicity against non‐target bacteria. The gAMPs were more effective in modulating growth kinetics, exhibiting selective toxicity towards F. nucleatum at lower concentrations. Co‐culture experiments in a simulated human gut microbiome showed the gAMP probiotic maintained microbial diversity while effectively reducing F. nucleatum abundance. Quantitative PCR and 16S rRNA sequencing confirmed that gAMP treatment preserved the richness of the microbiota, contrasting with significant dysbiosis observed in control samples. These findings support the potential of engineered probiotics as a therapeutic approach that targets CRC‐associated F. nucleatum. We engineered a probiotic using Lactococcus lactis that targets Fusobacterium nucleatum, a cancer‐associated microbe, by secreting guided antimicrobial peptides (gAMPs) binding to the FomA porin protein. This approach inhibits biofilms, preserves microbial diversity and provides a precise, microbiome‐sparing alternative to broad‐spectrum antibiotics for treating infections.