Two cases of bacteremic pneumonia caused by Bifidobacterium species.

Clinical infections by Bifidobacterium species rarely developed. We report two cases of bacteremic pneumonia caused by B. pseudocatenulatum and B. dentium, respectively, in patients vulnerable to aspiration. These cases suggested the potential for cause of serious pneumonia caused by Bifidobacterium species, in patients with high risk of aspiration.

The Proportion of Bifidobacterium and Escherichia coli in Colon of Children with Recurrent Urinary Tract Infection.

Recurrent urinary tract infection (UTI) in children is a well-known risk factor of chronic kidney disease. Periurethral area is normally inhabited by non-pathogenic flora, such as Bifidobacterium sp., and pathogenic flora from gastrointestinal tract, such as Escherichia coli (E. coli), which can cause UTI. Dysbiosis between pathogenic and non-pathogenic bacteria leads to infections, but studies regarding dysbiosis and recurrent UTI have not yet been documented. To estimate the proportional differences between gastrointestinal E. coli and Bifidobacterium sp. in children with recurrent UTI, a cross-sectional study was conducted in children from age six months to <18 years old diagnosed with recurrent UTI in Dr. Cipto Mangunkusumo Hospital. Healthy children matched in gender and age were recruited as control group. Stool samples were obtained from all the children in the two groups. Stool DNA was extracted using real-time polymerized chain reaction method to count E. coli and Bifidobacterium sp. proportion. Children with recurrent UTI had significantly higher proportion of E. coli compared to control group (10.97 vs. 4.74; P = 0.014) and lower proportion of Bifidobacterium sp. (6.54 vs. 9.33; P = 0.594). In children with recurrent UTI group, E. coli proportion was found higher than Bifidobacterium sp. although not statistically significant (10.97 vs. 6.54; P = 0.819). In healthy controls, Bifidobacterium sp. proportion was significantly higher than E. coli (4.74 vs. 9.33; P = 0.021). The total amount of E. coli (996,004 vs. 1,099,271; P = 0.798) and Bifidobacterium sp. (835,921 vs. 1,196,991; P = 0.711) were higher in secondary UTI compared to the simple UTI. Proportion of E. coli is higher in children with recurrent UTI than in healthy children. The proportion of E. coli is higher than Bifidobacterium sp in the colon of children with recurrent UTI.

FN3 protein fragment containing two type III fibronectin domains from B. longum GT15 binds to human tumor necrosis factor alpha in vitro.

Most species of the genus Bifidobacterium contain the gene cluster PFNA, which is presumably involved in the species-specific communication between bacteria and their hosts. The gene cluster PFNA consists of five genes including fn3, which codes for a protein containing two fibronectin type III domains. Each fibronectin domain contains sites similar to cytokine-binding sites of human receptors. Based on this finding we assumed that this protein would bind specifically to human cytokines in vitro. We cloned a fragment of the fn3 gene (1503 bp; 501 aa) containing two fibronectin domains, from the strain B. longum subsp. longum GT15. After cloning the fragment into the expression vector pET16b and expressing it in E. coli, the protein product was purified to a homogenous state for further analysis. Using the immunoferment method, we tested the purified fragment's ability to bind the following human cytokines: IL-1ß, IL-6, IL-10, TNFα. We developed a sandwich ELISA system to detect any specific interactions between the purified protein and any of the studied cytokines. We found that the purified protein fragment only binds to TNFα.

Alloscardovia omnicolens emerging presence in premature rupture of membranes.

Alloscardovia omnicolens is a recently-reported microorganism with unknown pathogenic implications. It has been isolated in various clinical localizations but not in the endocervix. We isolated A. omnicolens in an endocervical sample from a 31-yr-old patient with preterm premature rupture of membranes (PPROM) in week 33+3 of pregnancy. The main risk of PPROM is prematurity and the possibility of developing infectious chorioamnionitis, which can be lethal for the mother and newborn. This is the first report of an association between A. omnicolens and PPROM, although its pathogenic role has not yet been elucidated.

Bifidobacterial Dialogue With Its Human Host and Consequent Modulation of the Immune System.

Since bifidobacteria are among the pioneering colonizers of the human infant gut, their interaction with their host is believed to start soon following birth. Several members of the Bifidobacterium genus are purported to exert various health-promoting effects at local and systemic levels, e.g., limiting pathogen colonization/invasion, influencing gut homeostasis, and influencing the immune system through changes in innate and/or adaptive immune responses. This has promoted extensive research efforts to shed light on the precise mechanisms by which bifidobacteria are able to stimulate and interact with the host immune system. These studies uncovered a variety of secreted or surface-associated molecules that act as essential mediators for the establishment of a bifidobacteria-host immune system dialogue, and that allow interactions with mucosa-associated immune cells. Additionally, the by-products generated from bifidobacterial carbohydrate metabolism act as vectors that directly and indirectly trigger the host immune response, the latter by stimulating growth of other commensal microorganisms such as propionate- or butyrate-producing bacteria. This review is aimed to provide a comprehensive overview on the wide variety of strategies employed by bifidobacteria to engage with the host immune system.

Neonatal oral fluid as a transmission route for bifidobacteria to the infant gut immediately after birth.

Bifidobacteria are one of the most abundant bacterial groups in the infant gut microbiota and are closely associated with infant health and can potentially affect health in later life. However, the details regarding the source of bifidobacteria have yet to be completely elucidated. This study aimed to assess neonatal oral fluid (OF) as a transmission route for bifidobacteria to the infant gut during delivery. Neonatal OF and infant feces (IF) were collected immediately and one month after birth from 15 healthy vaginally delivered newborns. Bifidobacterium strains were isolated from OF and IF samples, and the similarity of strains between the OF-IF pairs was evaluated based on the average nucleotide identity (ANI) value. The 16S rRNA gene sequencing results revealed the presence of Bifidobacteriaceae at >1% relative abundance in all OF samples. Bifidobacterium strains were isolated from OF (9/15) and IF (11/15) samples, and those sharing high genomic homology (ANI values >99.5%) between the neonatal OF and IF samples were present in one-third of the OF-IF pairs. The results of this study indicate that viable bifidobacteria are present in neonatal OF and that OF at birth is a possible transmission route of bifidobacteria to the infant gut.

Are probiotics safe? Bifidobacterium bacteremia in a child with severe heart failure.

Although few cases of bacteremia or sepsis caused by probiotics have been reported, it is important to consider their pathogenic potential, especially in some categories of patients. We report a case of Bifidobacterium spp bacteremia in a child with heart disease, undergoing probiotic supplementation to prevent antibiotic-associated diarrhea.

The Amount of Bifidobacterium Genus in Colorectal Carcinoma Tissue in Relation to Tumor Characteristics and Clinical Outcome.

Evidence indicates a complex link between microbiota, tumor characteristics, and host immunity in the tumor microenvironment. In experimental studies, bifidobacteria appear to modulate intestinal epithelial cell differentiation. Accumulating evidence suggests that bifidobacteria may enhance the antitumor immunity and efficacy of immunotherapy. We hypothesized that the amount of bifidobacteria in colorectal carcinoma tissue might be associated with tumor differentiation and higher immune response to colorectal cancer. Using a molecular pathologic epidemiology database of 1313 rectal and colon cancers, we measured the amount of Bifidobacterium DNA in carcinoma tissue by a quantitative PCR assay. The multivariable regression model was used to adjust for potential confounders, including microsatellite instability status, CpG island methylator phenotype, long-interspersed nucleotide element-1 methylation, and KRAS, BRAF, and PIK3CA mutations. Intratumor bifidobacteria were detected in 393 cases (30%). The amount of bifidobacteria was associated with the extent of signet ring cells (P = 0.002). Compared with Bifidobacterium-negative cases, multivariable odd ratios for the extent of signet ring cells were 1.29 (95% CI, 0.74-2.24) for Bifidobacterium-low cases and 1.87 (95% CI, 1.16-3.02) for Bifidobacterium-high cases (Ptrend = 0.01). The association between intratumor bifidobacteria and signet ring cells suggests a possible role of bifidobacteria in determining distinct tumor characteristics or as an indicator of dysfunctional mucosal barrier in colorectal cancer.

Sharing of human milk oligosaccharides degradants within bifidobacterial communities in faecal cultures supplemented with Bifidobacterium bifidum.

Gut microbiota of breast-fed infants are generally rich in bifidobacteria. Recent studies show that infant gut-associated bifidobacteria can assimilate human milk oligosaccharides (HMOs) specifically among the gut microbes. Nonetheless, little is known about how bifidobacterial-rich communities are shaped in the gut. Interestingly, HMOs assimilation ability is not related to the dominance of each species. Bifidobacterium longum susbp. longum and Bifidobacterium breve are commonly found as the dominant species in infant stools; however, they show limited HMOs assimilation ability in vitro. In contrast, avid in vitro HMOs consumers, Bifidobacterium bifidum and Bifidobacterium longum subsp. infantis, are less abundant in infant stools. In this study, we observed altruistic behaviour by B. bifidum when incubated in HMOs-containing faecal cultures. Four B. bifidum strains, all of which contained complete sets of HMO-degrading genes, commonly left HMOs degradants unconsumed during in vitro growth. These strains stimulated the growth of other Bifidobacterium species when added to faecal cultures supplemented with HMOs, thereby increasing the prevalence of bifidobacteria in faecal communities. Enhanced HMOs consumption by B. bifidum-supplemented cultures was also observed. We also determined the complete genome sequences of B. bifidum strains JCM7004 and TMC3115. Our results suggest B. bifidum-mediated cross-feeding of HMOs degradants within bifidobacterial communities.

Bifidobacterium scardovii aislado de 2 muestras consecutivas de orina / Bifidobacterium scardovii isolated from 2 consecutive urine samples

La especie Bifidobacterium scardovii está constituida por bacilos gram positivos anaerobios facultativos, cuyo desarrollo es estimulado por el CO2 y la anaerobiosis. Excepcionalmente se la ha asociado a infecciones humanas. Se presenta el caso de un paciente anoso con infección urinaria por B. scardovii y Enterococcus faecalis, ambos microorganismos aislados en 2 urocultivos consecutivos. El bacilo no desarrolló en los medios de cultivo habituales, pero sí en agar chocolate en CO2 y en agar Brucella suplementado, incubados durante 72 h a 35°C. La coloración de Gram alertó acerca de su presencia al observarse abundantes bacilos gram positivos irregulares con extremos bifurcados en forma de Y, y escasos cocos gram positivos. Es importante la coloración de Gram en orinas con piuria y la siembra en medios enriquecidos por tiempos prolongados. En este caso, sin el resultado del Gram y con el desarrollo de E. faecalis, no hubiésemos advertido la presencia del agente mayoritario.

Bifidobacterium scardovii species consists of facultative anaerobic gram-positive rods whose growth is stimulated by CO2 and anaerobiosis. Exceptionally it has been associated with infections in humans. An elderly male patient with a urinary tract infection due to B. scardovii and Enterococcus faecalis is presented here; both microorganisms were isolated from two consecutive urine samples. The bacillus did not grow on standard media, but on chocolate agar incubated in CO2 and on supplemented Brucella agar in an anaerobic atmosphere, incubated for 72 h at 35°C. Gram staining with abundant irregular gram-positive rods with Y-shaped ends and some gram-positive cocci alerted to its presence. The importance of the Gram stain test in urine samples with pyuria and the growth on enriched media for long periods is highlighted here. In this case, if we had not had the Gram stain test results, and had considered only the E. faecalis growth, we would have lost the major etiologic agent.

[Bifidobacterium scardovii isolated from 2 consecutive urine samples]. / Bifidobacterium scardovii aislado de 2 muestras consecutivas de orina.

Bifidobacterium scardovii species consists of facultative anaerobic gram-positive rods whose growth is stimulated by CO2 and anaerobiosis. Exceptionally it has been associated with infections in humans. An elderly male patient with a urinary tract infection due to B. scardovii and Enterococcus faecalis is presented here; both microorganisms were isolated from two consecutive urine samples. The bacillus did not grow on standard media, but on chocolate agar incubated in CO2 and on supplemented Brucella agar in an anaerobic atmosphere, incubated for 72h at 35°C. Gram staining with abundant irregular gram-positive rods with Y-shaped ends and some gram-positive cocci alerted to its presence. The importance of the Gram stain test in urine samples with pyuria and the growth on enriched media for long periods is highlighted here. In this case, if we had not had the Gram stain test results, and had considered only the E. faecalis growth, we would have lost the major etiologic agent.

A case of pyometrocolpos with Bifidobacterium species.

Bifidobacterium species, a normal commensal of the human gastrointestinal tract, female genitourinary tract and vagina is usually considered non-pathogenic and is being used therapeutically as probiotic due to its beneficial effects. However, there are several case reports implicating Bifidobacteria as the causative agent in various infectious conditions. Infections with Bifidobacteria are often ignored or underreported as they are part of the normal gut microbiome. Here we discuss a case of pyometrocolpos with Bifidobacterium species. Clinical outcome of the patient was good after emergency drainage and antibiotic treatment with Cefoperazone sulbactam and Metronidazole.

The Surface-Associated Exopolysaccharide of Bifidobacterium longum 35624 Plays an Essential Role in Dampening Host Proinflammatory Responses and Repressing Local TH17 Responses.

The immune-modulating properties of certain bifidobacterial strains, such as Bifidobacterium longum subsp. longum 35624 (B. longum 35624), have been well described, although the strain-specific molecular characteristics associated with such immune-regulatory activity are not well defined. It has previously been demonstrated that B. longum 35624 produces a cell surface exopolysaccharide (sEPS), and in this study, we investigated the role played by this exopolysaccharide in influencing the host immune response. B. longum 35624 induced relatively low levels of cytokine secretion from human dendritic cells, whereas an isogenic exopolysaccharide-negative mutant derivative (termed sEPSneg) induced vastly more cytokines, including interleukin-17 (IL-17), and this response was reversed when exopolysaccharide production was restored in sEPSneg by genetic complementation. Administration of B. longum 35624 to mice of the T cell transfer colitis model prevented disease symptoms, whereas sEPSneg did not protect against the development of colitis, with associated enhanced recruitment of IL-17+ lymphocytes to the gut. Moreover, intranasal administration of sEPSneg also resulted in enhanced recruitment of IL-17+ lymphocytes to the murine lung. These data demonstrate that the particular exopolysaccharide produced by B. longum 35624 plays an essential role in dampening proinflammatory host responses to the strain and that loss of exopolysaccharide production results in the induction of local TH17 responses. IMPORTANCE: Particular gut commensals, such as B. longum 35624, are known to contribute positively to the development of mucosal immune cells, resulting in protection from inflammatory diseases. However, the molecular basis and mechanisms for these commensal-host interactions are poorly described. In this report, an exopolysaccharide was shown to be decisive in influencing the immune response to the bacterium. We generated an isogenic mutant unable to produce exopolysaccharide and observed that this mutation caused a dramatic change in the response of human immune cells in vitro In addition, the use of mouse models confirmed that lack of exopolysaccharide production induces inflammatory responses to the bacterium. These results implicate the surface-associated exopolysaccharide of the B. longum 35624 cell envelope in the prevention of aberrant inflammatory responses.

Bifidobacteria-Insight into clinical outcomes and mechanisms of its probiotic action.

The invasion of pathogens causes a disruption of the gut homeostasis. Innate immune responses and those triggered by endogenous microbiota form the first line of defence in our body. Pathogens often successfully overcome the resistances offered, calling for therapeutic intervention. Conventional strategy involving antibiotics might eradicate pathogens, but often leave the gut uncolonised and susceptible to recurrences. Probiotic supplements are useful alternatives. Bifidobacterium is one of widely studied probiotic genus, effective in restoring gut homeostasis. Mechanisms of probiotic action of bifidobacteria are several, often with strain-specificity. Analysis of streamlined literature reports reveal that although most studies report the probiotic aspect of bifidobacteria, sporadic documented contradictory results exist, challenging its therapeutic application and prompting studies to unambiguously establish the strain-associated probiotic activity and negate adverse effects prior to its clinical administration. Multi-strain/combinatorial therapy possibly relies on a combination of underlying operating mechanisms, each contributing towards enhanced probiotic efficacy, understanding which could help in developing customised formulations against targeted pathogens. Bifidogenic activity is also mediated by surface-associated structural components such as exopolysaccharides, lipoteichoic acids along with metabolites and bifidocins. This highlights scope for developing advanced structural therapeutic strategy which might be pivotal in replacing intact cell probiotics therapy.

Bifidobacterium longum bacteremia in preterm infants receiving probiotics.

Administration of probiotics to premature newborns has been shown to prevent necrotizing enterocolitis and reduce all-cause mortality. In our hospital, we documented 2 cases of Bifidobacterium longum subspecies infantis bacteremia in newborns receiving probiotics. By comparative genomics, we confirmed that the strains isolated from each patient originated from the probiotics.

Bifidobacterium--friend or foe? A case of urinary tract infection with Bifidobacterium species.

Bifidobacterium-a commensal of the human intestine is considered non-pathogenic and has been advocated as a probiotic due to its potential beneficial effects. However, there have been case reports implicating bifidobacteria as pathogenic agents in a variety of different infectious conditions. We discuss here one such case of a complicated urinary tract infection associated with Bifidobacterium spp.

Genomic characterization and transcriptional studies of the starch-utilizing strain Bifidobacterium adolescentis 22L.

Bifidobacteria are members of the gut microbiota, but the genetic basis for their adaptation to the human gut is poorly understood. The analysis of the 2,203,222-bp genome of Bifidobacterium adolescentis 22L revealed a nutrient acquisition strategy that targets diet/plant-derived glycans, in particular starch and starch-like carbohydrates. Starch-like carbohydrates were shown to support the growth of B. adolescentis 22L. Transcriptome profiling of 22L cultures grown under in vitro conditions or during colonization of the murine gut by RNA sequencing and quantitative real-time PCR assays revealed the expression of a set of chromosomal loci responsible for starch metabolism as well as for pilus production. Such extracellular structures include so-called sortase-dependent and type IVb pili, which may be involved in gut colonization of 22L through adhesion to extracellular matrix proteins.

The relationship between bifidobacteria and allergic asthma and/or allergic dermatitis: a prospective study of 0-3 years-old children in Turkey.

Bifidobacteria are beneficial bacteria for humans. These bacteria are particularly effective at protecting against infectious diseases and modulating the immune response. It was shown that in newborns, the fecal distribution of the colonizing Bifidobacterium species influences the prevalence of allergic diseases. This study aimed to compare the faecal Bifidobacterium species of allergic children to those of healthy children to detect species level differences in faecal distribution. Stool samples were obtained from 99 children between 0 and 3 years of age whose clinical symptoms and laboratory reports were compatible with atopic dermatitis and allergic asthma. Samples were also obtained from 102 healthy children who were similar to the case group with respect to age and sex. Bifidobacteria were isolated by culture and identified at the genus level by API 20 A. In addition, 7 unique species-specific primers were used for the molecular characterization of bifidobacteria. The McNemar test was used for statistical analyses, and p < 0.05 was accepted as significant. Bifidobacterium longum was detected in 11 (11.1%) of the allergic children and in 31 (30.3%) of the healthy children. Statistical analysis revealed a significant difference in the prevalence of B. longum between these two groups (X(2): 11.2, p < 0.001). However, no significant differences in the prevalence of other Bifidobacterium species were found between faecal samples from healthy and allergic children. (p > 0.05). The significant difference in the isolation of B. longum from our study groups suggests that this species favors the host by preventing the development of asthma and allergic dermatitis. Based on these results, we propose that the production of probiotics in accordance with country-specific Bifidobacterium species densities would improve public health. Thus, country-specific prospective case-control studies that collect broad data sets are needed.