Vaginal epithelial cells regulate membrane adhesiveness to co-ordinate bacterial adhesion.

Vaginal epithelium is colonized by different bacterial strains and species. The bacterial composition of vaginal biofilms controls the balance between health and disease. Little is known about the relative contribution of the epithelial and bacterial cell surfaces to bacterial adhesion and whether and how adhesion is regulated over cell membrane regions. Here, we show that bacterial adhesion forces with cell membrane regions not located above the nucleus are stronger than with regions above the nucleus both for vaginal pathogens and different commensal and probiotic lactobacillus strains involved in health. Importantly, adhesion force ratios over membrane regions away from and above the nucleus coincided with the ratios between numbers of adhering bacteria over both regions. Bacterial adhesion forces were dramatically decreased by depleting the epithelial cell membrane of cholesterol or sub-membrane cortical actin. Thus, epithelial cells can regulate membrane regions to which bacterial adhesion is discouraged, possibly to protect the nucleus.

Efficacy of Using Probiotics with Antagonistic Activity against Pathogens of Wound Infections: An Integrative Review of Literature.

The skin and its microbiota serve as physical barriers to prevent invasion of pathogens. Skin damage can be a consequence of illness, surgery, and burns. The most effective wound management strategy is to prevent infections, promote healing, and prevent excess scarring. It is well established that probiotics can aid in skin healing by stimulating the production of immune cells, and they also exhibit antagonistic effects against pathogens via competitive exclusion of pathogens. Our aim was to conduct a review of recent literature on the efficacy of using probiotics against pathogens that cause wound infections. In this integrative review, we searched through the literature published in the international following databases: PubMed, ScienceDirect, Web of Science, and Scopus using the search terms "probiotic" AND "wound infection." During a comprehensive review and critique of the selected research, fourteen in vitro studies, 8 animal studies, and 19 clinical studies were found. Two of these in vitro studies also included animal studies, yielding a total of 39 articles for inclusion in the review. The most commonly used probiotics for all studies were well-known strains of the species Lactobacillus plantarum, Lactobacillus casei, Lactobacillus acidophilus, and Lactobacillus rhamnosus. All in vitro studies showed successful inhibition of chosen skin or wound pathogens by the selected probiotics. Within the animal studies on mice, rats, and rabbits, probiotics showed strong opportunities for counteracting wound infections. Most clinical studies showed slight or statistically significant lower incidence of surgical site infections, foot ulcer infection, or burn infections for patients using probiotics. Several of these studies also indicated a statistically significant wound healing effect for the probiotic groups. This review indicates that exogenous and oral application of probiotics has shown reduction in wound infections, especially when used as an adjuvant to antibiotic therapy, and therefore the potential use of probiotics in this field remains worthy of further studies, perhaps focused more on typical skin inhabitants as next-generation probiotics with high potential.

Pre-, pro- and synbiotics in cancer prevention and treatment-a review of basic and clinical research.

There is a growing appreciation of the role of the human microbiota in the pathophysiology of cancer. Pre-, pro- and synbiotics are some of the best evidenced means of manipulating the microbiota for therapeutic benefit and their potential role in the prevention and treatment of cancer has garnered significant interest. In this review, we discuss how these agents may have oncosuppressive effects by maintaining intestinal barrier function, immunomodulation, metabolism and preventing host cell proliferation. We highlight the epidemiological and trials-based evidence supporting a role for pre-, pro- and synbiotics in the prevention of cancer. Ultimately, there is more evidence in support of these agents as adjuncts in the treatment of cancer. We discuss their roles in optimising the efficacy and/or minimising the adverse effects of chemotherapy and radiotherapy, antibiotics and surgery. Although we see significant promise in the application of pre-, pro- and synbiotics for clinical benefit in oncology patients, the field is very much in its infancy and oncologists face substantial challenges in advising their patients appropriately.

Perspective: Fundamental Limitations of the Randomized Controlled Trial Method in Nutritional Research: The Example of Probiotics.

Studies on the relation between health and nutrition are often inconclusive. There are concerns about the validity of many research findings, and methods that can deliver high-quality evidence-such as the randomized controlled trial (RCT) method-have been embraced by nutritional researchers. Unfortunately, many nutritional RCTs also yield ambiguous results. It has been argued that RCTs are ill-suited for certain settings, including nutritional research. In this perspective, we investigate whether there are fundamental limitations of the RCT method in nutritional research. To this end, and to limit the scope, we use probiotic studies as an example. We use an epistemological approach and evaluate the presuppositions that underlie the RCT method. Three general presuppositions are identified and discussed. We evaluate whether these presuppositions can be considered true in probiotic RCTs, which appears not always to be the case. This perspective concludes by exploring several alternative study methods that may be considered for future probiotic or nutritional intervention trials.

Women and Their Microbes: The Unexpected Friendship.

Communities of microbiota have been associated with numerous health outcomes, and while much emphasis has been placed on the gastrointestinal niche, there is growing interest in the microbiome specific for female reproductive health and the health of their offspring. The vaginal microbiome plays an essential role not only in health and dysbiosis, but also potentially in successful fertilization and healthy pregnancies. In addition, microbial communities have been isolated from formerly forbidden sterile niches such as the placenta, breast, uterus, and Fallopian tubes, strongly suggesting an additional microbial role in women's health. A combination of maternally linked prenatal, birth, and postnatal factors, together with environmental and medical interventions, influence early and later life through the microbiome. Here, we review the role of microbes in female health focusing on the vaginal tract and discuss how male and female reproductive microbiomes are intertwined with conception and how mother-child microbial transfer is a key determinant in infant health, and thus the next generation.

Lactobacilli require physical contact to reduce staphylococcal TSST-1 secretion and vaginal epithelial inflammatory response.

ITALIC! Staphylococcus aureusbiofilms can be found on vaginal epithelia, secreting toxins and causing inflammation. The co-vaginal species ITALIC! Lactobacilluscan alter staphylococcal-induced epithelial secretion of inflammatory cytokines and quench staphylococcal toxic shock syndrome toxin-1 secretion. It is hypothesized that these effects of lactobacilli require direct physical contact between lactobacilli, staphylococci and the epithelium. Indeed, lactobacilli only reduced ITALIC! S. aureus-induced inflammatory cytokine expression when allowed physical contact with vaginal epithelial cells. Furthermore, a reduction in toxic shock syndrome toxin-1 secretion only occurred when a probiotic ITALIC! Lactobacillusstrain was allowed contact, but not when being physically separated from ITALIC! S. aureus Bacterial-probe atomic force microscopy demonstrated that lactobacilli and staphylococci strongly adhere to epithelial cells, while lactobacilli adhere stronger to staphylococci than staphylococci to each other, giving lactobacilli opportunity to penetrate and reside in staphylococcal biofilms, as visualized using confocal laser scanning microscopy with fluorescence ITALIC! in situhybridization probes. These results identify that physical contact and biochemical signaling by lactobacilli are intrinsically linked mechanisms that reduce virulence of ITALIC! S. aureusbiofilm.

Adhesion forces and coaggregation between vaginal staphylococci and lactobacilli.

Urogenital infections are the most common ailments afflicting women. They are treated with dated antimicrobials whose efficacy is diminishing. The process of infection involves pathogen adhesion and displacement of indigenous Lactobacillus crispatus and Lactobacillus jensenii. An alternative therapeutic approach to antimicrobial therapy is to reestablish lactobacilli in this microbiome through probiotic administration. We hypothesized that lactobacilli displaying strong adhesion forces with pathogens would facilitate coaggregation between the two strains, ultimately explaining the elimination of pathogens seen in vivo. Using atomic force microscopy, we found that adhesion forces between lactobacilli and three virulent toxic shock syndrome toxin 1-producing Staphylococcus aureus strains, were significantly stronger (2.2-6.4 nN) than between staphylococcal pairs (2.2-3.4 nN), especially for the probiotic Lactobacillus reuteri RC-14 (4.0-6.4 nN) after 120 s of bond-strengthening. Moreover, stronger adhesion forces resulted in significantly larger coaggregates. Adhesion between the bacteria occurred instantly upon contact and matured within one to two minutes, demonstrating the potential for rapid anti-pathogen effects using a probiotic. Coaggregation is one of the recognized mechanisms through which lactobacilli can exert their probiotic effects to create a hostile micro-environment around a pathogen. With antimicrobial options fading, it therewith becomes increasingly important to identify lactobacilli that bind strongly with pathogens.

Microbiota restoration: natural and supplemented recovery of human microbial communities.

In a healthy host, a balance exists between members of the microbiota, such that potential pathogenic and non-pathogenic organisms can be found in apparent harmony. During infection, this balance can become disturbed, leading to often dramatic changes in the composition of the microbiota. For most bacterial infections, nonspecific antibiotics are used, killing the non-pathogenic members of the microbiota as well as the pathogens and leading to a substantial delay in the restoration of a healthy microbiota. However, in some cases, infections can self-resolve without the intervention of antibiotics. In this Review, we explore the mechanisms underlying microbiota restoration following insult (antibiotic or otherwise) to the skin, oral cavity, and gastrointestinal and urogenital tracts, highlighting recovery by natural processes and after probiotic administration.