Genomic, phenotypic, and clinical safety of Limosilactobacillus reuteri ATCC PTA 4659

Evaluating the safety of probiotic microorganisms is an important part of the development of probiotic products. In this study, we have performed a systematic safety assessment of Limosilactobacillus reuteri American Type Culture Collection (ATCC) PTA 4659 based on genome analysis, antibiotic susceptibility testing, phenotypic characterization, and a human clinical safety study. Genome sequence analysis showed that the strain is free from virulence and antibiotic resistance genes. Connected to this, phenotypic characterization showed that the strain is susceptible to the main classes of antibiotics. Limosilactobacillus reuteri ATCC PTA 4659 was shown to produce histamine, which has previously been described as an anti-inflammatory mediator produced by certain L. reuteri strains. However, the amount of histamine, a biogenic amine, poses no safety concern of a potential product. The strain was investigated in a human clinical safety study and was shown to survive passage through the gastrointestinal tract, both when administered at high [1 x 1011 colony-forming units (CFU)/day] and low doses (1 x 109 CFU/day). The clinical safety evaluation showed that the doses administered are safe for human consumption. Furthermore, carbohydrate utilization, mucus adhesion, and tolerance to acid and bile were studied. It was shown that L. reuteri ATCC PTA 4659 has a very high adhesion to mucus and tolerance to both gastric pH and bile, all potentially important properties for a probiotic strain. Altogether, this study has demonstrated that Limosilactobacillus reuteri ATCC PTA 4659 is safe for human consumption and along with its phenotypic characteristics and previously described anti-inflammatory effects, makes it a promising strain for future probiotic development. NCT01033539Graphical Abstract This is a systematic safety assessment of Limosilactobacillus reuteri ATCC PTA 4659 through genome analysis, phenotypic characterization, and a human clinical safety study

A mini-review: valuable allies for human health: probiotic strains of Limosilactobacillus reuteri

The World Health Organization defines probiotics as “live microorganisms which, when administered in adequate amounts, confer a health benefit on the host”. One of the most well studied probiotics is Limosilactobacillus reuteri, a Gram-positive, rod-shaped bacterium that colonizes the mucosal surfaces of mammals and birds and is considered autochthonous to the human microbiome. Genetic analyses have confirmed that this microorganism has co-evolved with its host, a prerequisite for the development of a mutualistic relation. On the one hand, L. reuteri contributes to the health of the host by releasing antimicrobial compounds, such as reuterin, and numerous active metabolites that can cross the epithelial barrier and reach different targets. Secondly, it can directly prevent the mucosal colonization by pathogenic bacteria helping in the prevention and restoration of dysbiosis due to the capability of forming biofilm. The characterization of numerous effector molecules produced by L. reuteri has provided a broad understanding of the mechanisms by which it not only displays antimicrobial and immunomodulatory activities within the gastrointestinal tract but can also influence the correct balance of distal locations of the body. This mini-review carries out a brief overview relating to the most well-known properties of L. reuteri highlighting the main biological processes involved

The Knee injury and Osteoarthritis Outcome Score (KOOS): from joint injury to osteoarthritis

The Knee injury and Osteoarthritis Outcome Score (KOOS) was developed as an extension of the WOMAC Osteoarthritis Index with the purpose of evaluating short-term and long-term symptoms and function in subjects with knee injury and osteoarthritis. The KOOS holds five separately scored subscales: Pain, other Symptoms, Function in daily living (ADL), Function in Sport and Recreation (Sport/Rec), and knee-related Quality of Life (QOL). The KOOS has been validated for several orthopaedic interventions such as anterior cruciate ligament reconstruction, meniscectomy and total knee replacement. In addition the instrument has been used to evaluate physical therapy, nutritional supplementation and glucosamine supplementation. The effect size is generally largest for the subscale QOL followed by the subscale Pain. The KOOS is a valid, reliable and responsive self-administered instrument that can be used for short-term and long-term follow-up of several types of knee injury including osteoarthritis. The measure is relatively new and further use of the instrument will add knowledge and suggest areas that need to be further explored and improved

Spontaneous emission noise resilience of coupled nanolasers

We investigate the spontaneous emission noise resilience of the phase-locked operation of two delay-coupled nanolasers. The system is modeled by semi-classical Maxwell–Bloch rate equations with stochastic Langevin-type noise sources. Our results reveal that a polarization dephasing time of two to three times the cavity photon lifetime maximizes the system’s ability to remain phase-locked in the presence of noise-induced perturbations. The Langevin noise term is caused by spontaneous emission processes which change both the intensity auto-correlation properties of the solitary lasers and the coupled system. In an experimental setup, these quantities are measurable and can be directly compared to our numerical data. The strong parameter dependence of the noise tolerance that we find may show possible routes for the design of robust on-chip integrated networks of nanolasers

The pan-genome of Lactobacillus reuteri strains originating from the pig gastrointestinal tract

Background Lactobacillus reuteri is a gut symbiont of a wide variety of vertebrate species that has diversified into distinct phylogenetic clades which are to a large degree host-specific. Previous work demonstrated host specificity in mice and begun to determine the mechanisms by which gut colonisation and host restriction is achieved. However, how L. reuteri strains colonise the gastrointestinal (GI) tract of pigs is unknown. Results To gain insight into the ecology of L. reuteri in the pig gut, the genome sequence of the porcine small intestinal isolate L. reuteri ATCC 53608 was completed and consisted of a chromosome of 1.94 Mbp and two plasmids of 138.5 kbp and 9.09 kbp, respectively. Furthermore, we generated draft genomes of four additional L. reuteri strains isolated from pig faeces or lower GI tract, lp167-67, pg-3b, 20-2 and 3c6, and subjected all five genomes to a comparative genomic analysis together with the previously completed genome of strain I5007. A phylogenetic analysis based on whole genomes showed that porcine L. reuteri strains fall into two distinct clades, as previously suggested by multi-locus sequence analysis. These six pig L. reuteri genomes contained a core set of 1364 orthologous gene clusters, as determined by OrthoMCL analysis, that contributed to a pan-genome totalling 3373 gene clusters. Genome comparisons of the six pig L. reuteri strains with 14 L. reuteri strains from other host origins gave a total pan-genome of 5225 gene clusters that included a core genome of 851 gene clusters but revealed that there were no pig-specific genes per se. However, genes specific for and conserved among strains of the two pig phylogenetic lineages were detected, some of which encoded cell surface proteins that could contribute to the diversification of the two lineages and their observed host specificity. Conclusions This study extends the phylogenetic analysis of L. reuteri strains at a genome-wide level, pointing to distinct evolutionary trajectories of porcine L. reuteri lineages, and providing new insights into the genomic events in L. reuteri that occurred during specialisation to their hosts. The occurrence of two distinct pig-derived clades may reflect differences in host genotype, environmental factors such as dietary components or to evolution from ancestral strains of human and rodent origin following contact with pig populations

Similar group mean scores, but large individual variations, in patient-relevant outcomes over 2 years in meniscectomized subjects with and without radiographic knee osteoarthritis.

Background Epidemiological studies have, so far, identified factors associated with increased risk for incident or progressive OA, such as age, sex, heredity, obesity, and joint injury. There is, however, a paucity of long-term data that provide information on the nature of disease progression on either group or individual levels. Such information is needed for identification of study cohorts and planning of clinical trials. The aim of the study was, thus, to assess the variation in pain and function on group and individual level over 2 years in previously meniscectomized individuals with and without radiographic knee osteoarthritis (OA). Methods 143 individuals (16% women, mean age at first assessment 50 years [range 27–83]) were assessed twice; approximately 14 and 16 years after isolated meniscectomy, with a median interval of 2.3 years (range 2.3–3.0). Radiographic OA (as assessed at the time of second evaluation) was present in the operated knee in 40%, and an additional 19% had a single osteophyte grade 1 in one or both of the tibiofemoral compartments. Subjects completed the self-administered and disease-specific Knee injury and Osteoarthritis Outcome Score (KOOS). Results There were no significant changes in the group mean KOOS subscale scores over the 2-year period. However, a great variability over time was seen within individual subjects. Out of 143 subjects, 16% improved and 12% deteriorated in the subscale Pain, and 13% improved and 14% deteriorated in the subscale ADL ≥ 10 points (the suggested threshold for minimal perceptible clinical change). Similar results were seen for remaining subscales. Conclusion Group mean scores for this study cohort enriched in incipient and early-stage knee OA were similar over 2 years, but pain, function and quality of life changed considerably in individuals. These results may be valid also for other at risk groups with knee OA, and motivate further careful examination of the natural history of OA, as well as properties of the OA outcome instruments used. Longitudinal outcome data in OA studies need to be analyzed both on an individual and a group level

Influence of adatom interactions on second layer nucleation

We develop a theory for the inclusion of adatom interactions in second layer nucleation occurring in epitaxial growth. The interactions considered are due to ring barriers between pairs of adatoms and binding energies of unstable clusters. The theory is based on a master equation, which describes the time development of microscopic states that are specified by cluster configurations on top of an island. The transition rates are derived by scaling arguments and tested against kinetic Monte-Carlo simulations. As an application we reanalyze experiments to determine the step edge barrier for Ag/Pt(111).Comment: 4 pages, 4 figure