The Influence of Different Physical Activity Behaviours on the Gut Microbiota of Older Irish Adults.

OBJECTIVE: A 24-hour day is made up of time spent in a range of physical activity (PA) behaviours, including sleep, sedentary time, standing, light-intensity PA (LIPA) and moderate-to-vigorous PA (MVPA), all of which may have the potential to alter an individual's health through various different pathways and mechanisms. This study aimed to explore the relationship between PA behaviours and the gut microbiome in older adults. DESIGN: Cross-sectional study. SETTINGS AND PARTICIPANTS: Participants (n=100; age 69.0 [3.0] years; 44% female) from the Mitchelstown Cohort Rescreen (MCR) Study (2015-2017). METHODS: Participants provided measures of gut microbiome composition (profiled by sequencing 16S rRNA gene amplicons), and objective measures of PA behaviours (by a 7-day wear protocol using an activPAL3 Micro). RESULTS: Standing time was positively correlated with the abundance of butyrate-producing and anti-inflammatory bacteria, including Ruminococcaceae, Lachnospiraceae and Bifidobacterium, MVPA was positively associated with the abundance of Lachnospiraceae bacteria, while sedentary time was associated with lower abundance of Ruminococcaceae and higher abundance of Streptococcus spp. CONCLUSION: Physical activity behaviours appear to influence gut microbiota composition in older adults, with different PA behaviours having diverging effects on gut microbiota composition.

Potentially modifiable determinants of malnutrition in older adults: A systematic review.

BACKGROUND & AIMS: Malnutrition in older adults results in significant personal, social, and economic burden. To combat this complex, multifactorial issue, evidence-based knowledge is needed on the modifiable determinants of malnutrition. Systematic reviews of prospective studies are lacking in this area; therefore, the aim of this systematic review was to investigate the modifiable determinants of malnutrition in older adults. METHODS: A systematic approach was taken to conduct this review. Eight databases were searched. Prospective cohort studies with participants of a mean age of 65 years or over were included. Studies were required to measure at least one determinant at baseline and malnutrition as outcome at follow-up. Study quality was assessed using a modified version of the Quality in Prognosis Studies (QUIPS) tool. Pooling of data in a meta-analysis was not possible therefore the findings of each study were synthesized narratively. A descriptive synthesis of studies was used to present results due the heterogeneity of population source and setting, definitions of determinants and outcomes. Consistency of findings was assessed using the schema: strong evidence, moderate evidence, low evidence, and conflicting evidence. RESULTS: Twenty-three studies were included in the final review. Thirty potentially modifiable determinants across seven domains (oral, psychosocial, medication and care, health, physical function, lifestyle, eating) were included. The majority of studies had a high risk of bias and were of a low quality. There is moderate evidence that hospitalisation, eating dependency, poor self-perceived health, poor physical function and poor appetite are determinants of malnutrition. Moderate evidence suggests that chewing difficulties, mouth pain, gum issues co-morbidity, visual and hearing impairments, smoking status, alcohol consumption and physical activity levels, complaints about taste of food and specific nutrient intake are not determinants of malnutrition. There is low evidence that loss of interest in life, access to meals and wheels, and modified texture diets are determinants of malnutrition. Furthermore, there is low evidence that psychological distress, anxiety, loneliness, access to transport and wellbeing, hunger and thirst are not determinants of malnutrition. There appears to be conflicting evidence that dental status, swallowing, cognitive function, depression, residential status, medication intake and/or polypharmacy, constipation, periodontal disease are determinants of malnutrition. CONCLUSION: There are multiple potentially modifiable determinants of malnutrition however strong robust evidence is lacking for the majority of determinants. Better prospective cohort studies are required. With an increasingly ageing population, targeting modifiable factors will be crucial to the effective treatment and prevention of malnutrition.

Compositional dynamics of the human intestinal microbiota with aging: implications for health.

The human gut contains trillions of microbes which form an essential part of the complex ecosystem of the host. This microbiota is relatively stable throughout adult life, but may fluctuate over time with aging and disease. The gut microbiota serves a number of functions including roles in energy provision, nutrition and also in the maintenance of host health such as protection against pathogens. This review summarizes the age-related changes in the microbiota of the gastrointestinal tract (GIT) and the link between the gut microbiota in health and disease. Understanding the composition and function of the gut microbiota along with the changes it undergoes overtime should aid the design of novel therapeutic strategies to counteract such alterations. These strategies include probiotic and prebiotic preparations as well as targeted nutrients, designed to enrich the gut microbiota of the aging population.

Failure of surface ring mutant strains of Helicobacter mustelae to persistently infect the ferret stomach.

Helicobacter mustelae, the gastric pathogen of ferrets, produces an array of surface ring structures which have not been described for any other member of the genus Helicobacter, including H. pylori. The unique ring structures are composed of a protein named Hsr. To investigate whether the Hsr rings are important for colonization of the ferret stomach, ferrets specific pathogen free for H. mustelae were inoculated with an Hsr-deficient mutant strain or the wild-type H. mustelae strain. Quantitative cultures from antral biopsy specimens obtained at 3, 6, and 9 weeks postinoculation demonstrated no significant difference in the levels of bacteria in the ferrets that received the Hsr-negative strain and the ferrets infected with the parent strain. However, when the ferrets were biopsied at 12 and 15 weeks and necropsied at 18 weeks after infection, the levels of bacteria of the Hsr-negative strain in the stomach antrum were significantly reduced. This decline contrasted the robust antral colonization by the wild-type strain. The Hsr-negative strain did not efficiently colonize the gastric body of the study ferrets. Histological examination at 18 weeks postinoculation revealed minimal gastric inflammation in the animals that received the mutant H. mustelae strain, a finding consistent with its waning infection status, whereas lesions characteristic of helicobacter infection were present in ferrets infected with the wild-type strain. Scant colonization by the Hsr-negative H. mustelae strain at the end of the 18-week study, despite initial successful colonization, indicates an inability of the mutant to persist, perhaps due to a specific host response.

Molecular characterization of a flagellar export locus of Helicobacter pylori.

Motility of Helicobacter species has been shown to be essential for successful colonization of the host. We have investigated the organization of a flagellar export locus in Helicobacter pylori. A 7-kb fragment of the H. pylori CCUG 17874 genome was cloned and sequenced, revealing an operon comprising an open reading frame of unknown function (ORF03), essential housekeeping genes (ileS and murB), flagellar export genes (fliI and fliQ), and a homolog to a gene implicated in virulence factor transport in other pathogens (virB11). A promoter for this operon, showing similarity to the Escherichia coli sigma70 consensus, was identified by primer extension. Cotranscription of the genes in the operon was demonstrated by reverse transcription-PCR, and transcription of virB11, fliI, fliQ, and murB was detected in human or mouse biopsies obtained from infected hosts. The genetic organization of this locus was conserved in a panel of H. pylori clinical isolates. Engineered fliI and fliQ mutant strains were completely aflagellate and nonmotile, whereas a virB11 mutant still produced flagella. The fliI and fliQ mutant strains produced reduced levels of flagellin and the hook protein FlgE. Production of OMP4, a member of the outer membrane protein family identified in H. pylori 26695, was reduced in both the virB11 mutant and the fliI mutant, suggesting related functions of the virulence factor export protein (VirB11) and the flagellar export component (FliI).

Evidence for ethnic tropism of Helicobacter pylori.

Helicobacter pylori infection in humans is linked to gastritis, gastric and duodenal ulcers, and gastric cancer. Peptic ulcer disease, as distinct from chronic asymptomatic infection, is strongly associated with expression of bacterial virulence markers, including a major antigen, CagA, and the vacuolating cytotoxin VacA. We have previously described significant differences in colonization rates, independent of socioeconomic status, among ethnic groups in New Zealand. To evaluate relative risks for peptic ulcer disease, we examined the frequency of two virulence markers in H. pylori strains infecting these ethnic groups. Although these markers occurred significantly more frequently in strains isolated from Polynesians than in strains from Europeans, this frequency was not reflected in the incidence of peptic ulcer disease in the two groups. DNA fingerprinting of the urease gene showed that Polynesians are more frequently infected by a group of strains which are genetically distinct from those affecting European New Zealanders. Our data suggest that separate bacterial lineages may have evolved in parallel with race-specific specialization.

Stimulation of interleukin-8 production in epithelial cell lines by Helicobacter pylori.

Following exposure to Helicobacter pylori cells, epithelial cell lines secreted interleukin-6 (IL-6) and IL-8 but not tumor necrosis factor alpha. Purified IL-6 alone did not stimulate IL-8 production from the cell lines tested, indicating that IL-6 was not an intermediary in IL-8 induction. Enhanced IL-8 secretion occurred in a time- and dose-dependent manner. None of 12 antibiotics tested exhibited a significant effect on IL-8-inducing activity, suggesting that preformed antigens were responsible for stimulating IL-8 secretion in vitro. Live bacterial cells caused the highest level of stimulation. Proteinase-digested and heated (56 or 100 degrees C) cells had significantly reduced stimulatory activities. Purified H. pylori lipopolysaccharide, but not exopolysaccharide, stimulated low-level secretion of IL-8, but only at high concentrations, while a water-extracted H. pylori antigen preparation was strongly stimulatory for HEp-2 cells. No reduction in IL-8-stimulatory activity was observed for H. pylori mutants negative for urease activity, production of a major lipoprotein, and motility. The noncytotoxic strain CCUG 915 stimulated lower IL-8 levels than other isolates. However, the otherwise isogenic cytotoxin-negative mutant 17874 delta vacA (S. H. Phadnis, D. Ilver, L. Janzon, S. Normark, and T. U. Westblom, Infect. Immun. 62:1557-1565, 1994) had the same IL-8-stimulatory ability as the parent strain, suggesting that surface proteins other than the vacuolating cytotoxin are involved in IL-8 stimulation.

The gamma-hemolysin locus of Staphylococcus aureus comprises three linked genes, two of which are identical to the genes for the F and S components of leukocidin.

The Staphylococcus aureus gamma-hemolysin comprises two polypeptides, whereas the gamma-hemolysin locus (hlg) contains three open reading frames. The hlgA and hlgB genes encode the gamma 1 and gamma 2 components, respectively. The HlgB protein (gamma 2) has 27% residue identity with S. aureus alpha-toxin. Surprisingly, hlgB and hlgC are 98.5 and 99.1% identical to the lukF and lukS genes, respectively, encoding the F and S components of the Panton-Valentine leukocidin.

Adhesive properties conferred by the plasminogen activator of Yersinia pestis.

A genomic library of Yersinia pestis EV76c created in a cosmid vector was screened for clones capable of binding type IV collagen. An unexpectedly high number of such clones was observed. One recombinant plasmid was selected for further study, and the locus controlling collagen binding was mapped by subcloning, transposon mutagenesis and exonuclease digestion. The outer-membrane protein profiles of transposon insertion mutants were correlated with phenotype to implicate a 36 kDa polypeptide in type IV collagen binding. Fine substructure restriction mapping and limited DNA sequence analysis showed the cloned locus to be identical to the locus (pla) for the plasminogen activator, previously characterized genetically and biochemically. The pla locus is resident on a 9.5 kb plasmid in wild-type Y. pestis strains. Curing of this plasmid resulted in negligible reduction in collagen-binding capacity, implying the existence of a chromosomally located determinant for collagen binding. The affinity of the plasminogen activator for collagen was relatively weak. When the cloned pla locus was introduced into E. coli, it conferred upon the cell the ability to bind to cells from a number of cell lines. Binding to glycolipids separated by thin-layer chromatography demonstrated that the receptor was a member of the globo-series of glycolipids. Since it has been reported that mutation of pla dramatically reduces virulence, we propose that this hitherto undescribed function of the gene product could contribute to the biological activities necessary for full virulence.

Rapid detection of Helicobacter pylori in gastric biopsy material by polymerase chain reaction.

By using primers based on the sequence of a species-specific antigen of Helicobacter pylori (P. O'Toole, S.M. Logan, M. Kostrzynska. T. Wadström, and T.J. Trust, J. Bacteriol. 173:505-513, 1991), a protocol was established for detection of this microorganism in gastric biopsy samples by the polymerase chain reaction (PCR). A single primer pair was used to specifically amplify a 298-bp sequence in a rapid two-step PCR. The primers exhibited the same specificity in PCR as that which we reported for the species-specific gene probe on which they were based. The sensitivity of the method was 20 copies of the target sequence, or 70 bacterial cells, under the lysis conditions used for patient-derived material. When amplification was performed for a saturating number of cycles, visual examination of ethidium bromide-stained gels successfully detected all samples subsequently judged to be positive by Southern hybridization of the gel with a probe specific for the PCR product. The bacterium could be detected in gastric biopsy samples from patients with various gastric diseases, including samples from which the bacterium could not be cultured. Only 9 of 19 patients who tested positive by PCR of gastric biopsy material were positive when a saliva sample was analyzed. Protocols for sample handling which minimized the risk of contamination while maximizing the sensitivity of the reaction were established. The results support a role for PCR in the rapid identification of H. pylori in clinical samples.

Nucleotide sequence of the epidermolytic toxin A gene of Staphylococcus aureus.

The nucleotide sequence of the eta gene, which codes for the epidermolytic toxin serotype A of Staphylococcus aureus TC16, is reported. The coding sequence of 840 nucleotides specifies a protein which, when secreted, has a predicted molecular weight of 26,950. The sequence of eta and the deduced amino acid sequence of the toxin have been compared with those of epidermolytic toxin serotype B. The coding sequences have 52% identical residues, and the polypeptides have 40% identical residues. Amino acid residues have been conserved in the areas of the proteins which correspond to major hydrophobic domains, whereas the regions likely to specify antigenic determinants occur in hydrophilic sequences that have diverged. The level of expression of epidermolytic toxin A in S. aureus 8325-4 was shown to be dependent on the integrity of a regulatory gene called agr.