Intestinal microbiota and vaccine efficacy in children from resource poor settings - potential impact for the usefulness of probiotics?

Developing countries continue to contribute significantly to the global burden of childhood mortality due to infectious diseases. Infections leading to diseases like diarrhoea, pneumonia and meningitis account for millions of deaths annually. Most of these diseases are preventable by vaccination and therefore global vaccination rates have risen substantially with clear benefits. But paradoxically, the vaccines have demonstrated lower immunogenicity in developing countries as compared to their industrialised counterparts. Malnutrition in resource poor settings along with repeated polymicrobial infections at early age are some of the reasons for the differences in vaccine efficacy in different settings. Recent studies indicate that the gastrointestinal microbiota possibly influences maturation of immune system as well as vaccine efficacy. In this review we discuss evidences from in vitro, animal and human studies showing that probiotics can positively modulate gut microbiota composition and exert immunomodulatory effects on the host. We also discuss how they should be evaluated for their ability to improve vaccine performance especially in low resource settings.

Visual and cutaneous triggering of rapid step initiation.

The effects of a cutaneous imperative stimulus trigger cue (sural nerve stimulation) versus visual cuing of rapid step initiation were assessed in young, healthy subjects (n = 18). Two sets of experiments were conducted in which the vertical ground reaction force and EMG in tibialis anterior (TA) and gluteus medius (GM) were recorded in nine subjects and the vertical ground reaction force and center of pressure were recorded in a separate group of nine subjects. Subjects stood with one foot on a force platform with weight equally distributed and asked to take three steps as quickly as possible. A visual ready signal was followed at random times (0.5-2 s) by either a second visual go cue or stimulation of the sural nerve. Results revealed that sural cuing produced: (1) earlier onset times, greater vertical ground reaction forces and a greater rate of rise of force, (2) earlier onsets of TA and GM and greater mean EMG amplitudes in these muscles and (3) greater COP displacements in both the posterior and lateral direction. These results confirm previous reports on the functions of TA and GM in step initiation and further show that sural cuing enhances these EMG responses and the subsequent kinetic and kinematic changes associated with them.

Carbohydrate induced modulation of cell membrane VII. Binding of exogenous lectin increases osmofragility of erythrocytes.

Due to their multivalent binding character, lectins when added exogenously will cross-link membrane surface receptors leading to lateral molecular reorganizations in the plane of the bilayer. This study reports for the first time that agglutination of rabbit erythrocytes by lentil lectin and concanavalin A increases their osmofragility. Increase in osmofragility was detected by measuring the hemolysis of erythrocytes in hypotonic as well as in isotonic solutions. It was also found that agglutination per se does not increase osmofragility but the binding of legume lectin is essential since human Rh+ cells agglutinated by a monoclonal antibody do not exhibit hemolysis.

Distribution of fitness effects caused by random insertion mutations in Escherichia coli.

Very little is known about the distribution of mutational effects on organismal fitness, despite the fundamental importance of this information for the study of evolution. This lack of information reflects the fact that it is generally difficult to quantify the dynamic effects of mutation and natural selection using only static distributions of allele frequencies. In this study, we took a direct approach to measuring the effects of mutations on fitness. We used transposon-mutagenesis to create 226 mutant clones of Escherichia coli. Each mutant clone carried a single random insertion of a derivative of Tn10. All 226 mutants were independently derived from the same progenitor clone, which was obtained from a population that had evolved in a constant laboratory environment for 10,000 generations. We then performed competition experiments to measure the effect of each mutation on fitness relative to a common competitor. At least 80% of the mutations had a significant negative effect on fitness, whereas none of the mutations had a significant positive effect. The mutations reduced fitness by about 3%, on average, but the distribution of fitness effects was highly skewed and had a long, flat tail. A compound distribution, which includes both gamma and uniform components, provided an excellent fit to the observed fitness values.