Gut microbiota in adults with cystic fibrosis: Implications for the severity of the CFTR gene mutation and nutritional status.

BACKGROUND: Microbial dysbiosis has been linked to cystic fibrosis (CF); however, the composition of gut microbiota in adult CF patients in relation to severity of CF transmembrane conductance regulator (CFTR) gene mutation and nutritional status have not yet been explored. Study aimed to assess the gut microbiota composition in adults with CF, and its relationship with the severity of CFTR mutations, and BMI. METHODS: Gut microbiota of 41 adults with CF, and 26 non-CF controls were compared using whole 16S rRNA gene sequencing. Differences in the microbial community between groups of patients classified according to the severity of CFTR mutations, and BMI were assessed. The alpha diversity, beta diversity, and taxa abundance were identified to reflect gut microbiota composition. RESULTS: Results showed a significant decrease in alpha diversity of bacterial communities in CF compared to non-CF group, but no significant difference between the CF groups distinguished by the severity of CFTR mutations. However, more severe mutations were associated with the higher relative abundance of Bacteroides and Streptococcus and the lower relative abundance of Faecalibacterium and Blautia. Undernourished CF patients showed significantly lower alpha diversity compared to non-CF group and CF patients with BMI within the norm. Significant differences in the structure of the gut microbiota between CF and non-CF groups, as well as between BMI groups were also found. CONCLUSIONS: Our research indicates that CF is associated with alterations in gut microbiota in adults. Additionally, in adult CF patients, the composition of the gut microbiota is also related to BMI.

Why Does Your Uterus Become Malignant? The Impact of the Microbiome on Endometrial Carcinogenesis.

The aim of this review was to describe the uterine microbiome composition that has been analyzed so far and describe potential pathways in the carcinogenesis of the endometrium. The microbiome in the uterine environment is involved in apoptosis and proliferation during the menstruation cycle, pregnancy maintenance, and immune system support. However, bacteria in the uterus could stimulate inflammation, which when chronic results in malignancy. An altered gut microbiota initiates an inflammatory response through microorganism-associated molecular patterns, which leads to intensified steroidogenesis in the ovaries and cancers. Moreover, intestinal bacteria secreting the enzyme ß-glucuronidase may increase the level of circulating estrogen and, as a result, be influential in gynecological cancers. Both the uterine and the gut microbiota play a pivotal role in immune modulation, which is why there is a demand for further investigation from both the diagnostic and the therapeutic perspectives.

Catch-Up Growth as a Risk Factor for Rapid Weight Gain, Earlier Menarche and Earlier Pubertal Growth Spurt in Girls Born Small for Gestational Age (SGA)-A Longitudinal Study.

Most children born small for gestational age (SGA) have rapid postnatal growth. Despite its positive aspects, catch-up growth may affect the level of adipose tissue in the pre-pubertal and pubertal periods and therefore affect the age of puberty. The aim of this study was to determine the associations between size at birth, catch-up growth in infancy, BMI in peripubertal period, age at menarche, and the parameters of adolescent growth spurt of body height in girls born SGA. For 297 girls (22.6% SGA; 77.4% appropriate for gestational age (AGA)) complete body weight and height measurements and age at menarche were obtained. Adolescent growth spurt parameters were estimated using the JPA2 model (AUXAL SSI 3.1). Calculations were made in the Statistica 13 program using the Kruskal-Wallis and Kaplan-Meier tests. Girls born SGA with catch-up had the highest BMIs at the age of 8 years (H = 94.22, p < 0.001) and at menarche (H = 58.21, p < 0.001), experienced menarche earliest (H = 21.77, p < 0.001), same as the onset (H = 6.54, p = 0.012) and peak height velocity (H = 11.71, p = 0.003) of their adolescent growth spurt compared to SGA girls without catch-up and AGA girls. In SGA girls, catch-up growth has far-reaching consequences such as increased risk of fat accumulation and a rapid transition to puberty.

Mutations in GHR and IGF1R Genes as a Potential Reason for the Lack of Catch-Up Growth in SGA Children.

The aim of this review was to describe all of the mutations in the growth hormone receptor (GHR) and insulin-like growth factor-1 receptor (IGF1R) genes that have been discovered so far, and their possible impact on final body height, as well as their relationship with catch-up growth in children born small for gestational age (SGA). Mutations in the GHR gene were found to cause a body height below -2 SD, from the mean for sex and age, whereas the mutations in the IGF1R gene were associated with low body height and intrauterine growth restriction (IUGR), and with being born SGA. After birth, when the child's growth is not restricted by the intrauterine environment, the infant may develop its developmental potential and experience catch-up growth, which makes it possible to catch up with peers born appropriate for gestational age (AGA). Despite this, catch-up growth does not apply to all, but only to about 85% of SGA children, and its mechanism is unknown. It is possible that SGA children who did not experience catch-up growth are carriers of mutations in the GHR and/or IGF1R genes.

The Mediating Role of the Gut Microbiota in the Physical Growth of Children.

Gut microbiota succession overlaps with intensive growth in infancy and early childhood. The multitude of functions performed by intestinal microbes, including participation in metabolic, hormonal, and immune pathways, makes the gut bacterial community an important player in cross-talk between intestinal processes and growth. Long-term disturbances in the colonization pattern may affect the growth trajectory, resulting in stunting or wasting. In this review, we summarize the evidence on the mediating role of gut microbiota in the mechanisms controlling the growth of children.

The determinants of survival among adults with cystic fibrosis-a cohort study.

BACKGROUND: Cystic fibrosis (CF) is one of the most common autosomal recessive diseases. Factors contributing to disease exacerbations and survival rate of CF patients are type of mutation in the CFTR gene, poor nutritional status, lung failure, and infection development by Pseudomonas aeruginosa. The study aimed to evaluate the relationship between the severity of mutation, nutritional status, lung function, and Pseudomonas aeruginosa prevalence and survival rate in adult patients with cystic fibrosis. METHODS: A study of 124 (68 ♀ and 56 ♂) adults with CF aged 18-51 years were evaluated for (a) type of mutation in the CFTR gene, (b) nutritional status (BMI), (c) lung function (FEV1%), and (d) Pseudomonas aeruginosa prevalence. For statistical calculations, Kaplan-Meier analysis of survival, chi-squared test for multiple samples, and logistic regression were used. RESULTS: The type of mutation (χ2 = 12.73, df = 3, p = 0.005), FEV1% (χ2 = 15.20, df = 2, p = 0.0005), Pseudomonas aeruginosa prevalence (χ2 = 11.48, df = 3, p = 0.009), and BMI (χ2 = 31.08, df = 4, p < 0.000) significantly differentiated the probability of survival of patients with CF. The shortest life expectancy was observed in patients with a severe type of mutation on both alleles, FEV1% < 40, subjects in whom Pseudomonas culture was extensively drug-resistant or pandrug-resistant, and patients whose BMI was lower than 18.5 kg/m2. The period from 30 to 40 years of age was the most critical in CF adults' lifespan. The risk of adults with CF death doubled with Pseudomonas aeruginosa prevalence (OR = 2.06, 95% CI 1.29; 2.28) and eightfold when the bacteria acquired antibiotic resistance (OR = 8.11, 95% CI 1.67; 38.15). CONCLUSIONS: All factors included in the study were significantly related to the survival rate of patients with cystic fibrosis.

Pseudomonas aeruginosa, the type of mutation, lung function, and nutritional status in adults with cystic fibrosis.

OBJECTIVE: The aim of this study was to describe the relationship between the prevalence of Pseudomonas aeruginosa (PA) and lung function, as well as the nutritional status and type of gene mutation in adult patients with cystic fibrosis (CF). METHODS: This cross-sectional study evaluated 103 Polish adults with CF the following: • The occurrence of PA and the level of bacterial susceptibility to antibiotics; • Type of mutation in the CFTR gene; • Nutritional status assessed by body mass index (BMI), and • Lung function measured by forced expiratory volume in 1 s (FEV1%). RESULTS: The absence or presence of PA and the level of bacterial resistance were significantly related to the type of gene mutation (P < 0.001). In patients with a severe mutation, PA more often was extensively drug resistant or pandrug resistant compared with Pseudomonas culture-negative patients or patients with mild or unclassified mutations on both alleles. Associations were found between the presence of PA and lower values of BMI (P < 0.001), and FEV1% (P < 0.001). The risk for PA occurrence and the development of bacterial resistance increased twice in the case of severe mutation (odds ratio [OR], 2.51; 95% confidence interval [CI], 1.62-3.89), four times when BMI decreased <18.5 (OR, 4.15; 95% CI, 1.43-10.08). and six times when FEV1% fell <40 (OR, 6.75; 95% CI, 3.11-14.64). CONCLUSIONS: The presence of PA is associated with lower FEV1% and BMI values. Deterioration of lung function, undernutrition, and severe type of gene mutation are linked to a higher probability of PA acquisition and resistance to antibiotic treatment.

Time intervals between the age at menarche and the onset of sexual activity in Polish women born between 1959 and 2001.

OBJECTIVES: The aim of this study was to assess time intervals between the age at menarche (AM) and age at sexual initiation (ASI) in Polish women born before and after the political transformation period in Poland. METHODS: Participants were 518 women born between 1959 and 2001 in Poland. AM and ASI were based on self-report. Three birth cohorts were distinguished based on the year of birth: I (1959-1979), II (1980-1989), III (1990-2001). Three categories of AM were distinguished: early maturing (<12.0 years), average (12.0-13.0 years), and late maturing (≥14.0 years). Temporal intervals between AM and ASI were calculated. RESULTS: Both AM and ASI decreased in subsequent birth cohorts, with the greatest changes observed in the women born after 1989. No significant differences in the time interval between AM and ASI were observed between birth cohorts. However, the time interval between AM and ASI differed by AM category (H = 74.16; P < .001). The longest time period between AM and ASI occurred in early maturing girls (7.13 years) and the shortest in late maturing girls (3.25 years). CONCLUSIONS: Despite the transformation and decline in both AM and ASI, the time interval between these two characteristics remained stable. Significant differences in the time interval were found among women stratified by AM. The time interval between AM and ASI was longer in girls who matured early in comparison to those maturing late or at the average time.

Application of auxological methods, including dental age estimation, in the assessment of delayed puberty in girls in gynecological practice.

Developmental gynecology uses methods practiced in auxology - the science of human ontogenetic development.An important and jointly used concept in gynecology and auxology is the concept of developmental age, which, unlikecalendar age, is a measure of the biological maturity of the organism, indicating the stage of advancement in the developmentof certain features or body systems. Developmental age assessment methods include: a) morphological (somatic)age - body height and weight, b) secondary sex characteristics - breast in girls, genitalia (penis and testes) in boys, andpubic hair in both sexes, c) bone age - hand and wrist x-ray, and d) dental age. An important marker of developmentalage is also age at menarche, treated as a late indicator of puberty in girls. All of these methods are useful in the context ofassessing regularity and disorders of puberty, such as delayed puberty. The paper discusses developmental age assessmentmethods that can be used to diagnose delayed puberty as well as the causes of delayed puberty in girls. It should be emphasizedthat in assessing the process of physical development of a given individual, the cooperation of specialists in the fieldof developmental gynecology, pediatrics, auxology, dentistry, endocrinology, and dietetics would be the most desirable.

BMI at menarche and timing of growth spurt and puberty in Polish girls - longitudinal study.

Objectives: The purpose of the study was to evaluate the relationship between BMI at menarche and selected growth spurt parameters, such as age at take-off of the pubertal growth spurt (ATO), age at peak height velocity (APHV), growth spurt duration (APHV-ATO), and the pubertal growth rate. Methods: The study group consisted of 243 girls aged 10-16 years. Several measurements of body height and weight have been taken for each girl during the girls' development (longitudinal study). Nutritional status has been assessed using the IOTF (Cole et al. 2000; Cole et al. 2007). Girls were asked about their age at menarche. To investigate the growth rate, the age at TO and PHV for each girl was calculated using AUXAL.3 software and a structural model JPA2. Statistical analyses were made in Statistica 12.0 using Kruskal-Wallis test Kruskal-Wallis test and multiple regression analysis. Results: The mean age at menarche for the entire group was 12.59 (Me = 12.52, Min = 9.9, Max = 16.2). There was a significant statistical relationship between the level of BMI and age at menarche. The age at menarche decreased significantly with increasing levels of nutritional status (H = 33.2, p < 0.001). Also, TO and PHV occurred earlier in girls with higher values of BMI indicator (TO: H = 12.25, p < 0.05; PHV: H = 12.25, p < 0.05). Conclusions: The level of nutritional status at the age of menarche is significantly related to growth and the rate of biological maturation in girls. Higher BMI at menarche is associated with an earlier occurrence of menarche, TO and PHV.

Trends over time in age at sexual debut among Polish women and underlying socio-economic determinants.

ABSTRACT: The aim of the study was to evaluate (1) changes over time in age at sexual initiation among Polish women and (2) underlying socio-economic determinants. 273 women born between 1975 and 1995 in Wielkopolska region (Poland) filled in a questionnaire of sexual behavior. The questionnaire included questions about the age of sexual initiation and women's socio-economic status such as place of residence, level of education, type of school, marital status. Database and statistical analyzes were performed using Statistica 10.0. Age of sexual initiation differed significantly among the cohorts of women stratified by birth cohort (H = 61.4, p < 0.001). In cohort I (born between 1970-1975), mean age of initiation was 18.97 years, in cohort II (1976-1980) 18.67 years, in cohort III (1981-1985) 18.53 years; cohort IV (1986-1990) 18.27 years, and cohort V (1991-1995) 16.41 years. Two socio-economic variables significantly affected the age of the sexual activity onset: the type of school and level of education. The mean age of sexual debut among Polish women has significantly decreased over the last 40 years, with the largest, statistically significant difference observed between the most recent cohort of women (born between 1991-1995) and the other cohorts (born between 1970-1990). The most significant socio-economic determinants of age at first sex were the type of school and level of education.