Gut bacteria at 6 months of age are associated with immune cell status in 1-year-old children.

Age-related gut bacterial changes during infancy have been widely studied, but it remains still unknown how these changes are associated with immune cell composition. This study's aim was to explore if the temporal development of gut bacteria during infancy prospectively affects immune cell composition. Faecal bacteria and short-chain fatty acids were analysed from 67 PreventADALL study participants at four timepoints (birth to 12 months) using reduced metagenome sequencing and gas chromatography. Immune cell frequencies were assessed using mass cytometry in whole blood samples at 12 months. The infants clustered into four groups based on immune cell composition: clusters 1 and 2 showed a high relative abundance of naïve cells, cluster 3 exhibited increased abundance of classical- and non-classical monocytes and clusters 3 and 4 had elevated neutrophil levels. At all age groups, we did observe significant associations between the gut microbiota and immune cell clusters; however, these were generally from low abundant species. Only at 6 months of age we observed significant associations between abundant (>8%) species and immune cell clusters. Bifidobacterium adolescentis and Porphyromonadaceae are associated with cluster 1, while Bacteroides fragilis and Bifidobacterium longum are associated with clusters 3 and 4 respectively. These species have been linked to T-cell polarization and maturation. No significant correlations were found between short-chain fatty acids and immune cell composition. Our findings suggest that abundant gut bacteria at 6 months may influence immune cell frequencies at 12 months, highlighting the potential role of gut microbiota in shaping later immune cell composition.

A Globally Distributed Bacteroides caccae Strain Is the Most Prevalent Mother-Child Shared Bacteroidaceae Strain in a Large Scandinavian Cohort.

Bacteroides and Phocaeicola, members of the family Bacteroidaceae, are among the first microbes to colonize the human infant gut. While it is known that these microbes can be transmitted from mother to child, our understanding of the specific strains that are shared and potentially transmitted is limited. In this study, we aimed to investigate the shared strains of Bacteroides and Phocaeicola in mothers and their infants. We analyzed fecal samples from pregnant woman recruited at 18 weeks of gestation from the PreventADALL study, as well as offspring samples from early infancy, including skin swab samples taken within 10 min after birth, the first available fecal sample (meconium), and fecal samples at 3 months of age. We screened 464 meconium samples for Bacteroidaceae, with subsequent selection of 144 mother-child pairs for longitudinal analysis, based on the presence of Bacteroidaceae, longitudinal sample availability, and delivery mode. Our results showed that Bacteroidaceae members were mainly detected in samples from vaginally delivered infants. We identified high prevalences of Phocaeicola vulgatus, Phocaeicola dorei, Bacteroides caccae, and Bacteroides thetaiotaomicron in mothers and vaginally born infants. However, at the strain level, we observed high prevalences of only two strains: a B. caccae strain and a P. vulgatus strain. Notably, the B. caccae strain was identified as a novel component of mother-child shared strains, and its high prevalence was also observed in publicly available metagenomes worldwide. Our findings suggest that mode of delivery may play a role in shaping the early colonization of the infant gut microbiota, in particular the colonization of Bacteroidaceae members. IMPORTANCE Our study provides evidence that Bacteroidaceae strains present on infants' skin within 10 min after birth, in meconium samples, and in fecal samples at 3 months of age in vaginally delivered infants are shared with their mothers. Using strain resolution analyses, we identified two strains, belonging to Bacteroides caccae and Phocaeicola vulgatus, as shared between mothers and their infants. Interestingly, the B. caccae strain showed a high prevalence worldwide, while the P. vulgatus strain was less common. Our findings also showed that vaginal delivery was associated with early colonization of Bacteroidaceae members, whereas cesarean section delivery was associated with delayed colonization. Given the potential for these microbes to influence the colonic environment, our results suggest that understanding the bacterial-host relationship at the strain level may have implications for infant health and development later in life.

Treatment of overweight and obesity in general practice: a cluster randomised trial.

Overweight and obesity are among the most serious health problems of our time. A majority of patients with overweight and obesity will first get in touch with health services through primary care. This makes it crucial to develop strategies to enable physicians in primary care to help and treat patients with overweight and obesity. The physicians tend to avoid this subject. The main reason is reported to be lack of knowledge and education, and that they have nothing concrete to offer their patients. We wanted to examine if a simple method with specific measures could be used in Norwegian general practice and achieve meaningful weight loss. 23 physicians and 210 patients participated in the study. The physicians who participated were cluster randomised into either control group or intervention group. The physicians in the control group were told to follow their usual approach, while the physicians in the intervention group followed a fixed plan with specific diets given orally and in writing to the patients. The inclusion criteria for both groups were: body mass index (BMI)>30 kg/m2, or BMI>25 kg/m2 with at least one weight-related condition. Weight was measured at the start, then after 1 year and finally after 2 years in both groups. We found no significant weight loss in the control group. In the intervention group, there was a weight loss of at least 10% by 25.5% after the first year and 24.2% after the entire observation period. 53.5% of the patients lost at least 5% of their weight in the first year and nearly 45% after the entire observation period. We conclude that a simple tool with a specific diet and activity plan is feasible in general practice and may produce significant weight loss. Trial registration number: NCT03000062.

Fecal Microbiota Nutrient Utilization Potential Suggests Mucins as Drivers for Initial Gut Colonization of Mother-Child-Shared Bacteria.

The nutritional drivers for mother-child sharing of bacteria and the corresponding longitudinal trajectory of the infant gut microbiota development are not yet completely settled. We therefore aimed to characterize the mother-child sharing and the inferred nutritional utilization potential for the gut microbiota from a large unselected cohort. We analyzed in depth gut microbiota in 100 mother-child pairs enrolled antenatally from the general population-based Preventing Atopic Dermatitis and Allergies in Children (PreventADALL) cohort. Fecal samples collected at gestational week 18 for mothers and at birth (meconium), 3, 6, and 12 months for infants were analyzed by reduced metagenome sequencing to determine metagenome size and taxonomic composition. The nutrient utilization potential was determined based on the Virtual Metabolic Human (VMH, www.vmh.life) database. The estimated median metagenome size was ∼150 million base pairs (bp) for mothers and ∼20 million bp at birth for the children. Longitudinal analyses revealed mother-child sharing (P < 0.05, chi-square test) from birth up to 6 months for 3 prevalent Bacteroides species (prevalence, >25% for all age groups). In a multivariate analysis of variance (ANOVA), the mother-child-shared Bacteroides were associated with vaginal delivery (1.7% explained variance, P = 0.0001). Both vaginal delivery and mother-child sharing were associated with host-derived mucins as nutrient sources. The age-related increase in metagenome size corresponded to an increased diversity in nutrient utilization, with dietary polysaccharides as the main age-related factor. Our results support host-derived mucins as potential selection means for mother-child sharing of initial colonizers, while the age-related increase in diversity was associated with dietary polysaccharides.IMPORTANCE The initial bacterial colonization of human infants is crucial for lifelong health. Understanding the factors driving this colonization will therefore be of great importance. Here, we used a novel high-taxonomic-resolution approach to deduce the nutrient utilization potential of the infant gut microbiota in a large longitudinal mother-child cohort. We found mucins as potential selection means for the initial colonization of mother-child-shared bacteria, while the transition to a more adult-like microbiota was associated with dietary polysaccharide utilization potential. This knowledge will be important for a future understanding of the importance of diet in shaping the gut microbiota composition and development during infancy.

De novo species identification using 16S rRNA gene nanopore sequencing.

Nanopore sequencing is rapidly becoming more popular for use in various microbiota-based applications. Major limitations of current approaches are that they do not enable de novo species identification and that they cannot be used to verify species assignments. This severely limits applicability of the nanopore sequencing technology in taxonomic applications. Here, we demonstrate the possibility of de novo species identification and verification using hexamer frequencies in combination with k-means clustering for nanopore sequencing data. The approach was tested on the human infant gut microbiota of 3-month-old infants. Using the hexamer k-means approach we identified two new low abundant species associated with vaginal delivery. In addition, we confirmed both the vaginal delivery association for two previously identified species and the overall high levels of bifidobacteria. Taxonomic assignments were further verified by mock community analyses. Therefore, we believe our de novo species identification approach will have widespread application in analyzing microbial communities in the future.

Butyrate Levels in the Transition from an Infant- to an Adult-Like Gut Microbiota Correlate with Bacterial Networks Associated with Eubacterium Rectale and Ruminococcus Gnavus.

Relatively little is known about the ecological forces shaping the gut microbiota composition during infancy. Therefore, the objective of the present study was to identify the nutrient utilization- and short-chain fatty acid (SCFA) production potential of gut microbes in infants during the first year of life. Stool samples were obtained from mothers at 18 weeks of pregnancy and from infants at birth (first stool) at 3, 6, and 12-months of age from the general population-based PreventADALL cohort. We identified the taxonomic and SCFA composition in 100 mother-child pairs. The SCFA production and substrate utilization potential of gut microbes were observed by multiomics (shotgun sequencing and proteomics) on six infants. We found a four-fold increase in relative butyrate levels from 6 to 12 months of infant age. The increase was correlated to Eubacterium rectale and its bacterial network, and Faecalibacterium prausnitzii relative abundance, while low butyrate at 12 months was correlated to Ruminococcus gnavus and its associated network of bacteria. Both E. rectale and F. prausnitzii expressed enzymes needed for butyrate production and enzymes related to dietary fiber degradation, while R. gnavus expressed mucus-, fucose, and human milk oligosaccharides (HMO)-related degradation enzymes. Therefore, we believe that the presence of E. rectale, its network, and F. prausnitzii are key bacteria in the transition from an infant- to an adult-like gut microbiota with respect to butyrate production. Our results indicate that the transition from an infant- to an adult-like gut microbiota with respect to butyrate producing bacteria, occurs between 6 and 12 months of infant age. The bacteria associated with the increased butyrate ratio/levels were E. rectale and F. prausnitzii, which potentially utilize a variety of dietary fibers based on the glycoside hydrolases (GHs) expressed. R. gnavus with a negative association to butyrate potentially utilizes mucin, fucose, and HMO components. This knowledge could have future importance in understanding how microbial metabolites can impact infant health and development.

Effectiveness of using STOPP/START criteria to identify potentially inappropriate medication in people aged ≥ 65 years with chronic kidney disease: a randomized clinical trial.

PURPOSE: Polypharmacy and inappropriate prescribing are common in elderly with chronic kidney disease (CKD). This study identified potentially inappropriate prescriptions (PIPs) and potential prescribing omissions (PPOs) using the Screening Tool of Older Persons' Prescriptions (STOPP) and the Screening Tool to Alert doctors to the Right Treatment (START) criteria in elderly with advanced CKD and determined the effect of a medication review on medication adherence and health-related quality of life (HRQoL). METHODS: The intervention consisted of a medication review using STOPP/START criteria with a recommendation to a nephrologist or similar review without a recommendation. End points were prevalence of PIP and PPO, medication adherence, and HRQoL. Group differences in outcomes were assessed using a generalized linear mixed model. The trial was registered under www.clinicaltrial.gov (ID: NCT02424786). RESULTS: We randomized 180 patients with advanced CKD (mean age 77 years, 23% female). The prevalence of PIPs and PPOs in the intervention group was 54% and 50%, respectively. The odds of PPOs were lower in the intervention than the control group (OR 0.42, 95% CI 0.19-0.92, p = 0.032), while there was no intergroup difference in the number of PIPs (OR 0.57, CI 0.27-1.20, p = 0.14). There was no difference in changes in medication adherence or HRQoL from baseline to 6 months between the groups. CONCLUSIONS: The intervention with the STOPP/START criteria identified a high prevalence of inappropriate medications in the elderly with advanced CKD and reduced the number of PPOs. However, there was no detectable impact of the intervention on medication adherence or HRQoL.

Medication regimen complexity and medication adherence in elderly patients with chronic kidney disease.

INTRODUCTION: Elderly patients with chronic kidney disease (CKD) stage 5 with or without dialysis treatment usually have concomitant comorbidities, which often result in multiple pharmacological therapies. This study aimed to identify factors associated with medication complexity and medication adherence, as well as the association between medication complexity and medication adherence, in elderly patients with CKD. METHODS: This prospective study involved elderly patients with CKD stage 5 (estimated glomerular filtration rate < 15 ml/min/1.73m2 ) recruited from three Norwegian hospitals. Most of the patients were receiving either hemodialysis or peritoneal dialysis. We used the Medication Regimen Complexity Index (MRCI) to assess the complexity of medication regimens, and the eight-item Morisky Medication Adherence Scale (MMAS-8) to assess medication adherence. Factors associated with the MRCI and MMAS-8 score were determined using either multivariable linear or ordinal logistic regression analysis. FINDINGS: In total, 157 patients aged 76 ± 7.2 years (mean ± SD) were included in the analysis. Their overall MRCI score was 22.8 ± 7.7. In multivariable linear regression analyses, female sex (P = 0.044), Charlson Comorbidity Index of 4 or 5 (P = 0.029) and using several categories of phosphate binders (P < 0.001 to 0.04) were associated with the MRCI. Moderate or high adherence (MMAS-8 score ≥ 6) was demonstrated by 83% of the patients. The multivariable logistic regression analyses found no association of medication complexity, age or other variables with medication adherence as assessed using the MMAS-8. DISCUSSION: Female sex, comorbidity and use of phosphate binders were associated with more-complex medication regimens in this population. No association was found between medication regimen complexity, phosphate binders or age and medication adherence. These findings are based on a homogeneous elderly group, and so future studies should test if they can be generalized to patients of all ages with CKD.

More potent lipid-lowering effect by rosuvastatin compared with fluvastatin in everolimus-treated renal transplant recipients.

BACKGROUND: Dyslipidemia is a risk factor for premature cardiovascular morbidity and mortality in renal transplant recipients (RTRs). Pharmacotherapy with mTOR inhibitors aggravates dyslipidemia, thus necessitating lipid-lowering therapy with fluvastatin, pravastatin, or atorvastatin. These agents may not sufficiently lower lipid levels, and therefore, a more potent agent like rosuvastatin maybe needed. METHODS: We have aimed to assess the lipid-lowering effect of rosuvastatin as compared with fluvastatin in RTR receiving everolimus. Safety was assessed as the pharmacokinetic (PK) interaction potential of a rosuvastatin/everolimus combination in RTR. A 12-hour everolimus PK investigation was performed in 12 stable RTR receiving everolimus and fluvastatin (80 mg/d). Patients were then switched to rosuvastatin (20 mg/d), and a follow-up 12/24-hour PK investigation of everolimus/rosuvastatin was performed after 1 month. All other drugs were kept unchanged. RESULTS: In RTR already receiving fluvastatin, switching to rosuvastatin further decreased LDL cholesterol and total cholesterol by 30.2±12.2% (P<0.01) and 18.2±9.6% (P<0.01), respectively. Everolimus AUC0-12 was not affected by concomitant rosuvastatin treatment, 80.3±21.3 µg*h/L before and 78.5±21.9 µg*h/L after, respectively (P=0.61). Mean rosuvastatin AUC0-24 was 157±61.7 ng*h/mL, approximately threefold higher than reported in the literature for nontransplants. There were no adverse events, and none of the patients had or developed proteinuria. CONCLUSION: Rosuvastatin showed a superior lipid-lowering effect compared to fluvastatin in stable RTR receiving everolimus. The combination of everolimus/rosuvastatin seems to be as safe as the everolimus/fluvastatin combination.

Lecithin: Cholesterol Acyltransferase (LCAT) Deficiency: renal lesions with early graft recurrence.

Familial lecithin:cholesterol acyltransferase (LCAT) deficiency is a rare metabolic disease with lipid deposition in several organs. The authors report a man with hypertension and proteinuria. Renal biopsy revealed glomerular changes, including peculiar thrombus-like deposits, consistent with LCAT deficiency. He was found to be compound heterozygous for two mutations of the LCAT gene. He received a kidney graft from his father. The authors also describe LCAT deficiency-related lesions in the explanted native kidneys and in biopsies at 2 days, 6 weeks, and 1 year after transplantation. The morphology of this disease is characteristic, and the diagnosis should be suspected from the ultrastructural findings.