Obesity risk rises if antibiotics given before age two

The research in the Journal of the American Medical Association (JAMA) Pediatrics is the latest to find a link between weight problems and antibiotics, which can eliminate bacterial infections but also the beneficial intestinal microflora that colonizes the gut.
Experts at the Children's Hospital of Philadelphia looked at health records from nearly 65,000 children who were treated at primary care clinics from 2001 to 2013. Those included in the study were followed for five years.
More than two thirds of the kids studied were exposed to antibiotics before age two. The increase in obesity risk ranged from two to 20 percent and was seen particularly in children who had been treated with antibiotics four or more times by age two.
Those given broad-spectrum antibiotics, which target a range of bacteria, were also at higher risk of weight problems in childhood.

"No association was seen between obesity and narrow-spectrum antibiotics," said the study, which described the use of broad-spectrum antibiotics in children under two as "one factor" in whether a child develops obesity.

Skeletal Muscle PGC-1α1 Modulates Kynurenine Metabolism and Mediates Resilience to Stress-Induced Depression.

Depression is a debilitating condition with a profound impact on quality
of life for millions of people worldwide. Physical exercise is used as a
treatment strategy for many patients, but the mechanisms that underlie
its beneficial effects remain unknown. Here, we describe a mechanism by
which skeletal muscle PGC-1α1 (PPARGC1A)induced by exercise training changes
kynurenine metabolism and protects from stress-induced depression.
Activation of the PGC-1α1-PPARα/δ pathway increases skeletal muscle
expression of kynurenine aminotransferases, thus enhancing the
conversion of kynurenine into kynurenic acid, a metabolite unable to
cross the blood-brain barrier. Reducing plasma kynurenine protects the
brain from stress-induced changes associated with depression and renders
skeletal muscle-specific PGC-1α1 transgenic mice resistant to
depression induced by chronic mild stress or direct kynurenine
administration. This study opens therapeutic avenues for the treatment
of depression by targeting the PGC-1α1-PPAR axis in skeletal muscle,
without the need to cross the blood-brain barrier.

Cytomegalovirus seropositivity is negatively associated with multiple sclerosis.


Epidemiological data suggest a
role for common viruses in the pathogenesis of multiple sclerosis (MS),
and recent data showed a negative association of past cytomegalovirus
(CMV) infection on pediatric MS risk.


Our aim was to analyze the association of CMV infection with MS risk in an adult
case-control material. A meta-analysis was performed to validate our findings.


Epidemiological Investigation in MS (EIMS) is a case-control study with incident cases and population-based controls. Anti-CMV antibody titers were measured with ELISA, and HLA-A
and DRB1 genotyping was performed with SSP-PCR, in 658 MS cases, who all fulfilled the McDonald criteria for MS, and 786 controls.


CMV seropositivity was associated with a decreased MS risk, OR = 0.73
(0.58-0.92 95% CI), p = 0.005, adjusted for index age, gender, smoking,
sun exposure, EBNA1 IgG titer and HLA-A*02 and DRB1*15. When we removed
all cases and controls younger than 18 years at index, the protective
effect was still apparent.


CMV is negatively associated with adult-onset MS pathology, consistent with results from a
study on pediatric MS cases. It remains to be shown whether this
negative association is due to a true protective effect of CMV infection
on MS risk.

Associations of the Fecal Microbiome With Urinary Estrogens and Estrogen Metabolites in Postmenopausal Women: The Journal of Clinical Endocrinology & Metabolism: Vol 0, No 0

The gut microbiota may influence the risk of breast cancer through effects on endogenous estrogens.

The objective of the study was to investigate whether urinary estrogens and
estrogen metabolites are associated with the diversity and composition
of the fecal microbiome.

This was a cross-sectional study among women enrolled in Kaiser Permanente of Colorado.

A total of 60 women drawn from a random sample of healthy postmenopausal  women (aged 55–69 y), without current or recent use of antibiotics or  hormone therapy and no history of cancer or gastrointestinal disease  participated in the study.

Creatinine-standardized urinary estrogens (estrone and estradiol) and 13 hydroxylated estrogen
metabolites were measured in spot urines by liquid chromatography-tandem mass spectrometry. The fecal microbiome was assessed using  pyrosequencing of 16S rRNA amplicons. General linear models were used to test for associations of diversity and composition of the fecal  microbiome with parent estrogen (estrone + estradiol), total estrogens,  and estrogen metabolites and the ratio of estrogen metabolites to parent estrogen, which has been predictive of postmenopausal breast cancer  risk in previous studies.

The ratio of metabolites to parents was directly associated with whole-tree phylogenetic diversity (R = 0.35, P= .01). Relative abundances of the order Clostridiale (R = 0.32, P= .02) and the genus Bacteroides (R = -0.30, P= .03) were also correlated with the ratio of metabolites to parents.
Associations were independent of age, body mass index, and study design  factors.

Our data suggest that women with a more diverse gut microbiome exhibit an  elevated urinary ratio of hydroxylated estrogen metabolites to parent  estrogen. Further research is warranted to confirm and relate these  findings to clinical disease.

Mothers of children with autism less likely to have taken iron supplements in pregnancy, study shows -- ScienceDaily

Low iron intake was associated with a five-fold greater risk of autism
in the child if the mother was 35 or older at the time of the child's
birth or if she suffered from metabolic conditions such as obesity
hypertension or diabetes.

Blood test may help determine who is at risk for psychosis -- ScienceDaily

A blood test, when used in psychiatric patients experiencing symptoms
that are considered to be indicators of a high risk for psychosis,
identifies those who later went on to develop psychosis, preliminary
results of a new study show. "The blood test included a selection of 15
measures of immune and hormonal system imbalances as well as evidence of
oxidative stress," explained a corresponding author of the study.

Here's the paper:-
Towards a Psychosis Risk Blood Diagnostic for Persons Experiencing High-Risk Symptoms: Preliminary Results From the NAPLS Project

Healthy humans make nice homes for viruses Washington University in St. Louis

On average, healthy individuals carry about five types of viruses on their bodies, the researchers report online in BioMed Central Biology. The study is the first comprehensive analysis to describe the diversity of viruses in healthy people.

The research was conducted as part of the Human Microbiome Project, a major initiative funded by the National Institutes of Health (NIH) that largely has focused on cataloging the body’s bacterial ecosystems.
Analyzing the samples, the scientists found seven families of viruses, including strains of herpes viruses that are not sexually transmitted. For example, herpesvirus 6 or herpesvirus 7 was found in 98 percent of individuals sampled from the mouth. Certain strains of papillomaviruses were found in about 75 percent of skin samples and 50 percent of samples from the nose. Novel strains of the virus were found in both sites.
Not surprisingly, the vagina was dominated by papillomaviruses, with 38 percent of female subjects carrying such strains. Some of the women harbored certain high-risk strains that increase the risk of cervical cancer. These strains were more common in women with communities of vaginal bacteria that had lower levels of Lactobacillus and an increase in bacteria such as Gardnerella, which is associated with bacterial vaginosis.
Adenoviruses, the viruses that cause the common cold and pneumonia, also were common at many sites in the body.

Opposite risk patterns for autism and schizophrenia are associated with normal variation in birth size: phenotypic support for hypothesized diametric gene-dosage effects.

Opposite phenotypic and behavioural traits associated with copy number
variation and disruptions to imprinted genes with parent-of-origin
effects have led to the hypothesis that autism and schizophrenia share
molecular risk factors and pathogenic mechanisms, but a direct
phenotypic comparison of how their risks covary has not been attempted.
Here, we use health registry data collected on Denmark's roughly 5
million residents between 1978 and 2009 to detect opposing risks of
autism and schizophrenia depending on normal variation (mean ± 1 s.d.)
in adjusted birth size, which we use as a proxy for diametric
gene-dosage variation in utero. Above-average-sized babies (weight,
3691-4090 g; length, 52.8-54.3 cm) had significantly higher risk for
autism spectrum (AS) and significantly lower risk for schizophrenia
spectrum (SS) disorders. By contrast, below-average-sized babies
(2891-3290 g; 49.7-51.2 cm) had significantly lower risk for AS and
significantly higher risk for SS disorders. This is the first study
directly comparing autism and schizophrenia risks in the same
population, and provides the first large-scale empirical support for the
hypothesis that diametric gene-dosage effects contribute to these
disorders. Only the kinship theory of genomic imprinting predicts the
opposing risk patterns that we discovered, suggesting that molecular
research on mental disease risk would benefit from considering
evolutionary theory.

A mycotoxin present in many types of food deteriorates neuroregeneration

chemical structure of the mycotoxin ochratoxin A
chemical structure of the mycotoxin ochratoxin A (Photo credit: Wikipedia)
Researchers at the Institute for Biomedical Sciences at CEU-UCH, in
cooperation with colleagues of University of Valencia, showed through in
vitro as well as in vivo experiments on lab animals the potential
negative effect on neuroregeneration caused by Ochratoxine A, a
mycotoxine found in many types of food, especially cereals and their
derivatives. The study showed that Ochratoxine A deteriorates the
formation of new neurons in the brain, a process called neurogenesis
that, in particular, takes place in the subventricular zone, which in
the adult brain is the largest of the neurogenic zones.

Air Pollution and Children: Neural and Tight Junction Antibodies and Combustion Metals, the Role of Barrier Breakdown and Brain Immunity in Neurodegeneration.

Millions of children are exposed to concentrations of air pollutants, including fine particulate matter (PM2.5), above safety standards. Mexico City Metropolitan Area (MCMA) megacity children show an early brain imbalance in oxidative stress, inflammation, innate and adaptive immune response-associated genes, and blood-brain barrier breakdown. We investigated serum and cerebrospinal fluid (CSF) antibodies to neural and tight junction proteins and environmental pollutants in 139 children ages 11.91 ± 4.2 y with high versus low air pollution exposures. We also measured metals in serum and CSF. MCMA children showed significantly higher serum actin IgG, occludin/zonulin 1 IgA, IgG, myelin oligodendrocyte glycoprotein IgG and IgM (p < 0.01), myelin basic protein IgA and IgG, S-100 IgG and IgM, and cerebellar IgG (p < 0.001). Serum IgG antibodies to formaldehyde, benzene, and bisphenol A, and concentrations of Ni and Cd were significantly higher in exposed children (p < 0.001). CSF MBP antibodies and nickel concentrations were higher in MCMA children (p = 0.03). Air pollution exposure damages epithelial and endothelial barriers and is a robust trigger of tight junction and neural antibodies. Cryptic 'self' tight junction antigens can trigger an autoimmune response potentially contributing to the neuroinflammatory and Alzheimer and Parkinson's pathology hallmarks present in megacity children. The major factor determining the impact of neural antibodies is the integrity of the blood-brain barrier. Defining the air pollution linkage of the brain/immune system interactions and damage to physical and immunological barriers with short and long term neural detrimental effects to children's brains ought to be of pressing importance for public health.

Artificial sweeteners linked to abnormal glucose metabolism

Artificial sweeteners, promoted as aids to weight loss and diabetes
prevention, could actually hasten the development of glucose intolerance
and metabolic disease; and they do it in a surprising way: by changing
the composition and function of the gut microbiota – the substantial
population of bacteria residing in our intestines. These findings, the
results of experiments in mice and humans, were published today in Nature.
Among other things, says Dr. Eran Elinav of the Weizmann Institute's
Immunology Department, who led this research together with Prof. Eran
Segal of Computer Science and Applied Mathematics Department, the
widespread use of artificial sweeteners in drinks and food may be
contributing to the obesity and diabetes epidemic that is sweeping much
of the world.

Artificial sweeteners induce glucose intolerance by altering the gut microbiota

▶ The Immunopathogenesis of Multiple Sclerosis - YouTube

Maternal hospitalization with infection during pregnancy and risk of autism spectrum disorders

Animal models indicate that maternal infection during pregnancy can
result in behavioral abnormalities and neuropathologies in offspring. We
examined the association between maternal inpatient diagnosis with
infection during pregnancy and risk of ASD in a Swedish nationwide
register-based birth cohort born 1984-2007 with follow-up through 2011.
In total, the sample consisted of 2,371,403 persons with 24,414 ASD
cases. Infection during pregnancy was defined from ICD codes. In the
sample, 903 mothers of ASD cases (3.7%) had an inpatient diagnosis of
infection during pregnancy. Logistic regression models adjusted for a
number of covariates yielded odds ratios indicating approximately a 30%
increase in ASD risk associated with any inpatient diagnosis of
infection. Timing of infection did not appear to influence risk in the
total Swedish population, since elevated risk of ASD was associated with
infection in all trimesters. In a subsample analysis, infections were
associated with greater risk of ASD with intellectual disability than
for ASD without intellectual disability. The present study adds to the
growing body of evidence, encompassing both animal and human studies,
that supports possible immune-mediated mechanisms underlying the
etiology of ASD.

Uncovering the Hidden Risk Architecture of the Schizophrenias: Confirmation in Three Independent Genome-Wide Association Studies

The authors sought to demonstrate that schizophrenia is a
heterogeneous group of heritable disorders caused by different genotypic
networks that cause distinct clinical syndromes.

In a large genome-wide association study of cases with
schizophrenia and controls, the authors first identified sets of
interacting single-nucleotide polymorphisms (SNPs) that cluster within
particular individuals (SNP sets) regardless of clinical status. Second,
they examined the risk of schizophrenia for each SNP set and tested
replicability in two independent samples. Third, they identified
genotypic networks composed of SNP sets sharing SNPs or subjects.
Fourth, they identified sets of distinct clinical features that cluster
in particular cases (phenotypic sets or clinical syndromes) without
regard for their genetic background. Fifth, they tested whether SNP sets
were associated with distinct phenotypic sets in a replicable manner
across the three studies.

The authors identified 42 SNP sets associated with a 70% or
greater risk of schizophrenia, and confirmed 34 (81%) or more with
similar high risk of schizophrenia in two independent samples. Seventeen
networks of SNP sets did not share any SNP or subject. These disjoint
genotypic networks were associated with distinct gene products and
clinical syndromes (i.e., the schizophrenias) varying in symptoms and
severity. Associations between genotypic networks and clinical syndromes
were complex, showing multifinality and equifinality. The interactive
networks explained the risk of schizophrenia more than the average
effects of all SNPs (24%).

Schizophrenia is a group of heritable disorders caused by a
moderate number of separate genotypic networks associated with several
distinct clinical syndromes.

Metagenomic analysis of double-stranded DNA viruses in healthy adults.

The Human Microbiome Project (HMP) was undertaken with the
goal of defining microbial communities in and on the bodies of healthy
individuals using high-throughput, metagenomic sequencing analysis. The
viruses present in these microbial communities, the `human virome¿, are
an important aspect of the human microbiome that is particularly
understudied in the absence of overt disease. We analyzed eukaryotic
double-stranded DNA (dsDNA) viruses, together with dsDNA replicative
intermediates of single-stranded DNA viruses, in metagenomic sequence
data generated by the HMP. 706 samples from 102 subjects were studied,
with each subject sampled at up to five major body habitats: nose, skin,
mouth, vagina, and stool. Fifty-one individuals had samples taken at
two or three time points 30 to 359 days apart from at least one of the
body habitats.ResultsWe detected an average of 5.5 viral genera in each
individual. At least 1 virus was detected in 92% of the individuals
sampled. These viruses included herpesviruses, papillomaviruses,
polyomaviruses, adenoviruses, anelloviruses, parvoviruses, and
circoviruses. Each individual had a distinct viral profile,
demonstrating the high interpersonal diversity of the virome. Some
components of the virome were stable over time.ConclusionsThis study is
the first to use high-throughput DNA sequencing to describe the
diversity of eukaryotic dsDNA viruses in a large cohort of normal
individuals who were sampled at multiple body sites. Our results show
that the human virome is a complex component of the microbial flora.
Some viruses establish long-term infections that may be associated with
increased risk or possibly with protection from disease. A better
understanding of the composition and dynamics of the virome may hold
important keys to human health.

Increased Alzheimer's risk linked to long-term benzodiazepine use - Medical News Today

The study found that benzodiazepine use for 3 months or more was associated with an increased risk of Alzheimer's disease of up to 51%. The longer the exposure to benzodiazepines, the greater the risk of Alzheimer's. Long-acting benzodiazepines were also found to increase risk more than short-acting benzodiazepines.

Maternal complement C1q and increased odds for psychosis in adult offspring

The presence of maternal antibodies to food and infectious antigens may
confer an increased risk of developing schizophrenia and psychosis in
adult offspring. Complement factor C1q is an immune molecule with
multiple functions including clearance of antigen–antibody complexes
from circulation and mediation of synaptic pruning during fetal brain
development. To determine if maternal C1q was associated with offspring
schizophrenia and psychosis, we evaluated 55 matched case–control
maternal serum pairs from the National Collaborative Perinatal Project.
Sample pairs were composed of mothers whose offspring developed
psychoses as adults and those whose offspring were free from psychiatric
disease. Matching criteria for offspring included birth date, delivery
hospital, race, and gender, with further matching based on mother's age.
IgG markers of C1q, bovine milk casein, egg ovalbumin, and wheat gluten
were measured with enzyme-linked immunosorbent assays. C1q levels were
compared to food antigen IgG and to previously generated data for
C-reactive protein, adenovirus, herpes simplex viruses, influenza
viruses, measles virus, and Toxoplasma gondii. C1q was significantly elevated in case mothers with odds ratios of 2.66–6.31 (conditional logistic regressions, p ≤ 0.008–0.05).
In case mothers only, C1q was significantly correlated with antibodies
to both food and infectious antigens: gluten (R2 = 0.26, p ≤ 0.004), herpes simplex virus type 2 (R2 = 0.21, p ≤ 0.02), and adenovirus (R2 = 0.25, p ≤ 0.006).
In conclusion, exposure to maternal C1q activity during pregnancy may
be a risk factor for the development of schizophrenia and psychosis in
offspring. Prenatal measurement of maternal C1q may be an important and
convergent screening tool to identify potentially deleterious immune
activation from multiple sources.

Prenatal maternal immune activation causes epigenetic differences in adolescent mouse brain

Epigenetic processes such as DNA methylation have been implicated in the pathophysiology of neurodevelopmental disorders including schizophrenia and autism. Epigenetic changes can be induced by environmental exposures such as inflammation. Here we tested the hypothesis that prenatal inflammation, a recognized risk factor for schizophrenia and related neurodevelopmental conditions, alters DNA methylation in key brain regions linked to schizophrenia, namely the dopamine rich striatum and endocrine regulatory centre, the hypothalamus. DNA methylation across highly repetitive elements (long interspersed element 1 (LINE1) and intracisternal A-particles (IAPs)) were used to proxy global DNA methylation. We also investigated the Mecp2 gene because it regulates transcription of LINE1 and has a known association with neurodevelopmental disorders. Brain tissue was harvested from 6 week old offspring of mice exposed to the viral analog PolyI:C or saline on gestation day 9. We used Sequenom EpiTYPER assay to quantitatively analyze differences in DNA methylation at IAPs, LINE1 elements and the promoter region of Mecp2. In the hypothalamus, prenatal exposure to PolyI:C caused significant global DNA hypomethylation (t=2.44, P=0.019, PolyI:C mean 69.67%, saline mean 70.19%), especially in females, and significant hypomethylation of the promoter region of Mecp2, (t=3.32, P=0.002; PolyI:C mean 26.57%, saline mean 34.63%). IAP methylation was unaltered. DNA methylation in the striatum was not significantly altered. This study provides the first experimental evidence that exposure to inflammation during prenatal life is associated with epigenetic changes, including Mecp2 promoter hypomethylation. This suggests that environmental and genetic risk factors associated with neurodevelopmental disorders may act upon similar pathways. This is important because epigenetic changes are potentially modifiable and their investigation may open new avenues for treatment.

Scientists discover how to 'switch off' autoimmune diseases

Scientists have made an important breakthrough in the fight against debilitating autoimmune diseases such as multiple sclerosis by revealing how to stop cells attacking healthy body tissue. Rather than the body’s immune system destroying its own tissue by mistake, researchers at the University of Bristol have discovered how cells convert from being aggressive to actually protecting against disease.
Scientists were able to selectively target the cells that cause autoimmune disease by dampening down their aggression against the body’s own tissues while converting them into cells capable of protecting against disease. This type of conversion has been previously applied to allergies, known as ‘allergic desensitisation’, but its application to autoimmune diseases has only been appreciated recently.
The Bristol group has now revealed how the administration of fragments of the proteins that are normally the target for attack leads to correction of the autoimmune response.
Most importantly, their work reveals that effective treatment is achieved by gradually increasing the dose of antigenic fragment injected.

Here's the paper:-

Sequential transcriptional changes dictate safe and effective antigen-specific immunotherapy