Serum IgG Antibody Levels to Periodontal Microbiota Are Associated with Incident Alzheimer Disease.

BACKGROUND:

Periodontitis
and Alzheimer disease (AD) are associated with systemic inflammation.
This research studied serum IgG to periodontal microbiota as possible
predictors of incident AD.

METHODS:

Using a case-cohort study design, 219 subjects (110 incident AD cases and 109
controls without incident cognitive impairment at last follow-up),
matched on race-ethnicity, were drawn from the Washington Heights-Inwood
Columbia Aging Project (WHICAP), a cohort of longitudinally followed
northern Manhattan residents aged >65 years. Mean follow-up was five
years (SD 2.6). In baseline sera, serum IgG levels were determined for
bacteria known to be positively or negatively associated with
periodontitis (Porphyromonas gingivalis, Tannerella forsythia,
Actinobacillus actinomycetemcomitans Y4, Treponema denticola,
Campylobacter rectus, Eubacterium nodatum, and Actinomyces naeslundii
genospecies-2). In all analyses, we used antibody threshold levels shown
to correlate with presence of moderate-severe periodontitis.

RESULTS:

Mean age was 72 years (SD 6.9) for controls, and 79 years (SD 4.6) for cases
(p<0.001). Non-Hispanic Whites comprised 26%, non-Hispanic Blacks
27%, and Hispanics 48% of the sample. In a model adjusting for baseline
age, sex, education, diabetes mellitus, hypertension, smoking, prior
history of stroke, and apolipoprotein E genotype, high anti-A.
naeslundii titer (>640 ng/ml, present in 10% of subjects) was
associated with increased risk of AD (HR = 2.0, 95%CI: 1.1-3.8). This
association was stronger after adjusting for other significant titers
(HR = 3.1, 95%CI: 1.5-6.4). In this model, high anti-E. nodatum IgG
(>1755 ng/ml; 19% of subjects) was associated with lower risk of AD
(HR = 0.5, 95%CI: 0.2-0.9).

CONCLUSIONS:

Serum IgG levels to common periodontal microbiota are associated with risk for developing incident AD.

Scientists identify new and beneficial function of endogenous retroviruses in immune response

Retroviruses are able to insert into the genomic DNA of cells they
infect, including germ cells. In this way, and by a process called
retrotransposition, they have become a major part of the genome of each
person. About 45 percent of a person's DNA is of retroviral origin, and
some of the better preserved copies are termed "endogenous retroviruses"
(ERV).

Writing in the journal Science, the researchers found that
when B cells are activated by large polymeric antigens such as
polysaccharides of bacteria, they rapidly produce protective antibodies
in what is termed the Type II T-independent antibody response. This
response, central to the body's defense against common bacterial and viral pathogens, is dependent on ERV.


Within activated B cells, the ERV are driven to express RNA copies of
themselves, which in turn are copied into DNA by an enzyme called
reverse transcriptase. The RNA copies of ERV are detected by a protein
called RIG-I, and the DNA copies are detected by another protein called
cGAS. These two proteins send further signals that enable the B cells to
sustain their activated state, proliferate, and produce antibodies.

Fine particulate air pollution linked with increased autism risk

Women exposed to high levels of fine particulate matter specifically
during pregnancy—particularly during the third trimester—may face up to
twice the risk of having a child with autism than mothers living in
areas with low particulate matter, according to a new study from Harvard
School of Public Health (HSPH). The greater the exposure, the greater
the risk, researchers found. It was the first U.S.-wide study exploring
the link between airborne particulate matter and autism.

Study Hints Gut Microbiome Plays A Role in Multiple Sclerosis

The investigators found that the average abundance of Methanobrevibacter was seven times greater in patients with MS than in the control group, but not every MS patient had the bacteria. Methanobrevibacter has been increasingly linked to multiple inflammatory states, but its ability to drive immune responses is not well understood, according to Dr. Jangi.

“Methanobrevibacter also live in the healthy gut, but they seem to be increased in MS patients,” he said. “Is that because in MS, the gut is not working that well that it lets the Methanobrevibacter grow more readily or is the bug somehow associated with causing the disease? It is a chicken-and-egg problem.”

The investigators also found that the average abundance of Butyricimonas was three times lower in untreated patients with MS than in healthy controls. But the levels of Butyricimonas in treated patients and healthy controls did not differ significantly, suggesting that treatment has an effect on this bacteria.

The possible role of Butyricimonas in the immune system is better understood. When Butyricimonas digests dietary fiber, butyrate is produced. Butyrate influences the production of regulatory T cells in the gut (Nature 2013;504:446-450). Previous studies have shown that patients with autoimmune conditions such as type 1 diabetes and inflammatory bowel disease have lower levels of butyrate-producing bacteria (Rev Diabet Stud 2012;9:251-259; Nestle Nutr Inst Workshop Ser 2014;79:29-39). “Butyrate probably helps to dampen the immune response,” Dr. Jangi said.

Identification of hot spots of DNA methylation in the adult male adrenal in response to in utero exposure to the ubiquitous endocrine disruptor plasticizer di-(2-ethylhexyl) phthalate.

Exposure to environmental toxicants during fetal development alters gene
expression and promotes disease later in life. Di-(2-ethylhexyl)
phthalate (DEHP) is a plasticizer widely used for the manufacturing of
consumer products. Exposure to DEHP has been associated with obesity,
asthma, and low testosterone levels. In utero exposure of pregnant dams
to DEHP from gestational day 14 until birth resulted in reduced levels
of serum testosterone and aldosterone in the adult male offspring. Since
DEHP is rapidly cleared from the body, the effects observed in the
adult are likely epigenetic in origin. Under the same experimental
conditions, we used reduced-representation bisulfite sequencing to
assess changes in DNA methylation. We identified hot spots of DNA
methylation changes primarily within CpG islands followed by shelf
regions of the genome known to control regional gene expression. We also
identified epigenomic areas responsive to exposure to environmental
levels of DEHP and found the chromosomal region that houses genes
controlling immune responsiveness to be a primary target of DEHP. These
data suggest that DEHP phthalate exposure early in life induces
epigenetic changes that may be linked to altered gene expression and
function in the adult.

Brain inflammation a hallmark of autism, large-scale analysis shows

While many different combinations of genetic traits can cause autism,
brains affected by autism share a pattern of ramped-up immune responses,
an analysis of data from autopsied human brains reveals. The study, a
collaborative effort between Johns Hopkins and the University of Alabama
at Birmingham, included data from 72 autism and control brains. It will
be published online Dec. 10 in the journal Nature Communications.

Neuroprotective kynurenine metabolite indices are abnormally reduced and positively associated with hippocampal and amygdalar volume in bipolar disorder.

Inflammation-related changes in the concentrations of kynurenine-pathway
metabolites occur in depression secondary to medical conditions but
have not been well characterized in primary bipolar disorder (BD), with
contradictory results potentially attributable to the presence or
absence of psychosis and/or medication effects. In contrast, reductions
in hippocampal and amygdalar volume that theoretically reflect dendritic
atrophy occurring in the context of a neurotoxic process are commonly
reported in unmedicated BD patients. Here we tested whether the
concentrations of putatively neuroprotective (kynurenic acid, KynA) and neurotoxic (3-hydroxy-kynurenine, 3HK and quinolinic acid,
QA) kynurenine-pathway metabolites were altered in primary BD and
whether these metabolites were associated with hippocampal and amygdalar
volume. Twenty-five moderately-to-severely depressed unmedicated
subjects and 38 moderately-to-severely depressed medicated subjects who
met DSM-IV-TR criteria for BD, as well as 48 healthy controls (HCs)
completed a structural MRI scan and provided a blood sample for
kynurenine metabolite analysis, performed using high performance liquid
chromatography with tandem mass spectrometry. Gray matter volumes were
measured with the automated segmentation software, FreeSurfer. A
putative neuroprotective index, KynA/QA, was significantly lower in the
BD subjects relative to the HCs, a finding that was unrelated to current
treatment with medication or a prior history of psychosis. Further,
another putative neuroprotective index, KynA/3HK was positively
associated with hippocampal volume in the BD group after controlling for
age, sex, body mass index (BMI), and intracranial volume (ICV). Kyn/3HK
was significantly associated with total amygdalar volume in the BD
group, but after controlling for age, sex, BMI, but not ICV, this
association was reduced to a trend. In addition, Kyn/3HK was positively
associated with amygdalar volume in the HCs although the association was
no longer significant after accounting for the effects of age, sex, and
BMI. The results raise the possibility that BD-associated abnormalities
in kynurenine metabolism may impact the structure of the hippocampus
and amygdala, highlighting a pathway through which inflammation may
exert neuropathological effects in the context of depression.

Future management of human obesity: understanding the meaning of genetic susceptibility

Gene–environment interactions are central to the expression of obesity. The condition is strongly heritable (ie, genetic), and most of the variation in obesity levels between countries and between individuals can be explained by the effects of obesogenic environments on individual genetic susceptibilities. The nature of the obesogenic environmental influences is not clear in detail, but they correlate closely with measures of affluence. The causes of variation in genetic susceptibility are also not clearly defined, but their general nature has become clearer. The failure of genome-wide association studies or large linkage studies to identify or replicate causative genetic variants, together with the segregation of obesity-related traits in families, implicates a heterogenetic mechanism in which rare, dominantly or additively expressed genetic variants are responsible for most of common obesity. The search for rare causative variants continues with some successes, but those identified contribute very little to the overall burden and, assuming heterogenetics, there are many more to find. The time when genomic risk factors provide more information than do currently available markers, such as family history, is a long way off. Genomic studies to date have contributed little, if anything, to the prevention and treatment of common obesity and its associated disorders. This contrasts with the obvious and immediate potential implications of the well-established overall genetic basis of obesity, which have not yet been exploited in the clinical or public health arenas. Genomic studies, which have helped to define the genetic basis of common obesity mainly by exclusion, will in the future play an increasingly important role in understanding and managing obesity, but only with parallel studies of the physiological, behavioral, and economic influences.

Sex-specific enhanced behavioral toxicity induced by maternal exposure to a mixture of low dose endocrine-disrupting chemicals.

Humans are increasingly and consistently exposed to a variety of
endocrine disrupting chemicals (EDCs), chemicals that have been linked
to neurobehavioral disorders such as ADHD and autism.
Many of such EDCs have been shown to adversely influence brain
mesocorticolimbic systems raising the potential for cumulative toxicity.
As such, understanding the effects of developmental exposure to
mixtures of EDCs is critical to public health protection. Consequently,
this study compared the effects of a mixture of four EDCs to their
effects alone to examine potential for enhanced toxicity, using
behavioral domains and paradigms known to be mediated by
mesocorticolimbic circuits (fixed interval (FI) schedule controlled
behavior, novel object recognition memory and locomotor activity) in
offspring of pregnant mice that had been exposed to vehicle or
relatively low doses of four EDCs, atrazine (ATR - 10mg/kg),
perfluorooctanoic acid (PFOA - 0.1mg/kg), bisphenol-A (BPA - 50μg/kg),
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD - 0.25μg/kg) alone or combined
in a mixture (MIX), from gestational day 7 until weaning. EDC-treated
males maintained significantly higher horizontal activity levels across
three testing sessions, indicative of delayed habituation, whereas no
effects were found in females. Statistically significant effects of MIX
were seen in males, but not females, in the form of increased FI
response rates, in contrast to reductions in response rate with ATR, BPA
and TCDD, and reduced short term memory in the novel object recognition
paradigm. MIX also reversed the typically lower neophobia levels of
males compared to females. With respect to individual EDCs, TCDD
produced notable increases in FI response rates in females, and PFOA
significantly increased ambulatory locomotor activity in males.
Collectively, these findings show the potential for enhanced behavioral
effects of EDC mixtures in males and underscore the need for animal
studies to fully investigate mixtures, including chemicals that converge
on common physiological substrates to examine potential mechanisms of
toxicity with full dose effect curves to assist in interpretations of
relevant mechanisms.

Surprising new leads uncovered in global obesity epidemic - News and Events - University of Sydney

Researchers have uncovered surprising new leads in the worldwide obesity epidemic by examining the combination of our rapidly changing environment with our overwhelming appetite for protein.
Published in the British Journal of Nutrition, the research from the University of Sydney's Charles Perkins Centre indicates that bottle-feeding, climate change and corporate bottom lines could be among the dark horses of global obesity.
The new leads were uncovered by comparing what is known as the Protein Leverage Hypothesis against our changing environment. The Protein Leverage Hypothesis, developed by Charles Perkins Centre researchers as part of a major breakthrough in nutrition research, identifies our overwhelming appetite for protein as the driving force behind appetite in humans and numerous other animals
Increased atmospheric carbon dioxide, an explosion in ultra-processed foods, and high-protein diets in early life, for example through baby formula instead of breast milk, could all play a role in the world's expanding waistline.

Chemicals released during natural gas extraction may harm reproduction, development -- ScienceDaily

Unconventional oil and gas (UOG) operations combine directional drilling
and hydraulic fracturing, or "fracking," to release natural gas from
underground rock. Recent discussions have centered on potential air and
water pollution from chemicals used in these processes and how it
affects the more than 15 million Americans living within one mile of UOG
operations. Now, Susan C. Nagel, a researcher with the University of
Missouri, and national colleagues have conducted the largest review to
date of research centered on fracking byproducts and their effects on
human reproductive and developmental health. They determined that
exposure to chemicals released in fracturing may be harmful to human
health in men, women and children and recommend further scientific
study.

Developmental and reproductive effects of chemicals associated with unconventional oil and natural gas operations

Unconventional oil and gas (UOG) operations have the potential to increase air and water pollution in communities located near UOG operations. Every stage of UOG operation from well construction to extraction, operations, transportation, and distribution can lead to air and water contamination. Hundreds of chemicals are associated with the process of unconventional oil and natural gas production. In this work, we review the scientific literature providing evidence that adult and early life exposure to chemicals associated with UOG operations can result in adverse reproductive health and developmental effects in humans. Volatile organic compounds (VOCs) [including benzene, toluene, ethyl benzene, and xylene (BTEX) and formaldehyde] and heavy metals (including arsenic, cadmium and lead) are just a few of the known contributors to reduced air and water quality that pose a threat to human developmental and reproductive health. The developing fetus is particularly sensitive to environmental factors, which include air and water pollution. Research shows that there are critical windows of vulnerability during prenatal and early postnatal development, during which chemical exposures can cause potentially permanent damage to the growing embryo and fetus. Many of the air and water pollutants found near UOG operation sites are recognized as being developmental and reproductive toxicants; therefore there is a compelling need to increase our knowledge of the potential health consequences for adults, infants, and children from these chemicals through rapid and thorough health research investigation.

Chemo effect on brain cells pinpointed; potential link to autism -- ScienceDaily

UNC School of Medicine researchers have found for the first time a
biochemical mechanism that could be a cause of "chemo brain" -- the
neurological side effects such as memory loss, confusion, difficulty
thinking, and trouble concentrating that many cancer patients experience
while on chemotherapy to treat tumors in other parts of the body.The research, published in the Proceedings of the National Academy of Sciences,
shows how the common chemotherapy drug topotecan can drastically
suppress the expression of Topoisomerase-1, a gene that triggers the
creation of proteins essential for normal brain function. Specifically,
the drug tamps down the proteins that are necessary for neurons to
communicate through synapses. However, the researchers found that the
protein levels and synaptic communication return to normal when the drug
is removed.

EHFPI: a database and analysis resource of essential host factors for pathogenic infection.

High-throughput screening and computational technology has greatly
changed the face of microbiology in better understanding pathogen-host
interactions. Genome-wide RNA interference (RNAi) screens have given
rise to a new class of host genes designated as Essential Host Factors
(EHFs), whose knockdown effects significantly influence pathogenic
infections. Therefore, we present the first release of a
manually-curated bioinformatics database and analysis resource EHFPI
(Essential Host Factors for Pathogenic Infection,). EHFPI captures detailed article,
screen, pathogen and phenotype annotation information for a total of
4634 EHF genes of 25 clinically important pathogenic species. Notably,
EHFPI also provides six powerful and data-integrative analysis tools,
i.e. EHF Overlap Analysis, EHF-pathogen Network Analysis, Gene
Enrichment Analysis, Pathogen Interacting Proteins (PIPs) Analysis, Drug
Target Analysis and GWAS Candidate Gene Analysis, which advance the
comprehensive understanding of the biological roles of EHF genes, as in
diverse perspectives of protein-protein interaction network, drug
targets and diseases/traits. The EHFPI web interface provides
appropriate tools that allow efficient query of EHF data and
visualization of custom-made analysis results. EHFPI data and tools
shall keep available without charge and serve the microbiology,
biomedicine and pharmaceutics research communities, to finally
facilitate the development of diagnostics, prophylactics and
therapeutics for human pathogens.

Depressive-like behavior likely exacerbated by high-fructose diet in adolescence - Medical News Today

Depressive-like behavior likely exacerbated by high-fructose diet in adolescence - Medical News Today

Prediction and quantification of bioactive microbiota metabolites in the mouse gut :

Metabolites produced by the intestinal microbiota are potentially important physiological modulators. Here we present a metabolomics strategy that models microbiota metabolism as a reaction network and utilizes pathway analysis to facilitate identification and characterization of microbiota metabolites. Of the 2,409 reactions in the model, ~53% do not occur in the host, and thus represent functions dependent on the microbiota. The largest group of such reactions involves amino-acid metabolism. Focusing on aromatic amino acids, we predict metabolic products that can be derived from these sources, while discriminating between microbiota- and host-dependent derivatives. We confirm the presence of 26 out of 49 predicted metabolites, and quantify their levels in the caecum of control and germ-free mice using two independent mass spectrometry methods. We further investigate the bioactivity of the confirmed metabolites, and identify two microbiota-generated metabolites (​5-hydroxy-L-tryptophan and ​salicylate) as activators of the ​aryl hydrocarbon receptor.

Taking antibiotics during pregnancy increases risk for child becoming obese -- ScienceDaily

A study just released by Columbia University's Mailman School of Public
Health found that children who were exposed to antibiotics in the second
or third trimester of pregnancy had a higher risk of childhood obesity
at age 7. The research also showed that for mothers who delivered their
babies by a cesarean section, whether elective or non-elective, there
was a higher risk for obesity in their offspring.

The gut microbiota influences blood-brain barrier permeability in mice

Pivotal to brain development and function is an intact blood-brain barrier (BBB), which acts as a gatekeeper to control the passage and exchange of molecules and nutrients between the circulatory system and the brain parenchyma. The BBB also ensures homeostasis of the central nervous system (CNS). We report that germ-free mice, beginning with intrauterine life, displayed increased BBB permeability compared to pathogen-free mice with a normal gut flora. The increased BBB permeability was maintained in germ-free mice after birth and during adulthood and was associated with reduced expression of the tight junction proteins occludin and claudin-5, which are known to regulate barrier function in endothelial tissues. Exposure of germ-free adult mice to a pathogen-free gut microbiota decreased BBB permeability and up-regulated the expression of tight junction proteins. Our results suggest that gut microbiota–BBB communication is initiated during gestation and propagated throughout life.

Triclosan, a common antimicrobial in personal hygiene products, causes liver fibrosis and cancer in mice

Triclosan is an antimicrobial commonly found in soaps, shampoos,
toothpastes and many other household items. Despite its widespread use,
researchers at University of California, San Diego School of Medicine
report potentially serious consequences of long-term exposure to the
chemical. The study, published Nov. 17 by Proceedings of the National Academy of Sciences,
shows that triclosan causes liver fibrosis and cancer in laboratory
mice through molecular mechanisms that are also relevant in humans.

Reconceptualizing major depressive disorder as an infectious disease

In this article, I argue for a reconceptualization of major depressive disorder (major
depression) as an infectious disease. I suggest that major depression may result from
a parasitic, bacterial, or viral infection and present examples that illustrate possible
pathways by which these microorganisms could contribute to the etiology of major depression.
I also argue that the reconceptualization of the human body as an ecosystem for these
microorganisms and the human genome as a host for non-human exogenous sequences may
greatly amplify the opportunity to discover genetic links to the illness. Deliberately
speculative, this article is intended to stimulate novel research approaches and expand
the circle of researchers taking aim at this vexing illne

Researchers discover type of toxic flame retardant in Americans for first time - Medical News Today


By analyzing phosphate biomarkers in the participants' urine - known as dialkyl or diaryl phosphates (DAPs) - the team was able to identify the presence of phosphates in their body. A previous study showed how these DAPs are present in household dust, leading the researchers to investigate whether they are present in urine.
Results of the analysis revealed that all participants had traces of one or more of the following phosphates in their urine: bis-(1,3-dichloro-2-propyl) phosphate (BDCIPP), tris-(1,3-dichloro-isopropyl) phosphate (TDCIPP) and bis-(2-chloroethyl) phosphate (BCEP). All of these are deemed harmful to human health.
"We found that several toxic flame retardants are in people's bodies. When you sit on your couch, you want to relax, not get exposed to chemicals that may cause cancer," says Dodson.
The researchers say they were surprised to find that almost all participants had traces of TDCIPP in their urine, considering that it had stopped being used in children's pajamas in the 1970s due to the potential harm it may pose to human health.