Thursday, October 20, 2016

Visceral Fat Not Only An Alien Invader, It's a HERITABLE Alien Invader!!!

biomedcentral |  Variation in the human fecal microbiota has previously been associated with body mass index (BMI). Although obesity is a global health burden, the accumulation of abdominal visceral fat is the specific cardio-metabolic disease risk factor. Here, we explore links between the fecal microbiota and abdominal adiposity using body composition as measured by dual-energy X-ray absorptiometry in a large sample of twins from the TwinsUK cohort, comparing fecal 16S rRNA diversity profiles with six adiposity measures.

We profile six adiposity measures in 3666 twins and estimate their heritability, finding novel evidence for strong genetic effects underlying visceral fat and android/gynoid ratio. We confirm the association of lower diversity of the fecal microbiome with obesity and adiposity measures, and then compare the association between fecal microbial composition and the adiposity phenotypes in a discovery subsample of twins. We identify associations between the relative abundances of fecal microbial operational taxonomic units (OTUs) and abdominal adiposity measures. Most of these results involve visceral fat associations, with the strongest associations between visceral fat and Oscillospira members. Using BMI as a surrogate phenotype, we pursue replication in independent samples from three population-based cohorts including American Gut, Flemish Gut Flora Project and the extended TwinsUK cohort. Meta-analyses across the replication samples indicate that 8 OTUs replicate at a stringent threshold across all cohorts, while 49 OTUs achieve nominal significance in at least one replication sample. Heritability analysis of the adiposity-associated microbial OTUs prompted us to assess host genetic-microbe interactions at obesity-associated human candidate loci. We observe significant associations of adiposity-OTU abundances with host genetic variants in the FHIT, TDRG1 and ELAVL4 genes, suggesting a potential role for host genes to mediate the link between the fecal microbiome and obesity.
Our results provide novel insights into the role of the fecal microbiota in cardio-metabolic disease with clear potential for prevention and novel therapies.

New Study Links Protein in Wheat to the Inflammation of Chronic Health Conditions

sciencenewsline |  Scientists have discovered that a protein in wheat triggers the inflammation of chronic health conditions, such as multiple sclerosis, asthma and rheumatoid arthritis, and also contributes towards the development of non-coeliac gluten sensitivity.

With past studies commonly focusing on gluten and its impact on digestive health, this new research, presented at UEG Week 2016, turns the spotlight onto a different family of proteins found in wheat called amylase-trypsin inhibitors (ATIs). The study shows that the consumption of ATIs can lead to the development of inflammation in tissues beyond the gut, including the lymph nodes, kidneys, spleen and brain. Evidence suggests that ATIs can worsen the symptoms of rheumatoid arthritis, multiple sclerosis, asthma, lupus and non-alcoholic fatty liver disease, as well as inflammatory bowel disease.

ATIs make up no more than 4% of wheat proteins, but can trigger powerful immune reactions in the gut that can spread to other tissues in the body. Lead researcher, Professor Detlef Schuppan from the Johannes Gutenberg University, Germany, explains, "As well as contributing to the development of bowel-related inflammatory conditions, we believe that ATIs can promote inflammation of other immune-related chronic conditions outside of the bowel. The type of gut inflammation seen in non-coeliac gluten sensitivity differs from that caused by coeliac disease, and we do not believe that this is triggered by gluten proteins. Instead, we demonstrated that ATIs from wheat, that are also contaminating commercial gluten, activate specific types of immune cells in the gut and other tissues, thereby potentially worsening the symptoms of pre-existing inflammatory illnesses".

Clinical studies are now due to commence to explore the role that ATIs play on chronic health conditions in more detail. "We are hoping that this research can lead us towards being able to recommend an ATI-free diet to help treat a variety of potentially serious immunological disorders" adds Professor Schuppan.

Wednesday, October 5, 2016

Obesity genes probably didn't evolve to help us survive famine

physorg |  Genes that helped our ancestors store fat in times of famine may have been useful, but whether they cursed future generations with a predisposition toward obesity is a little more controversial. This popular "thrifty gene hypothesis" has had its critics, but with a study published September 22 in Cell Metabolism, there is now evidence that nearly all the common obesity-related genes show no properties of traits that evolved because they provide an adaptive advantage.

"This is probably the hardest evidence so far against the thrifty gene hypothesis—our ambition here is for people to entertain a wider range of ideas about where the genetic basis of complex diseases, like obesity, comes from," says John Speakman, a biologist at the Chinese Academy of Sciences Institute of Genetics and Developmental Biology in Beijing, who co-authored the piece with Guanlin Wang, one of his PhD students at the Chinese Academy of Sciences. "The process of evolution is a lot more complex than just the spread of favorable traits by natural selection, and the thrifty gene is like an emblem of this older way of thinking about evolutionary aspects of medicine."

Thursday, September 1, 2016

fungal infections acquire drug-resistance

guardian |  “Fungi are everywhere,” said Prof Gordon Brown, head of the Aberdeen mycology centre.
“We breathe in more than 100 spores of aspergillus every day. Normally our immune systems mop them up but, when our disease defences are compromised – for example, during cancer treatments or after traumatic injuries – they lose the ability to fight back. 

“Fungi can spread through patients’ bodies and into their spines and brains. Patients who would otherwise survive treatments are dying every year from such infections.”

This point was also stressed by Prof Neil Gow, another Aberdeen researcher. “Essentially fatal fungal infections are diseases of the diseased,” he said. 

In addition, premature babies and patients with the inherited condition cystic fibrosis are also vulnerable. 

However, the problem is even worse in developing countries. In sub-Saharan nations, where millions are infected with HIV – which causes severe depletion of patients’ immune systems – infections with cryptococcus and pneumocystis fungi account for more than half a million deaths a year.

“The total global number of fungal deaths is about the same as the number of deaths from malaria but the amount that is spent on fungal infection research is only a fraction of the cash that goes on malaria research,” added Gow.

A vaccine that could protect against fungal disease has yet to be developed, while the rise of resistance to the class of medicines known as azole drugs is causing alarm among doctors.

Recent reports from the US and Europe indicate that resistance to azole drugs is increasing in both aspergillus and candida fungi. The widespread use of agricultural fungicides to protect crops and their use in some paints and coatings has been linked to the rise of this resistance.

gnotobiotic: the woes of a germ-free organism

guardian |  Peering inside one of these chambers, I met the eyes of one of the strangest animals on the planet. It looked like just a mouse, and that is precisely why it was so weird. It was just a mouse, and nothing more.

Almost every other animal on Earth, whether centipede or crocodile, flatworm or flamingo, hippo or human, is a teeming mass of bacteria and other microbes. Each of these miniature communities is known as a microbiome. Every human hosts a microbiome consisting of some 39 trillion microbes, roughly one for each of their own cells. Every ant in a colony is a colony itself. Every resident in a zoo is a zoo in its own right. Even the simplest of animals such as sponges, whose static bodies are never more than a few cells thick, are home to thriving microbiomes.

But not the mice in Gordon’s lab. They spend their entire lives separated from the outside world, and from microbes. Their isolators contain everything they need: drinking water, brown nuggets of chow, straw chips for bedding, and a white styrofoam hutch for mating in privacy. Gordon’s team irradiates all of these items to sterilise them before piling them into loading cylinders. They sterilise the cylinders by steaming them at a high temperature and pressure, before hooking them to portholes in the back of the isolators, using connecting sleeves that they also sterilise.

It is laborious work, but it ensures that the mice are born into a world without microbes, and grow up without microbial contact. The term for this is “gnotobiosis”, from the Greek for “known life”. We know exactly what lives in these animals – which is nothing. Unlike every other mouse on the planet, each of these rodents is a mouse and nothing more. An empty vessel. A silhouette, unfilled. An ecosystem of one.

Each isolator had a pair of black rubber gloves affixed to two portholes, through which the researchers could manipulate what was inside. The gloves were thick. When I stuck my hands in, I quickly started sweating.

I awkwardly picked up one of the mice. It sat snugly on my palm, white-furred and pink-eyed. It was a strange feeling: I was holding this animal but only via two black protrusions into its hermetically sealed world. It was sitting on me and yet completely separated from me. When I had shaken hands with Gordon earlier, we had exchanged microbes. When I stroked this mouse, we exchanged nothing.
The mouse seemed normal, but it was not. Growing up without microbes, its gut had not developed properly – it had less surface area for absorbing nutrients, its walls were leakier, it renewed itself at a slower pace, and the blood vessels that supplied it with nutrients were sparse. The rest of its body hadn’t fared much better. Compared with its normal microbe-laden peers, its bones were weaker, its immune system was compromised, and it probably behaved differently too. It was, as microbiologist Theodor Rosebury once wrote, “a miserable creature, seeming at nearly every point to require an artificial substitute for the germs [it] lacks”.

Wednesday, July 27, 2016

leaky-gut syndrome confirmed at columbia university...,

columbia |  A new study may explain why people who do not have celiac disease or wheat allergy nevertheless experience a variety of gastrointestinal and extra-intestinal symptoms after ingesting wheat and related cereals. The findings suggest that these individuals have a weakened intestinal barrier, which leads to a body-wide inflammatory immune response.

Findings from the study, which was led by researchers from Columbia University Medical Center (CUMC), were reported in the journal Gut.

“Our study shows that the symptoms reported by individuals with this condition are not imagined, as some people have suggested,” said study co-author Peter H. Green, MD, the Phyllis and Ivan Seidenberg Professor of Medicine at CUMC and director of the Celiac Disease Center. “It demonstrates that there is a biological basis for these symptoms in a significant number of these patients.”

Celiac disease is an autoimmune disorder in which the immune system mistakenly attacks the lining of the small intestine after someone who is genetically susceptible to the disorder ingests gluten from wheat, rye, or barley. This leads to a range of gastrointestinal symptoms, including abdominal pain, diarrhea, and bloating.

Researchers have struggled to determine why some people, who lack the characteristic blood, tissue, or genetic markers of celiac disease, experience celiac-like GI symptoms, as well as certain extra-intestinal symptoms, such as fatigue, cognitive difficulties, or mood disturbance, after ingesting foods that contain wheat, rye, or barley. One explanation for this condition, known as non-celiac gluten or wheat sensitivity (NCWS), is that exposure to the offending grains somehow triggers acute systemic immune activation, rather than a strictly localized intestinal immune response. Because there are no biomarkers for NCWS, accurate figures for its prevalence are not available, but it is estimated to affect about 1 percent of the population, or 3 million Americans, roughly the same prevalence as celiac disease.

Monday, July 25, 2016

the poop gap

westhunt |  There’s a new article out in Science tracing the splits in gut flora. It looks as if the gut bacteria in chimpanzees split with those in humans 5.3 million years: doesn’t quite match our genetic estimates based on Human/chimp autosomal DNA differences, but it’s in the ball park. They estimate the human-gorilla split at 15.6 million year ago, but that can’t be right: we know that gorillas split off just a bit before the human-chimp split. Perhaps gorilla diet changed drastically, and maybe they picked up new bacteria from some other species.

Different populations of modern humans apparently have pretty different microbiomes. The gut bacteria from people in Malawi appear to have diverged 1.7 million years ago from those in Europeans (people from Connecticut). That is surely too old to be a consequence of modern humans’ trek out of Africa: it looks as if AMH, after leaving Africa, picked up gut flora from archaic sapiens like Neanderthals and Denisovans and dwarves.

Microbiomes are trendy. We know that fecal transplants can cure C difficile (pseudomembranous colitis) lickety-split: they might help with Crohn’s disease and ulcerative colitis. Some researchers think the microbiome has something to do with the initiation of multiple sclerosis. Others suspect that it may play a role regulating how people think and feel – in particular, mood disorders. Autism has been mentioned. 

So.. Poop matters: it certainly can affect health, and it may influence brain function. People from sub-Saharan have divergent poop, or you could say that Eurasians do. Are there differences in brain function between sub-Saharan Africans and Eurasians? Sure: Africans do poorly on IQ tests and in academic subjects. They have significant higher rates of schizophrenia, higher murder rates, etc.
Maybe it’s the poop. It’s worth checking out. Perhaps the fault lies not in our stars, or our genes, but in our stool. 

Already, eager experimenters – paleos on stilts – are trying to dramatically modulate their internal flora.