Immune System and Inflammation – 3 Articles

Altering the Community of Gut Bacteria Promotes Health and Increases Lifespan

Jan. 16, 2014 — Scientists at the Buck Institute for Research on Aging have promoted health and increased lifespan in Drosophila by altering the symbiotic, or commensal, relationship between bacteria and the absorptive cells lining the intestine. The research, appearing in the January 16, 2014 edition of Cell, provides a model for studying many of the dysfunctions that are characteristic of the aging gut and gives credence to the growing supposition that having the right balance of gut bacteria may be key to enjoying a long healthy life.

Even though recent research in humans has linked the composition of gut flora with diet and health in the elderly and the list of age-related diseases associated with changes in gut bacteria include cancer, diabetes, and inflammatory bowel disease, lead author and Buck faculty Heinrich Jasper, PhD, says there is no systematic understanding of how we go from having a young, healthy gut to one that is old and decrepit. “Our study explores age-related changes in the gut that include increased oxidative stress, inflammation, impaired efficiency of the immune response, and the over-proliferation of stem cells,” said Jasper. “It puts these changes into a hierarchical, causal relationship and highlights the points where we can intervene to rescue the negative results of microbial imbalance.”

Jasper says the bacterial load in fly intestines increases dramatically with age, resulting in an inflammatory condition. The imbalance is driven by chronic activation of the stress response gene FOXO (something that happens with age), which suppresses the activity of a class of molecules (PGRP-SCs, homologues of PGLYRPs in humans) that regulate the immune response to bacteria. PGRP-SC suppression deregulates signaling molecules (Rel/NFkB) that are important to mount an effective immune response to gut bacteria. The resulting immune imbalance allows bacterial numbers to expand, triggering an inflammatory response that includes the production of free radicals. Free radicals, in turn, cause over-proliferation of stem cells in the gut, resulting in epithelial dysplasia, a pre-cancerous state.

Jasper said the most exciting result of their study occurred when his group increased the expression of PGRP-SC in epithelial cells of the gut, which restored the microbial balance and limited stem cell proliferation. This enhancement of PGRP-SC function, which could be mimicked by drugs, was sufficient to increase lifespan of flies. “If we can understand how aging affects our commensal population — first in the fly and then in humans — — our data suggest that we should be able to impact health span and life span quite strongly, because it is the management of the commensal population that is critical to the health of the organism.”

Story Source:
The above story is based on materials provided by Buck Institute for Age Research.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Journal Reference:
Linlin Guo, Jason Karpac, Susan L. Tran, Heinrich Jasper. PGRP-SC2 Promotes Gut Immune Homeostasis to Limit Commensal Dysbiosis and Extend Lifespan. Cell, 2014; 156 (1-2): 109 DOI: 10.1016/j.cell.2013.12.018

 

Human Genes Influence Gut Microbial Composition, Study Suggests

Jan. 7, 2013 — New research led by the Karolinska Institutet, Sweden and the University of Glasgow, Scotland, has identified a link between a human gene and the composition of human gastrointestinal bacteria. In a study published as a letter to the journalGut, the team outline new evidence suggesting that the human genome may play a role in determining the makeup of the billions of microbes in the human gastrointestinal tract collectively known as the gut microbiota.

Mauro D’Amato, Associate Professor at the Department of Biosciences and Nutrition at Karolinska Institutet, said: “The hypothesis that our genes contribute to tailor-make our microbiota is very attractive. We still do not know whether certain DNA variations can result in the assembling and perpetuation of specific microbiota profiles, and this may bear important implications for the potential to treat common diseases through therapeutic modification of the gut flora.”

The microbiota, which evolved over tens of thousands of years alongside their human hosts, constitutes a complex and diverse community whose exact composition varies from person to person. It has numerous beneficial physiological and nutritional effects for humans; however, alterations in its bacterial composition have been linked to health problems including obesity and Crohns disease.

Dr Christopher Quince, of the University of Glasgow’s School of Engineering, said: “We ran a statistical analysis on bacterial DNA sequenced from samples of intestinal tissue from 51 healthy people with no history of bowel conditions in relation to 30 specific genes. These genes have been shown to increase the risk of Crohn’s disease, and are likely to play an important role in gut-bacteria interactions. We found that DNA variation in one of these genes, known as IRGM, was associated with the presence of increased levels of a type of microbe known as Prevotella.”

The research thus suggests that the IRGM gene could play a role in influencing the overall makeup of an individuals microbiota, pushing it towards Prevotella dominance instead of an alternative community dominated by a closely related bacteria, Bacteroides. Medical researchers are already considering therapeutic strategies to treat diseases by restoring “norma” intestinal flora in patients by using pharmacological or dietary changes to create specific modifications in the gut microbiota. Future research, expanding on the current study, could help to more effectively target these treatments.

Associate Professor D’Amato said: “Primarily a proof-of-concept investigation, our pilot study reinforces the idea that large-scale analyses should be undertaken to unravel how variation in the entire human genome relates to variation in the human microbiota.”

Dr Quince added: “This is a small study but it could have important implications. Weve provided further evidence that the human microbiome may also depend on the human genome, which invites serious investigation in the future.”

The study was conducted by an international team of scientists from Karolinska Institutet, University of Glasgow, University of Newcastle, Australia, Stockholm University, KTH Royal Institute of Technology, Sweden, and Science for Life Laboratory, Sweden. The work was funded by grants from the Swedish Research Council, AFA Insurance, the Swedish Society of Medicine, Ragnar Söderbergs Foundations, the EU FP7 consortium Tornado, and EPSRC Career Acceleration Fellowship.

From Science Daily dot com

A Galaxy Within Us: Our Gut Microbiota and How It Can Be Programmed by Food

From ScienceDaily. com Nov. 1, 2013 — Who would have thought that the human body contains over 10 times the amount of bacterial cells as human cells? These bacteria — now collectively called the gut microbiota — number in their trillions and are made up of more than a 1,000 different species most of which are beneficial in some way.

“Research is starting to show that the food we eat has a huge bearing on the composition of this collective and also that the profile of the collection of bacteria can be associated with a person’s health status,” explains Dr Paul Ross, Head of the Teagasc Food Research Programme and Principal Investigator at the Alimentary Pharmabiotic Centre, Teagasc, Food Research Centre, Moorepark.

To the team at the Alimentary Pharmabiotic Centre (APC), an SFI-funded CSET at Teagasc, Food Research Centre, Moorepark and at University College Cork, the study of the human microbiota has the potential to transform much of the thinking around basic human nutrition, gut health and disease prevention: “This has been made possible through developments made in DNA sequencing technology which has allowed the study of complex microbial communities such as the human gut microbiota, the majority of which cannot be cultured on an individual basis,” explains Dr Ross.

Although the composition of the microbiota is highly stable during adulthood, there are times when it can be highly dynamic — such as at the extremes of life, e.g., following birth, during inflammatory bowel conditions, gastrointestinal infection and in the elderly. Despite this stability, the microbiota also displays a high degree of interindividual variation reflecting differences in lifestyle, diet, host genetics, etc.

In a project called ELDERMET, a team of UCC/Teagasc scientists headed by Professor Paul O’Toole has recently profiled the faecal microbiota from elderly people in different residences including community, day-hospital, rehabilitation or long-term residential care locations.

This study found that the microbiota correlated with the residence location. “The results demonstrated that the individual microbiota of people in long-stay care was significantly less diverse than those that resided in the community,” explains Dr Ross. “In addition, these subjects were also clustered by diet by the same residence location and microbiota groupings. Interestingly, the separation of microbiota composition correlated significantly with health parameters in these individuals including measures of frailty, co-morbidity, nutritional status, markers of inflammation and with metabolites in faecal water.”

Taken together these data suggest that diet can programme the gut microbiota — the composition of which correlates with health status. Such a suggestion opens up great potential for the food industry in the design of food ingredients and supplements which may in the future shape the microbiota in a particular direction to correlate with an improved consumer health status. Interestingly, a related study called INFANTMET, funded by the Department of Agriculture, Food and the Marine and led by Professor Catherine Stanton at Teagasc Moorepark, is looking at the development of the gut microbiota in early life as a consequence of breast feeding.

And I add, thankfully, research has BEEN showing this info for quite a while and NOW it’s reaching a broader base & large industries are starting to pay heed-!

Intestinal Bacteria Linked to Rheumatoid Arthritis

From ScienceDaily. com Nov. 5, 2013 — Researchers have linked a species of intestinal bacteria known as Prevotella copri to the onset of rheumatoid arthritis, the first demonstration in humans that the chronic inflammatory joint disease may be mediated in part by specific intestinal bacteria. The new findings by laboratory scientists and clinical researchers in rheumatology at NYU School of Medicine add to the growing evidence that the trillions of microbes in our body play an important role in regulating our health.

Using sophisticated DNA analysis to compare gut bacteria from fecal samples of patients with rheumatoid arthritis and healthy individuals, the researchers found that P. copri was more abundant in patients newly diagnosed with rheumatoid arthritis than in healthy individuals or patients with chronic, treated rheumatoid arthritis. Moreover, the overgrowth of P. copri was associated with fewer beneficial gut bacteria belonging to the genera Bacteroides.

“Studies in rodent models have clearly shown that the intestinal microbiota contribute significantly to the causation of systemic autoimmune diseases,” says Dan R. Littman, MD, PhD, the Helen L. and Martin S. Kimmel Professor of Pathology and Microbiology and a Howard Hughes Medical Institute investigator.
“Our own results in mouse studies encouraged us to take a closer look at patients with rheumatoid arthritis, and we found this remarkable and surprising association,” says Dr. Littman, whose basic science laboratory at NYU School of Medicine’s Skirball Institute of Biomolecular Medicine collaborated with clinical investigators led by Steven Abramson, MD, senior vice president and vice dean for education, faculty, and academic affairs; the Frederick H. King Professor of Internal Medicine; chair of the Department of Medicine; and professor of medicine and pathology at NYU School of Medicine.

“At this stage, however, we cannot conclude that there is a causal link between the abundance of P. copri and the onset of rheumatoid arthritis,” Dr. Littman says. “We are developing new tools that will hopefully allow us to ask if this is indeed the case.”

The new findings, reported today in the open-access journal eLife, were inspired by previous research in Dr. Littman’s laboratory, collaborating with Harvard Medical School investigators, using mice genetically predisposed to rheumatoid arthritis, which resist the disease if kept in sterile environments, but show signs of joint inflammation when exposed to otherwise benign gut bacteria known as segmented filamentous bacteria.

Rheumatoid arthritis, an autoimmune disease that attacks joint tissue and causes painful, often debilitating stiffness and swelling, affects 1.3 million Americans. It strikes twice as many women as men and its cause remains unknown although genetic and environmental factors are thought to play a role.

The human gut is home to hundreds of species of beneficial bacteria, including P. copri, which ferment undigested carbohydrates to fuel the body and keep harmful bacteria in check. The immune system, primed to attack foreign microbes, possesses the extraordinary ability to distinguish benign or beneficial bacteria from pathogenic bacteria. This ability may be compromised, however, when the gut’s microbial ecosystem is thrown off balance.

“Expansion of P. copri in the intestinal microbiota exacerbates colonic inflammation in mouse models and may offer insight into the systemic autoimmune response seen in rheumatoid arthritis,” says Randy S. Longman, MD, PhD, a post-doctoral fellow in Dr. Littman’s laboratory and a gastroenterologist at Weill-Cornell, and an author on the new study. Exactly how this expansion relates to disease remains unclear even in animal models, he says.

Why P. copri growth seems to take off in newly diagnosed patients with rheumatoid arthritis is also unclear, the researchers say. Both environmental influences, such as diet and genetic factors can shift bacterial populations within the gut, which may set off a systemic autoimmune attack. Adding to the mystery, P. copri extracted from stool samples of newly diagnosed patients appears genetically distinct from P. copri found in healthy individuals, the researchers found.

To determine if particular bacterial species correlate with rheumatoid arthritis, the researchers sequenced the so-called 16S gene on 44 fecal DNA samples from newly diagnosed patients with rheumatoid arthritis prior to immune-suppressive treatment; 26 samples from patients with chronic, treated rheumatoid arthritis; 16 samples from patients with psoriatic arthritis (characterized by red, flaky skin in conjunction with joint inflammation); and 28 samples from healthy individuals.

Seventy-five percent of stool samples from patients newly diagnosed with rheumatoid arthritis carried P. copri compared to 21.4% of samples from healthy individuals; 11.5% from chronic, treated patients; and 37.5% from patients with psoriatic arthritis.

Rheumatoid arthritis is treated with an assortment of medications, including antibiotics, anti-inflammatory drugs like steroids, and immunosuppressive therapies that tame immune reactions. Little is understood about how these medications affect gut bacteria. This latest research offers an important clue, showing that treated patients with chronic rheumatoid arthritis carry smaller populations of P. copri. “It could be that certain treatments help stabilize the balance of bacteria in the gut,” says Jose U. Scher, MD, director of the Microbiome Center for Rheumatology and Autoimmunity at NYU Langone Medical Center’s Hospital for Joint Diseases, and an author on the new study. “Or it could be that certain gut bacteria favor inflammation.”

The researchers plan to validate their results in regions beyond New York, since gut flora can vary across geographical regions, and investigate whether the gut flora can be used as a biological marker to guide treatment. “We want to know if people with certain populations of gut bacteria respond better to certain treatment than others,” says Dr. Scher. Finally, they hope to study people before they develop rheumatoid arthritis to see whether overgrowth of P. copri is a cause or result of autoimmune attacks.