In recent years, it has become increasingly clear that many diseases are triggered or maintained by changes in bacterial communities in the gut. However, the general view up into now has been rather simple: bacteria stimulate the immune system, leading to inflammation or autoimmune disorders in a single direction.
Now, in work published in Immunity, scientists led by Sidonia Fagarasan from the RIKEN Center for Integrative Medical Science in Japan have painted a more complex picture: the gut immune system does not simply prevent the influx of pathogens, but is actively involved in the maintenance of a rich and healthy community of gut bacteria. They propose that faults in the immune regulation lead to changes in the bacterial community that in turn feed back into the immune system.
In the study, the group demonstrated that the regulation by immune T cells of immunoglobulin A (IgA), an antibody that plays a key role in immunity in the gut, is critical for the maintenance of rich bacterial communities in mammal guts.
They began by studying mice with various immune deficiencies and attempted to restore the mice by providing the missing components. They monitored the bacterial communities in the mice’s guts with or without the reconstitutions and evaluated the flow of information between the immune system and bacteria. They discovered that the precise control of IgA production by regulatory T cells is critical for keeping a rich and balanced bacterial community.
To investigate how bacteria feed back to the host, they looked at germ-free mice (mice born and maintained sterile in special incubators) and young pups that had been transplanted with different bacterial communities (either by injection of bacteria or by painting the fur with fecal bacteria extracts from normal or immune-deficient mice). They discovered that the immune system “sees” and responds differently to different bacterial communities. Rich and balanced bacterial communities seem to be perceived as “self” and induce a quick maturation of the immune system and gut responses (induction of regulatory T cells and IgA), while a poor and unbalanced bacterial community is apparently perceived as “non-self” and induces responses aimed at eliminating it (T cells with inflammatory properties and IgG or IgE responses).
According to Sidonia Fagarasan, who led the work, “This study should have an impact on the way we understand immune-related disorders associated with bacteria dysbiosis in the gut. In order to reestablish a healthy state we need to interfere not only with the bacteria, by providing probiotics or through fecal transplantation, but also with the immune system, by correcting the faults caused either by inherited deficiencies or by aging.”
“It was surprising,” she continues, “to see how the reconstitution of T cell-deficient mice with a special regulatory T cell type leads to dramatic changes in gut bacterial communities. It was spectacular to see how the immune system perceives and reacts to different bacteria communities. It gives us hopes that with a better knowledge of the symbiotic relationships between the immune system and bacteria in the gut, we could intervene and induce modifications aiming to reestablish balance and restore health.”
While many bacteria exist as aggressive pathogens, causing diseases ranging from tuberculosis and cholera, to plague, diphtheria and toxic shock syndrome, others play a less malevolent role and some are critical for human health.
In a new study, Cheryl Nickerson and her group at ASU’s Biodesign Institute, in collaboration with an international team including Tom Van de Wiele and lead author Rosemarie De Weirdt at Ghent University, Belgium, explore the role of Lactobaccilus reuteri — a natural resident of the human gut — to protect against foodborne infection.
Their results demonstrate that this beneficial or probiotic organism, which produces an antimicrobial substance known as reuterin, may protect intestinal epithelial cells from infection by the foodborne bacterial pathogen Salmonella….
A swarm of some hundred trillion bacteria occupies the human body, outnumbering human cells by about 10 to 1. Among these are members of the genus Lactobacilli, some of which have been associated with therapeutic, probiotic properties, including anti-inflammatory and anti-cancer activity.
The current study zeros in on Lactobacillus reuteri — one of the more than 180 species of Lactobacilli. The group investigated the potential of this bacterium to inhibit the early stages ofSalmonella infection, seeking to identify plausible mechanisms for such inhibitory effects.
Intestinal infections by non-typhoidal Salmonella strains induce diarrhea and gastroenteritis, and remain a leading source of foodborne illness worldwide. Such infections are acutely unpleasant but self-limiting in healthy individuals. For those with compromised immunity however, they can be deadly and the alarming incidence of multi-drug resistant Salmonellastrains has underlined the necessity of more effective therapeutics.
The use of benign microorganisms offers a promising new approach to treating infection from pathogens like Salmonellaand indeed, L. reuteri has been shown to help protect against gastrointestinal infection and reduce diarrhea in children.
The origin of L. reuteri’s protective role still remains unclear, and the present study investigated whether reuterin, a metabolite produced by L. reuteri during the process of reducing glycerol in the gut, could be one of the keys to protection. While it has been speculated that reuterin acts by regulating immune responses or competing with Salmonella for key binding sites, the current study represents the first in vitro examination of host-pathogen interactions using human intestinal epithelium in the presence of reuterin-producing L. reuteri.
- Probiotics (slideshare.net)
- Genome Project for Food Pathogens Launched by FDA (bespacific.com)
- Tummy Troubles, Colic, and Mama’s Diet (scienceofmom.com)
- FDA plans database for identifying foodborne germs (sfgate.com)
- Genome Project for Food Pathogens Launched (fda.gov)
- Toward an alternative for antibiotics to fight bacterial infections? (eurekalert.org)
- Seeking An Alternative For Antibiotics To Fight Bacterial Infections (medicalnewstoday.com)
- The Surprising Viruses in Our Gut [The Weizmann Wave] (scienceblogs.com)
Somehow I always felt this to be true…
Many scientists now regard human bodies as “supra-organisms”, collections of communities made up of human and microbial cells coexisting in a whole that is more than the sum of its parts.
Scientists working on a huge project that has mapped all the different microbes that live in and on a healthy human body have made a number of remarkable discoveries, including the fact that harmful bacteria can live in healthy bodies and co-exist with their host and other microbes without causing disease.
This week sees the publication of several papers from the Human Microbiome Project (HMP), including two in Nature and two inPLoS ONE.
The microbiome is the sum of all the microbes that colonize the body: it comprises trillions of microorganisms that outnumber human cells by 10 to 1. The microbes inhabit every nook and cranny of the body, and most of the time the relationship is a friendly one, because they help digest food, strengthen the immune system and fight off dangerous pathogens.
Colorado University (CU)-Boulder Associate Professor Rob Knight of the BioFrontiers Institute is co-author on the two Nature papers. He told the press that the microbiome may only make up 1 to 3% of human body mass, but it plays a key role in human health.
One of the fascinating features of the microbiome is that different body sites have different communites of microorganisms that are as different from each other as the differences between microbial communities in oceans and deserts.
“By better understanding this microbial variation we can begin searching for genetic biomarkers for disease.”
Another of the curious features the HMP has discovered is that even healthy people carry low levels of harmful bacteria, but as long as the body remains healthy, they don’t cause disease, they just coexist alongside beneficial microbes. …
The HMP researchers established that more than 10,000 microbial species inhabit the human “ecosystem”. Knight said they believe they have now found between 81 and 99% of all genera of microorganisms in healthy adult Americans.
One of the key findings was the stark differences in microbial communities across the human body. For instance, the microbial communities that live on the teeth are different from those in saliva. …
…Another interesting discovery is that of the genes that influence human metabolism, most of them are in the microbiome and not in the human genome…
…gut bacteria do more than break down food and its constituents like proteins, fats and carbohydrates, they also produce beneficial compounds like vitamins and anti-inflammatories.
- Human Microbiome Project Decodes Our 100 Trillion Good Bacteria (nytimes.com)
- Microbe census maps out human body’s viruses, amoebas, other bugs – Los Angeles Times (latimes.com)
- NIH Human Microbiome Project defines normal bacterial makeup of the body (eurekalert.org)
- 10,000 germ species live in and on healthy people (kansascity.com)
- Man’s microbes help map ‘normal’ in humans (vitals.msnbc.msn.com)
- Human Microbiome Project outlines powerful new methods for cataloging and analyzing microbes (eurekalert.org)
- Normal bacterial makeup has huge implications for health, says CU professor (eurekalert.org)
- Did you know… Your cooties could keep you healthy?! (warmsouthernbreeze.wordpress.com)
- Scientists map bacteria living inside us (cbc.ca)
- 10,000 germ species live in and on healthy people (newsobserver.com)
- 10,000 germ species live in and on healthy people (stuff.co.nz)
- More than 1 way to be healthy: Map of bacterial makeup of humans reveals microbial rare biosphere (eurekalert.org)
- Census of microbes in healthy humans reported (eurekalert.org)
- Gut Microbiota Transplantation May Prevent Development Of Diabetes And Fatty Liver Disease (jflahiff.wordpress.com)
- Finally, A Map Of All The Microbes On Your Body (npr.org)
- 10,000 germ species live in and on healthy people (foxnews.com)
- NIH Human Microbiome Project defines normal bacterial makeup of the body (nih.gov)
The billions of bugs in our guts have a newfound role: regulating the immune system and related autoimmune diseases such as rheumatoid arthritis, according to researchers at Mayo Clinic and the University of Illinois at Urbana-Champaign.
Larger-than-normal populations of specific gut bacteria may trigger the development of diseases like rheumatoid arthritis and possibly fuel disease progression in people genetically predisposed to this crippling and confounding condition, say the researchers, who are participating in the Mayo Illinois Alliance for Technology Based Healthcare.
The study is published in the April 2012 issue of PLoS ONE.
“A lot of people suspected that gut flora played a role in rheumatoid arthritis, but no one had been able to prove it because they couldn’t say which came first — the bacteria or the genes,” says senior author Veena Taneja, Ph.D., a Mayo Clinic immunologist. “Using genomic sequencing technologies, we have been able to show the gut microbiome may be used as a biomarker for predisposition.”…
…Researchers found that hormones and changes related to aging may further modulate the gut immune system and exacerbate inflammatory conditions in genetically susceptible individuals…
“The gut is the largest immune organ in the body,” says co-author Bryan White, Ph.D., director of the University of Illinois’ Microbiome Program in the Division of Biomedical Sciences and a member of the Institute for Genomic Biology. “Because it’s presented with multiple insults daily through the introduction of new bacteria, food sources and foreign antigens, the gut is continually teasing out what’s good and bad.”
The gut has several ways to do this, including the mucosal barrier that prevents organisms — even commensal or “good” bacteria — from crossing the lumen of the gut into the human body. However, when commensal bacteria breach this barrier, they can trigger autoimmune responses. The body recognizes them as out of place, and in some way this triggers the body to attack itself, he says….
- Sick from your stomach: Bacterial changes may trigger diseases like rheumatoid arthritis (eurekalert.org)
More research needed, still these scientists may be on to a contributing factor in weight control…
Microorganisms in the human gastrointestinal tract form an intricate, living fabric made up of some 500 to 1000 distinct bacterial species, (in addition to other microbes). Recently, researchers have begun to untangle the subtle role these diverse life forms play in maintaining health and regulating weight….
Research conducted by the authors and others has demonstrated that hydrogen-consuming methanogens appear in greater abundance in obese as opposed to normal weight individuals. Further, the Firmicutes — a form of acetogen — also seem to be linked with obesity. Following fermentation, SCFAs persist in the colon. Greater concentration of SCFAs, especially propionate, were observed in fecal samples from obese as opposed to normal weight children. (SCFAs also behave as signaling molecules, triggering the expression of leptin, which acts as an appetite suppressor.)
While it now seems clear that certain microbial populations help the body process otherwise indigestible carbohydrates and proteins, leading to greater energy extraction and associated weight gain, experimental results have shown some inconsistency. For example, while a number of studies have indicated a greater prevalence of Bacteroidetes in lean individuals and have linked the prevalence of Firmicutes with obesity, the authors stress that many questions remain.
Alterations in gut microbiota are also of crucial concern for the one billion people worldwide who suffer from undernutrition. Illnesses resulting from undernutrition contribute to over half of the global fatalities in children under age 5. Those who do survive undernutrition often experience a range of serious, long-term mental and physical effects. The role of gut microbial diversity among the undernourished has yet to receive the kind of concentrated research effort applied to obesity — a disease which has reached epidemic proportions in the developed world.
Exploiting microbes affecting energy extraction may prove a useful tool for non-surgically addressing obesity as well as treating undernutrition, though more research is needed for a full understanding of regulatory mechanisms governing the delicate interplay between intestinal microbes and their human hosts….
- Complex world of microbes fine-tune body weight (medicalxpress.com)
- We are not alone: How the bugs in our gut influence our eating habbits (thebrainbank.scienceblog.com)
- Complex world of microbes fine-tune body weight (eurekalert.org)
- Gut Bacteria Determine How Fat You’ll Be (news.softpedia.com)
- Good bugs gone bad: Gut immune cells keep beneficial microbes in their place (medicalxpress.com)
- Microbes and Weight: Do Gut Bacteria Influence How We Eat? (organicauthority.com)
- Gut Microbiota Transplantation May Prevent Development Of Diabetes And Fatty Liver Disease (jflahiff.wordpress.com)
- Gut Check: Future of Drugs May Rest with Your Microbes (livescience.com)
- Microbes Control your Immune Response – and Maybe Your Weight too, From Harvard’s The Truth About Your Immune System Special Health Report (prweb.com)
- Breast-fed babies’ gut microbes contribute to healthy immune systems (eurekalert.org)