Gut Microbiota from Twins Discordant for Obesity Modulate Metabolism in Mice
Establishing whether specific structural and functional configurations of a human gut microbiota are causally related to a given physiologic or disease phenotype is challenging. Twins discordant for obesity provide an opportunity to examine interrelations between obesity and its associated metabolic disorders, diet, and the gut microbiota. Transplanting the intact uncultured or cultured human fecal microbiota from each member of a discordant twin pair into separate groups of recipient germfree mice permits the donors’ communities to be replicated, differences between their properties to be identified, the impact of these differences on body composition and metabolic phenotypes to be discerned, and the effects of diet-by-microbiota interactions to be analyzed. In addition, cohousing coprophagic mice harboring transplanted microbiota from discordant pairs provides an opportunity to determine which bacterial taxa invade the gut communities of cage mates, how invasion correlates with host phenotypes, and how invasion and microbial niche are affected by human diets.
Separate groups of germfree mice were colonized with uncultured fecal microbiota from each member of four twin pairs discordant for obesity or with culture collections from an obese (Ob) or lean (Ln) co-twin. Animals were fed a mouse chow low in fat and rich in plant polysaccharides, or one of two diets reflecting the upper or lower tertiles of consumption of saturated fats and fruits and vegetables based on the U.S. National Health and Nutrition Examination Survey (NHANES). Ln or Ob mice were cohoused 5 days after colonization. Body composition changes were defined by quantitative magnetic resonance. Microbiota or microbiome structure, gene expression, and metabolism were assayed by 16S ribosomal RNA profiling, whole-community shotgun sequencing, RNA-sequencing, and mass spectrometry. Host gene expression and metabolism were also characterized.
Results and Discussion
The intact uncultured and culturable bacterial component of Ob co-twins’ fecal microbiota conveyed significantly greater increases in body mass and adiposity than those of Ln communities. Differences in body composition were correlated with differences in fermentation of short-chain fatty acids (increased in Ln), metabolism of branched-chain amino acids (increased in Ob), and microbial transformation of bile acid species (increased in Ln and correlated with down-regulation of host farnesoid X receptor signaling). Cohousing Ln and Ob mice prevented development of increased adiposity and body mass in Ob cage mates and transformed their microbiota’s metabolic profile to a leanlike state. Transformation correlated with invasion of members of Bacteroidales from Ln into Ob microbiota. Invasion and phenotypic rescue were diet-dependent and occurred with the diet representing the lower tertile of U.S. consumption of saturated fats, and upper tertile of fruits and vegetables, but not with the diet representing the upper tertile of saturated fats, and lower tertile of fruit and vegetable consumption. These results reveal that transmissible and modifiable interactions between diet and microbiota influence host biology.
Science 6 September 2013:
Vol. 341 no. 6150
The brain’s powers are a little overrated. To keep your body going, you don’t need a functioning brain, but you do need something to provide energy. Enter the gut.
Command and control
For instance, the processes the enteric nervous system performs also gives it some control over the trillions of microbes that sit in your gut. Many of them are essential for our health, because they help us extract nutrients that we wouldn’t otherwise be able to, and some even fend off infections.
And there’s more. It had been suspected that what happens in the gut could have an impact on the brain. Now we have found too many correlations to ignore the gut-to-brain connection.
Until now, however, these gut-brain connections have been mere correlations. With some help from tapeworms, a new study changes that.
Tapeworms to the rescue
One of the connecting factors between the brain and the gut has been the immune system. Neurological diseases, such as Alzheimer’s and multiple sclerosis, are linked to changes in the immune system, and auto-immune diseases of the gut, such as Crohn’s disease, are linked to mental illnesses.
She split a group of 30 rats in two: those infected with the Hymenolepis diminuta worm and those without. Then, in both groups, she induced a second infection aimed at increasing the production of a brain signaling chemical called IL-1β. The chemical is usually beneficial, but in excess it can cause damage and has been associated with brain disease.
Good gut, good brain
The reason was that mice with tapeworm infection had already had an immune response, which kept the levels of IL-1β low when a second infection came along. Lower levels of IL-1β in the brain ensured the formation and retention of memories, more than in rats without the worms. Those who hadn’t had the infection produced far greater levels of IL-1β.
Sunday, April 05, 2015
Glyphosate, Roundup, GMOs and the microbiome part 1: crowdsourcing literature
For many reasons I have been interested for the last few years in how agricultural practices affect microbiomes. For example in regard to crops, how do farming practices affect the microbiomes of the plants, the microbiomes of the soil and area around the plants, and the microbiomes of organisms (including humans) who make use of the plants?
I won’t go into all the detail right now for why I am interested in this topic but for some examples of my work in this area see The microbes we eat abundance and taxonomy of microbes consumed in a day’s worth of meals for three diet types and Structure, variation, and assembly of the root-associated microbiomes of rice.
Anyway, the reason I am writing this now is that tomorrow I am “testifying” to a NRC Committee about this topic and some related topics. The presentation will be shown live online (register here). And I thought, in the interest of openness, I would post some of what I am thinking about here before hand.
One of the key topics for tomorrow is something I have been snooping around at for a few years – how does glyphosate (the key ingredient of RoundUp and a widely used herbicide) affect microbiomes? I am interested in this from both a scientific point of view (I think it is an interesting topic) and also from a “public policy / education” point of view. I think this is a really good topic to have a public discussion of “microbiomes” and both the importance of microbial communities and the challenges with studying them. So a few years ago I started thinking about working on this and developing a “Citizen Science” project around it. And, well, I am still working on that idea and probably will be trying to launch something in the near future. As a first start I thought it would be good to start to engage the community (researchers, teachers, the public, etc) in a discussion of this topic. So .. this is the beginning of that I guess.
Some questions I think are interesting:
- Does glyphosate affect plant microbiomes?
- Does glyphosate affect soil microbiomes?
- Does consumption of plants treated with glyphosate affect the microbiomes of the consumer?
- Directly (e.g., by glyphosate itself being in the food and directly affecting microbomes”
- Indirectly (by glyphosate affecting the microbiome of the food which in turn affects the microbiome of the consumer)
- If glyphosate affects any of these microbiomes above, are these significant affects (e.g., in terms of health)?
The advancement of DNA/RNA, proteins, and metabolite analytical platforms, combined with increased computing technologies, has transformed the field of microbial community analysis. This transformation is evident by the exponential increase in the number of publications describing the composition and structure, and sometimes function, of the microbial communities inhabiting the human body. This rapid evolution of the field has been accompanied by confusion in the vocabulary used to describe different aspects of these communities and their environments. The misuse of terms such as microbiome, microbiota, metabolomic, and metagenome and metagenomics among others has contributed to misunderstanding of many study results by the scientific community and the general public alike. A few review articles have previously defined those terms, but mainly as sidebars, and no clear definitions or use cases have been published. In this editorial, we aim to propose clear definitions of each of these terms, which we would implore scientists in the field to adopt and perfect.
Americans spend the vast majority of their lives in built environments. Even traditionally outdoor pursuits, such as exercising, are often now performed indoors. Bacteria that colonize these indoor ecosystems are primarily derived from the human microbiome. The modes of human interaction with indoor surfaces and the physical conditions associated with each surface type determine the steady-state ecology of the microbial community.
Bacterial assemblages associated with different surfaces in three athletic facilities, including floors, mats, benches, free weights, and elliptical handles, were sampled every other hour (8 am to 6 pm) for 2 days. Surface and equipment type had a stronger influence on bacterial community composition than the facility in which they were housed. Surfaces that were primarily in contact with human skin exhibited highly dynamic bacterial community composition and non-random co-occurrence patterns, suggesting that different host microbiomes—shaped by selective forces—were being deposited on these surfaces through time. However, bacterial assemblages found on the floors and mats changed less over time, and species co-occurrence patterns appeared random, suggesting more neutral community assembly.
These longitudinal patterns highlight the dramatic turnover of microbial communities on surfaces in regular contact with human skin. By uncovering these longitudinal patterns, this study promotes a better understanding of microbe-human interactions within the built environment.
Bringing balance back to your gut
Cleveland Clinic asked more than 100 of its top experts about the innovations set to reshape healthcare in the coming year. These are their answers — the Top 10 Innovations for 2014.
The microbiota, or mix of microbes, in your intestines exists in a delicate state of balance. Sometimes, antibiotics used for treatment can undo that balance by killing both aggressive and friendly bacteria.
When this happens, hardy C.diff (short for Clostridium difficile) microbes live on — often with disastrous results when they spread infection from person to person. Many gastroenterologists are fighting this problem with a novel approach called fecal microbiota transplantation, a.k.a. human stool transplants.
In this therapy, doctors use a colonoscopy or enema to transfer a liquid suspension made from a healthy person’s fecal matter into a sick person’s colon. The goal is to restore bacterial balance and fight infections and diseases.
Fecal microbiota transplantation could become a primary therapy not only for C.diff infection, but also for inflammatory bowel disease.
C.diff poses such high risks because of how it spreads, particularly in hospitals. It can be transmitted to hands, food, utensils, sheets, countertops and curtains as spores. When passed to another person, these spores lead to intestinal inflammation, diarrhea, nausea, vomiting and abdominal pain. According to the U.S. Centers for Disease Control and Prevention, C. diffinfections have increased to 500,000 cases each year in the United States. That includes 15,000 deaths annually.
Fecal transplantation might help bring those numbers down.
Clinical study results have been positive. Some people who have had multiple C. diff infections have realized benefits from the therapy hours later, have been cured of their symptoms within 24 hours, and have had no further infections.
As research continues, experts expect that fecal microbiota transplantation could become a primary therapy not only for C.diff infection, but also for inflammatory bowel disease. It even holds promise for treating conditions such as rheumatoid arthritis and Parkinson’s disease.
Treating disease with fecal transplants.
One morning last fall, Jon Ritter, an architectural historian living in Greenwich Village, woke to find an e-mail from a neighbor, who had an unusual request. “Hi Jon, This is Tom Gravel, from Apt. 4N,” the e-mail began. “I wanted to check in and see if you may be open to helping me with a health condition.” Gravel, a project manager for a land-conservation group, explained that he had Crohn’s disease, an autoimmune disorder that causes inflammation of the intestinal tract along with unpredictable, often incapacitating episodes of abdominal pain and bloody diarrhea. His doctor had prescribed a succession of increasingly powerful drugs, none of which had helped. But recently Gravel had experimented with a novel therapy that, though distasteful to contemplate, seemed to relieve his symptoms: fecal transplantation, in which stool from a healthy person is transferred to the colon of someone who is sick. He hoped to enlist Ritter as a stool donor.
“I realize this is really out there,” Gravel wrote. “But I think you and your family are the nicest people in our building, and I thought I might start with lucky you.”