Obesity and diabetes in humans are associated with increased rates of anxiety and depression. To understand the role of the gut microbiome and brain insulin resistance in these disorders, we evaluated behaviors and insulin action in brain of mice with diet-induced obesity (DIO) with and without antibiotic treatment. We find that DIO mice have behaviors reflective of increased anxiety and depression. This is associated with decreased insulin signaling and increased inflammation in the nucleus accumbens and amygdala. Treatment with oral metronidazole or vancomycin decreases inflammation, improves insulin signaling in the brain and reduces signs of anxiety and depression. These effects are associated with changes in the levels of tryptophan, GABA, BDNF, amino acids, and multiple acylcarnitines, and are transferable to germ-free mice by fecal transplant. Thus, changes in gut microbiota can control brain insulin signaling and metabolite levels, and this leads to altered neurobehaviors.
Have you ever been on a diet but didn’t hit your goal weight? Your gut bacteria may be part of the explanation.
New research suggests the mix of microbes in our guts can either help — or hinder — weight-loss efforts.
“We started with the premise that people have different microbial makeups, and this could influence how well they do with dieting,” explains Purna Kashyap, a gastroenterologist at the Mayo Clinic in Rochester, Minn.
As part of the study, Kashyap and his collaborators tracked the progress of people who were enrolled in a lifestyle-intervention program for weight loss. The participants were advised to follow a low-calorie diet, and they were tracked closely for about three months.
“We found that people who lost at least 5 percent of their body weight had a different gut bacteria as compared to those who did not lose 5 percent of their body weight,” Kashyap explains. Their findings are published in the journal Mayo Clinic Proceedings.
The successful dieters had an increased abundance of a bacteria called Phascolarctobacterium, whereas another bacteria, Dialister, was associated with a failure to lose the weight. And, Kashyap says it’s likely that there are other types of bacteria that might influence dieting as well.
So, how might bacteria influence weight loss? It turns out we can get a significant number of calories from our microbes.
Here’s how it works: Consider what happens when you eat an apple. You digest most of it.
“But there’s a certain part of the apple we can’t absorb,” explains Martin Blaser, a professor in the Department of Microbiology at NYU Langone Medical Center. “We don’t have the right enzymes to digest every bit of [the apple], but our bacteria can.”
Think of it this way: The bacteria eat what we can’t.
And, in the process, they produce byproducts that we can digest. So these byproducts become another source of calories for us.
The new study suggests that certain bacteria — or mix of bacteria — may be more efficient at creating “extra” calories for us to digest.
“Somewhere between 5 to 15 percent of all our calories come from that kind of digestion, where the microbes are providing energy for us, that we couldn’t [otherwise] get,” Blaser explains.
This calorie boost could be beneficial if food were scarce. “If times were bad, if we were starving, we’d really welcome it,” Blaser says.
But at a time when many people want to lose weight, these extra calories may be an unwanted gift.
But the study was small — just 26 participants. Now, researchers want to conduct a larger, follow-up study, including dieters from different geographic regions, to see if they can reproduce the results.
“If two studies show the same thing, then we’re on more solid ground,” Blaser says. He was not involved in the research, but agreed to review the findings for NPR. For now, he says these findings are intriguing but preliminary.
Down the road, if the results hold up in a larger group, it could lead to more tailored dieting approaches. “What we would hope to do is to be able to individualize care for people,” Kashyap says. “And we’d also try to develop new probiotics, which we could use to change the microbial makeup.”
Probiotics that are currently on the market would not be effective. The idea is to develop a new product that includes the specific types of bacteria linked to successful dieting.
But it’s not so simple to manipulate the mix of microbes in our guts. Identifying the organism — or organisms — that are thought to be beneficial is just the first step.
Next, the organisms would need to be cultivated and mass-produced in order to create a new probiotic. “Some bacteria are difficult to work with,” so it could be challenging, says Blaser.
So, if it’s possible to produce a probiotic for dieters based on this research, “it’s at least some years off,” Blaser says.
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