The gut microbiome of patients with colorectal cancer (CRC) was less diverse than that of matched patients without cancer, and the presence of some taxa was associated with increased CRC risk, according to research published online December 6 in the Journal of the National Cancer Institute.
"Because of the potentially modifiable nature of the gut bacteria, our findings may have implications for CRC prevention," write Jiyoung Ahn, PhD, assistant professor of population health and a member of the NYU Cancer Institute, New York University School of Medicine, New York City, and colleagues.
The results came from an analysis of fecal bacterial DNA from 47 patients with CRC and 94 control participants matched to the CRC group by sex and body mass index. The investigators amplified 794,217 16S rRNA genes and then classified the sequences taxonomically.
They note that this is the first study to compare the gut microbiomes of people with and without CRC that included multiple comparisons of bacteria while controlling for possible confounders.
The researchers found decreased microbiome community diversity in patients with CRC , compared with that of healthy participants(P= .02). In an analysis by taxa, patients with CRC had lower relative abundances of Clostridia, at 68.6% compared with 77.8% in people without CRC. In contrast, patients with CRC carried a higher relative abundance of Fusobacterium (31.9% vs 11.7% for control patients).
A higher relative abundance of Fusobacterium was associated with increased CRC risk (multivariable odds ratio [OR], 4.11; 95% confidence interval [CI], 1.62 - 10.47), after adjusting for age, sex, body mass index, race, smoking, and sequencing batch.
Actinobacteria Atopobium (OR, 14.36; 95% CI, 2.78 - 74.30; P < .001) and the Bacteriodetes Porphyromonas(OR, 5.17; 95% CI, 1.75 - 15.25; P = .001) were also associated with CRC risk. The Gram-positiveAtopobium is associated with Crohn's disease and is reported to inhibit colon cancer apoptosis in vitro.Polyphyromonas, which is often found in the mouth and gastrointestinal tract, is associated with periodontal disease.
Patients with CRC tended to have more Bacteroidetes phylum bacteria (16.2% relative abundance vs 9.9% for control participants) and fewer Firmicutes (74.0% for patients with CRC compared with 80.3% for control participants). The depletion of Firmicutes was highest for the class Clostridia (68.6% for patients with CRC vs 77.8% for control participants; P = .005; false discovery rate–adjusted P < .05). Among the depleted taxa was Coprococcus in the Clostridia family Lachnospiracea. Coprococcus is responsible for the efficient fermentation of dietary fiber and other complex carbohydrates into butyrate, a major colonic metabolite that may inhibit colonic inflammation and carcinogenesis, the authors write.
In an additional assay using quantitative polymerase chain reaction for Porphyromonas and Fusobacterium, the association between CRC and these taxa remained significant. In that study, the OR for CRC with the presence of Porphyromonas was 1.44 (P = .05), and the OR for CRC with the presence of Fusobacteriumwas 1.44 (P = 0.01).
Welcome to my collection of health articles. Most of them contain little nuggets of health wisdom that we can easily apply to our daily lives. As you can gather, I've been consuming all sorts of supplements over the years, most of them from iherb. They deliver on time (DHL), and prices are good. If you're a first-time buyer, use my code 'pot089' to enjoy up to $10 off.
Showing posts with label gut flora. Show all posts
Showing posts with label gut flora. Show all posts
Wednesday, 8 January 2014
Friday, 12 April 2013
Carnitine in red meat ups atherosclerosis risk via gut flora
Research in mice and human volunteers has suggested a mechanism that may contribute to an association between eating red meat and increased risk of cardiovascular disease[1]. It involves microbes in the gut.
People who regularly eat red meat have an increased colonization of intestinal bacteria that break down the carnitine in red meat into a metabolite that promotes increased cholesterol deposition in the artery wall, the researchers report. Their study was published online April 7, 2013 inNature Medicine.
Energy drinks are another major source of carnitine. If someone regularly eats red meat or drinks energy drinks, "microbes that like carnitine become more abundant [in the gut], and now you are much more capable of making this metabolite . . . trimethylamine-N-oxide (TMAO)," he said. "This paper showed [that TMAO] . . . essentially leads to an enhanced capacity to deposit cholesterol on the cells of your artery wall."
Previously, the researchers showed that dietary choline and phosphatidylcholine (lecithin) are metabolized in mice and humans by intestinal microbes to produce trimethylamine, which is rapidly metabolized to TMAO, which is linked to accelerated atherosclerosis. Hypothesizing that carnitine, which has a similar molecular structure to choline, behaves this way, the researchers performed a series of experiments.
Carnitine linked to TMAO levels
First, they showed, for what they believe is the first time, that humans need gut microbes to form TMAO from dietary carnitine. After an overnight fast, volunteer omnivores were given a carnitine challenge--they were fed a capsule of carnitine plus an 8-oz sirloin steak--and their TMAO plasma and urine levels were measured. The volunteers were then given oral, broad-spectrum antibiotics for a week to suppress their gut microbes, after which they received a second carnitine challenge. Then after three weeks to allow their gut organisms to repopulate, they received a third carnitine challenge. Their TMAO levels were almost undetectable after the antibiotic regimen, but the levels rebounded after their gut flora repopulated.
The researchers also showed that after ingesting carnitine capsules, vegans and vegetarians produced markedly lower levels of TMAO than omnivores.
TMAO, not carnitine, drives CVD
Next, in a cohort of 2595 subjects undergoing elective cardiovascular evaluation, the researchers determined that increased plasma carnitine was associated with increased risk of having or soon developing CAD, peripheral artery disease (PAD), or other CVD. However, after adjustment for traditional cardiovascular risk factors, an elevated carnitine concentration predicted a higher three-year risk of MI, stroke, or death only in subjects with high plasma TMAO levels. Thus TMAO, not carnitine, drives the cardiovascular outcomes, the researchers conclude.
Their mouse studies suggest a possible, multifaceted mechanism for the development of atherosclerosis. In mice, dietary carnitine promoted cholesterol buildup in the artery wall, which was completely inhibited after treatment with an antibiotic cocktail. In other mice with intact intestinal microbes, receiving TMAO and carnitine or lecithin led to inhibition of the reverse cholesterol transport pathway.
For now, eat well; in future, also take a pill?
Does this mean that physicians should advise all their patients to become vegetarians and avoid drinking energy drinks? Hazen says that people need to be aware that "a can of an energy drink can have more carnitine than a porterhouse steak." Carnitine is obtained from many sources, since it is derived from lysine, the most abundant amino acid in animal and vegetable protein in the diet, he noted.
For now, "it makes sense to adhere to a lower-cholesterol, lower-saturated-fat diet [that will be] more heart healthy in terms of decreasing the nutrients that give rise to forming TMAO, [since] this may be one of the hidden contributors to heart disease."
In the future, there might be a TMAO test and a drug that targets TMAO, Hazen speculated. "Measuring TMAO can be a very strong predictor of cardiovascular risk, and it will become a test that is available for clinical use in the future," he hypothesized. "Down the road, we think we are going to be able to go after this, just like we take a statin . . . to decrease the [risk of] development of heart disease."
Source: http://www.medscape.com/viewarticle/782236?nlid=30183_1301&src=wnl_edit_dail
People who regularly eat red meat have an increased colonization of intestinal bacteria that break down the carnitine in red meat into a metabolite that promotes increased cholesterol deposition in the artery wall, the researchers report. Their study was published online April 7, 2013 inNature Medicine.
Energy drinks are another major source of carnitine. If someone regularly eats red meat or drinks energy drinks, "microbes that like carnitine become more abundant [in the gut], and now you are much more capable of making this metabolite . . . trimethylamine-N-oxide (TMAO)," he said. "This paper showed [that TMAO] . . . essentially leads to an enhanced capacity to deposit cholesterol on the cells of your artery wall."
Previously, the researchers showed that dietary choline and phosphatidylcholine (lecithin) are metabolized in mice and humans by intestinal microbes to produce trimethylamine, which is rapidly metabolized to TMAO, which is linked to accelerated atherosclerosis. Hypothesizing that carnitine, which has a similar molecular structure to choline, behaves this way, the researchers performed a series of experiments.
Carnitine linked to TMAO levels
First, they showed, for what they believe is the first time, that humans need gut microbes to form TMAO from dietary carnitine. After an overnight fast, volunteer omnivores were given a carnitine challenge--they were fed a capsule of carnitine plus an 8-oz sirloin steak--and their TMAO plasma and urine levels were measured. The volunteers were then given oral, broad-spectrum antibiotics for a week to suppress their gut microbes, after which they received a second carnitine challenge. Then after three weeks to allow their gut organisms to repopulate, they received a third carnitine challenge. Their TMAO levels were almost undetectable after the antibiotic regimen, but the levels rebounded after their gut flora repopulated.
The researchers also showed that after ingesting carnitine capsules, vegans and vegetarians produced markedly lower levels of TMAO than omnivores.
TMAO, not carnitine, drives CVD
Next, in a cohort of 2595 subjects undergoing elective cardiovascular evaluation, the researchers determined that increased plasma carnitine was associated with increased risk of having or soon developing CAD, peripheral artery disease (PAD), or other CVD. However, after adjustment for traditional cardiovascular risk factors, an elevated carnitine concentration predicted a higher three-year risk of MI, stroke, or death only in subjects with high plasma TMAO levels. Thus TMAO, not carnitine, drives the cardiovascular outcomes, the researchers conclude.
Their mouse studies suggest a possible, multifaceted mechanism for the development of atherosclerosis. In mice, dietary carnitine promoted cholesterol buildup in the artery wall, which was completely inhibited after treatment with an antibiotic cocktail. In other mice with intact intestinal microbes, receiving TMAO and carnitine or lecithin led to inhibition of the reverse cholesterol transport pathway.
For now, eat well; in future, also take a pill?
Does this mean that physicians should advise all their patients to become vegetarians and avoid drinking energy drinks? Hazen says that people need to be aware that "a can of an energy drink can have more carnitine than a porterhouse steak." Carnitine is obtained from many sources, since it is derived from lysine, the most abundant amino acid in animal and vegetable protein in the diet, he noted.
For now, "it makes sense to adhere to a lower-cholesterol, lower-saturated-fat diet [that will be] more heart healthy in terms of decreasing the nutrients that give rise to forming TMAO, [since] this may be one of the hidden contributors to heart disease."
In the future, there might be a TMAO test and a drug that targets TMAO, Hazen speculated. "Measuring TMAO can be a very strong predictor of cardiovascular risk, and it will become a test that is available for clinical use in the future," he hypothesized. "Down the road, we think we are going to be able to go after this, just like we take a statin . . . to decrease the [risk of] development of heart disease."
Source: http://www.medscape.com/viewarticle/782236?nlid=30183_1301&src=wnl_edit_dail
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