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These findings improve our understanding of IBD pathogenesis and disease course, and could prove valuable in biomarker research, reported lead author Gary D. Wu, MD, of the University of Pennsylvania, Philadelphia, and colleagues.
In health, carnitine and acylcarnitines aid in fatty acid transport, the investigators wrote in September in Cellular and Molecular Gastroenterology and Hepatology. Acylcarnitines are also involved in metabolic signaling, and in the absence of sufficient short-chain fatty acids may serve as an alternative energy source for the intestinal epithelium.
“Recently, we and others have shown that fecal acylcarnitines are increased in patients with IBD, especially during dysbiosis,” they noted. “However, the mechanism(s) responsible for the increase of fecal acylcarnitines in IBD and their biological function have not been elucidated.”
The present study aimed to address this knowledge gap by characterizing both carnitine and acylcarnitines in pediatric IBD.
First, the investigators confirmed that both carnitine and acylcarnitines were elevated in fecal samples from pediatric patients with IBD.
Next, they analyzed fecal samples from subjects in the Food and Resulting Microbiota and Metabolome (FARMM) study, which compared microbiota recovery after gut purge and antibiotics among participants eating an omnivorous diet, a vegan diet, or an exclusive enteral nutrition (EEN) diet lacking in fiber. After the antibiotics, levels of fecal carnitine and acylcarnitines increased significantly in all groups, suggesting that microbiota were consuming these molecules.
To clarify the relationship between inflammation and levels of carnitine and acylcarnitines in the absence of microbiota, Dr. Wu and colleagues employed a germ-free mouse model with dextran sodium sulfate (DSS)–induced colitis. Levels of both molecule types were significantly increased in bile and plasma of mice with colitis versus those that were not exposed to DSS.
“Because the gut microbiota consumes both carnitine and acylcarnitines, these results are consistent with the notion that the increase of these metabolites in the feces of patients with IBD is driven by increased biliary delivery of acylcarnitines to the lumen combined with the reduced number and function of mitochondria in the colonic epithelium as previously reported,” the investigators wrote.
Further experiments with plated cultures and mice revealed that various bacterial species consumed carnitine and acylcarnitines in distinct patterns. Enterobacteriaceae demonstrated a notable proclivity for consumption in vitro and within the murine gut.
“As a high-dimensional analytic feature, the pattern of fecal acylcarnitines, perhaps together with bacterial taxonomy, may have utility as a biomarker for the presence or prognosis of IBD,” Dr. Wu and colleagues concluded. “In addition, based on currently available information about the impact of carnitine on the biology of Enterobacteriaceae, acylcarnitines also may have an important functional effect on the biology of the gut microbiota that is relevant to the pathogenesis or course of disease in patients with IBD.”
The study was supported by the Crohn’s and Colitis Foundation, the PennCHOP Microbiome Program, the Penn Center for Nutritional Science and Medicine, and others. The investigators disclosed no conflicts of interest.
The description of noninvasive biomarkers for inflammatory bowel disease (IBD) is key to better characterizing the disease pathogenesis. In this new publication, Lemons et al. describe deleterious effects of gut luminal carnitine and acylcarnitine in pediatric IBD patients, showing that these metabolites can serve as energy substrates to the microbiota, especially Enterobacteriaceae, promoting the growth of pathobionts and contributing to the persistence of dysbiosis which, in turn, may foster the course of IBD. In fact, acylcarnitine had been highlighted as a potential new target for IBD during dysbiosis by a previous multi-omics study of the gut microbiome. Moreover, Dr. Gary Wu’s team has shown that the intestinal epithelium can uptake and use acylcarnitine as an alternative source for energy production. However, epithelial mitochondrial dysfunction triggered by inflammation reduces the capacity of colonocytes to consume long-chain fatty acids, thus enhancing the fecal levels of acylcarnitine as described in IBD patients.
The description of noninvasive biomarkers for inflammatory bowel disease (IBD) is key to better characterizing the disease pathogenesis. In this new publication, Lemons et al. describe deleterious effects of gut luminal carnitine and acylcarnitine in pediatric IBD patients, showing that these metabolites can serve as energy substrates to the microbiota, especially Enterobacteriaceae, promoting the growth of pathobionts and contributing to the persistence of dysbiosis which, in turn, may foster the course of IBD. In fact, acylcarnitine had been highlighted as a potential new target for IBD during dysbiosis by a previous multi-omics study of the gut microbiome. Moreover, Dr. Gary Wu’s team has shown that the intestinal epithelium can uptake and use acylcarnitine as an alternative source for energy production. However, epithelial mitochondrial dysfunction triggered by inflammation reduces the capacity of colonocytes to consume long-chain fatty acids, thus enhancing the fecal levels of acylcarnitine as described in IBD patients.
The description of noninvasive biomarkers for inflammatory bowel disease (IBD) is key to better characterizing the disease pathogenesis. In this new publication, Lemons et al. describe deleterious effects of gut luminal carnitine and acylcarnitine in pediatric IBD patients, showing that these metabolites can serve as energy substrates to the microbiota, especially Enterobacteriaceae, promoting the growth of pathobionts and contributing to the persistence of dysbiosis which, in turn, may foster the course of IBD. In fact, acylcarnitine had been highlighted as a potential new target for IBD during dysbiosis by a previous multi-omics study of the gut microbiome. Moreover, Dr. Gary Wu’s team has shown that the intestinal epithelium can uptake and use acylcarnitine as an alternative source for energy production. However, epithelial mitochondrial dysfunction triggered by inflammation reduces the capacity of colonocytes to consume long-chain fatty acids, thus enhancing the fecal levels of acylcarnitine as described in IBD patients.
These findings improve our understanding of IBD pathogenesis and disease course, and could prove valuable in biomarker research, reported lead author Gary D. Wu, MD, of the University of Pennsylvania, Philadelphia, and colleagues.
In health, carnitine and acylcarnitines aid in fatty acid transport, the investigators wrote in September in Cellular and Molecular Gastroenterology and Hepatology. Acylcarnitines are also involved in metabolic signaling, and in the absence of sufficient short-chain fatty acids may serve as an alternative energy source for the intestinal epithelium.
“Recently, we and others have shown that fecal acylcarnitines are increased in patients with IBD, especially during dysbiosis,” they noted. “However, the mechanism(s) responsible for the increase of fecal acylcarnitines in IBD and their biological function have not been elucidated.”
The present study aimed to address this knowledge gap by characterizing both carnitine and acylcarnitines in pediatric IBD.
First, the investigators confirmed that both carnitine and acylcarnitines were elevated in fecal samples from pediatric patients with IBD.
Next, they analyzed fecal samples from subjects in the Food and Resulting Microbiota and Metabolome (FARMM) study, which compared microbiota recovery after gut purge and antibiotics among participants eating an omnivorous diet, a vegan diet, or an exclusive enteral nutrition (EEN) diet lacking in fiber. After the antibiotics, levels of fecal carnitine and acylcarnitines increased significantly in all groups, suggesting that microbiota were consuming these molecules.
To clarify the relationship between inflammation and levels of carnitine and acylcarnitines in the absence of microbiota, Dr. Wu and colleagues employed a germ-free mouse model with dextran sodium sulfate (DSS)–induced colitis. Levels of both molecule types were significantly increased in bile and plasma of mice with colitis versus those that were not exposed to DSS.
“Because the gut microbiota consumes both carnitine and acylcarnitines, these results are consistent with the notion that the increase of these metabolites in the feces of patients with IBD is driven by increased biliary delivery of acylcarnitines to the lumen combined with the reduced number and function of mitochondria in the colonic epithelium as previously reported,” the investigators wrote.
Further experiments with plated cultures and mice revealed that various bacterial species consumed carnitine and acylcarnitines in distinct patterns. Enterobacteriaceae demonstrated a notable proclivity for consumption in vitro and within the murine gut.
“As a high-dimensional analytic feature, the pattern of fecal acylcarnitines, perhaps together with bacterial taxonomy, may have utility as a biomarker for the presence or prognosis of IBD,” Dr. Wu and colleagues concluded. “In addition, based on currently available information about the impact of carnitine on the biology of Enterobacteriaceae, acylcarnitines also may have an important functional effect on the biology of the gut microbiota that is relevant to the pathogenesis or course of disease in patients with IBD.”
The study was supported by the Crohn’s and Colitis Foundation, the PennCHOP Microbiome Program, the Penn Center for Nutritional Science and Medicine, and others. The investigators disclosed no conflicts of interest.
These findings improve our understanding of IBD pathogenesis and disease course, and could prove valuable in biomarker research, reported lead author Gary D. Wu, MD, of the University of Pennsylvania, Philadelphia, and colleagues.
In health, carnitine and acylcarnitines aid in fatty acid transport, the investigators wrote in September in Cellular and Molecular Gastroenterology and Hepatology. Acylcarnitines are also involved in metabolic signaling, and in the absence of sufficient short-chain fatty acids may serve as an alternative energy source for the intestinal epithelium.
“Recently, we and others have shown that fecal acylcarnitines are increased in patients with IBD, especially during dysbiosis,” they noted. “However, the mechanism(s) responsible for the increase of fecal acylcarnitines in IBD and their biological function have not been elucidated.”
The present study aimed to address this knowledge gap by characterizing both carnitine and acylcarnitines in pediatric IBD.
First, the investigators confirmed that both carnitine and acylcarnitines were elevated in fecal samples from pediatric patients with IBD.
Next, they analyzed fecal samples from subjects in the Food and Resulting Microbiota and Metabolome (FARMM) study, which compared microbiota recovery after gut purge and antibiotics among participants eating an omnivorous diet, a vegan diet, or an exclusive enteral nutrition (EEN) diet lacking in fiber. After the antibiotics, levels of fecal carnitine and acylcarnitines increased significantly in all groups, suggesting that microbiota were consuming these molecules.
To clarify the relationship between inflammation and levels of carnitine and acylcarnitines in the absence of microbiota, Dr. Wu and colleagues employed a germ-free mouse model with dextran sodium sulfate (DSS)–induced colitis. Levels of both molecule types were significantly increased in bile and plasma of mice with colitis versus those that were not exposed to DSS.
“Because the gut microbiota consumes both carnitine and acylcarnitines, these results are consistent with the notion that the increase of these metabolites in the feces of patients with IBD is driven by increased biliary delivery of acylcarnitines to the lumen combined with the reduced number and function of mitochondria in the colonic epithelium as previously reported,” the investigators wrote.
Further experiments with plated cultures and mice revealed that various bacterial species consumed carnitine and acylcarnitines in distinct patterns. Enterobacteriaceae demonstrated a notable proclivity for consumption in vitro and within the murine gut.
“As a high-dimensional analytic feature, the pattern of fecal acylcarnitines, perhaps together with bacterial taxonomy, may have utility as a biomarker for the presence or prognosis of IBD,” Dr. Wu and colleagues concluded. “In addition, based on currently available information about the impact of carnitine on the biology of Enterobacteriaceae, acylcarnitines also may have an important functional effect on the biology of the gut microbiota that is relevant to the pathogenesis or course of disease in patients with IBD.”
The study was supported by the Crohn’s and Colitis Foundation, the PennCHOP Microbiome Program, the Penn Center for Nutritional Science and Medicine, and others. The investigators disclosed no conflicts of interest.
FROM CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY