BACKGROUND An altered (dysbiosis) and unhealthy status of the gut microbiota is usually responsible for a reduction of short chain fatty acids (SCFAs) concentration. SCFAs obtained from the carbohydrate fermentation p...BACKGROUND An altered (dysbiosis) and unhealthy status of the gut microbiota is usually responsible for a reduction of short chain fatty acids (SCFAs) concentration. SCFAs obtained from the carbohydrate fermentation processes are crucial in maintaining gut homeostasis and their determination in stool samples could provide a faster, reliable and cheaper method to highlight the presence of an intestinal dysbiosis and a biomarker for various gut diseases. We hypothesize that different intestinal diseases, such as celiac disease (CD), adenomatous polyposis (AP) and colorectal cancer (CRC) could display a particular fecal SCFAs’ signature. AIM To compare the fecal SCFAs’ profiles of CD, AP, CRC patients and healthy controls, using the same analytical method. METHODS In this cross-sectional study, we defined and compared the SCFAs’ concentration in fecal samples of 9 AP, 16 CD, 19 CRC patients and 16 healthy controls (HC). The SCFAs’ analysis were performed using a gas-chromatography coupled with mass spectrometry method. Data analysis was carried out using Wilcoxon ranksum test to assess pairwise differences of SCFAs’ profiles, partial least squaresdiscriminate analysis (PLS-DA) to determine the status membership based on distinct SCFAs’ profiles, and Dirichlet regression to determine factors influencing concentration levels of SCFAs. RESULTS We have not observed any difference in the SCFAs’ amount and composition between CD and healthy control. On the contrary, the total amount of SCFAs was significantly lower in CRC patients compared to HC (P = 0.044) and CD (P = 0.005). Moreover, the SCFAs’ percentage composition was different in CRC and AP compared to HC. In detail, HC displayed higher percentage of acetic acid (P value = 1.3 × 10-6) and a lower amount of butyric (P value = 0.02192), isobutyric (P value = 7.4 × 10-5), isovaleric (P value = 0.00012) and valeric (P value = 0.00014) acids compared to CRC patients. AP showed a lower abundance of acetic acid (P value = 0.00062) and higher percentages of propionic (P value = 0.00433) and isovaleric (P value = 0.00433) acids compared to HC. Moreover, AP showed higher levels of propionic acid (P value = 0.03251) and a lower level of isobutyric acid (P value = 0.00427) in comparison to CRC. The PLS-DA model demonstrated a significant separation of CRC and AP groups from HC, although some degree of overlap was observed between CRC and AP. CONCLUSION Analysis of fecal SCFAs shows the potential to provide a non-invasive means of diagnosis to detect patients with CRC and AP, while CD patients cannot be discriminated from healthy subjects.展开更多
AIM:To investigate differences in microbes and short chain fatty acid(SCFA) levels in stool samples from Hispanic and non-Hispanic African American,American Indian,and White participants.METHODS:Stool samples from twe...AIM:To investigate differences in microbes and short chain fatty acid(SCFA) levels in stool samples from Hispanic and non-Hispanic African American,American Indian,and White participants.METHODS:Stool samples from twenty participants were subjected to analysis for relative levels of viable bacteria and for SCFA levels.Additionally,the samples were subjected to 16 S r RNA gene pyrosequencing for identification of bacteria present in the stool.We used a metagenome functional prediction technique to analyze genome copy numbers and estimate the abundance of butyrate kinase in all samples.RESULTS:We found that African Americans had significantly lower levels of acetate,butyrate,and total SCFAs than all other racial/ethnic groups.We also found that participant microbial profiles differed by racial/ethnic group.African Americans had significantly more Firmicutes than Whites,with enriched Ruminococcaceae.The Firmicutes /Bacteroidetes ratio was also significantly higher for African Americans than for Whites(P =0.049).We found Clostridium levels to be significantly and inversely related to total SCFA levels(P =0.019) and we found Bacteroides to be positively associated(P =0.027) and Clostridium to be negatively associated(P =0.012) with levels of butyrate.We also identified a correlation between copy number for a butyrate kinase predicted from 16 S r RNA gene abundance and levels of butyrate in stool.CONCLUSION:The identified differences in gut flora and SCFA levels may relate to colorectal cancer mortality differentials and may be useful as targets for future clinical and behavioral interventions.展开更多
The accumulation of short-chain fatty acids （SCFAs）, a preferred carbon source for enhanced biological phosphorus removal microbes, was significantly improved when waste activated sludge （WAS） was fermented at pH ...The accumulation of short-chain fatty acids （SCFAs）, a preferred carbon source for enhanced biological phosphorus removal microbes, was significantly improved when waste activated sludge （WAS） was fermented at pH 10. The kinetics of WAS hydrolysis and SCFAs production at pH 10 was investigated. It was observed that during WAS anaerobic fermentation the accumulation of SCFAs was limited by the hydrolysis process, and both the hydrolysis of WAS particulate COD and the accumulation of SCFAs followed first-order kinetics. The hydrolysis and SCFAs accumulation rate constants increased with increasing temperature from 10 to 35℃, which could be described by the Arrhenius equation. The kinetic data further indicated that SCFAs production at pH 10 was a biological process. Compared with the experiment of pH uncontrolled （blank test）, both the rate constants of WAS hydrolysis and SCFAs accumulation at 20℃ were improved significantly when WAS was fermented at pH 10.展开更多
γ-Polyglutamic acid (γ-PGA) is a major component of Natto. We hypothesized that γ-PGA could reduce postprandial glucose rise and plasma glucose levels. Mice were fed a 0.1% γ-PGA—containing diet or control diet f...γ-Polyglutamic acid (γ-PGA) is a major component of Natto. We hypothesized that γ-PGA could reduce postprandial glucose rise and plasma glucose levels. Mice were fed a 0.1% γ-PGA—containing diet or control diet for 91 days. Maltose and starch tolerance tests were performed, and plasma lipids, glucose levels, and caecal short chain fatty acids (SCFAs) were measured. Mice were co-administered γ-PGA and starch to suppress the initial rise in blood glucose levels. Blood glucose levels at 15 min were significantly lower in the PGA group than in the Con group (P 0.05). The plasma glucose level and NEFA level were also significantly lower in the PGA group (P 0.05), and caecal acetic acid/total caecal SCFAs ratio was significantly increased in the PGA group (P 0.05). Significant negative correlations existed between the caecal acetic acid/propionic acid ratio and the weight of visceral fat/BW (r =?-0.57, P = 0.0318). Our results suggest that γ-PGA may effectively prevent metabolic syndrome by lowering blood glucose levels.展开更多
The impact of the gut microbiota is not limited to the intestine, but its interaction with the host produces active metabolites, which can be transported by the blood circulation to play important roles in various par...The impact of the gut microbiota is not limited to the intestine, but its interaction with the host produces active metabolites, which can be transported by the blood circulation to play important roles in various parts of the body. Among them, short-chain fatty acids (SCFAs), as important active products of gut bacteria, have been shown to exert anti-inflammatory and immunomodulatory effects and can play active roles as signaling molecules in the development of various intestinal and extraintestinal diseases, such as inflammatory bowel disease, colon cancer, multiple sclerosis, hypertension, allergic airway disease, obesity, diabetes, kidney disease, rheumatoid arthritis, etc. In this way, modulation of the intestinal microbiota and metabolism-active substances has gradually become a popular therapeutic method for many diseases of organs beyond the gut. To find new therapeutic targets for major human health problems, this article reviews the research on SCFAs in extraintestinal diseases.展开更多
Short chain fatty acids(SCFA)exist in dietary foods and are produced by the fermentation of gut microbiota,and are considered an important element for regulating host health.Through blood circulation,SCFA produced in ...Short chain fatty acids(SCFA)exist in dietary foods and are produced by the fermentation of gut microbiota,and are considered an important element for regulating host health.Through blood circulation,SCFA produced in the gut and obtained from foods have an impact on the intestinal health as well as vital organs of the host.It has been recognized that the gut is the“vital organ”in the host.As the gut microbial metabolites,SCFA could create an“axis”connecting the gut and to other organs.Therefore,the“gut-organ axes”have become a focus of research in recent years to analyze organism health.In this review,we summarized the sources,absorption properties,and the function of SCFA in both gut and other peripheral tissues(brain,kidney,liver,lung,bone and cardiovascular)in the way of“gut-organ axes”.Short chain fatty acids exert both beneficial and pathological role in gut and other organs in various ways,in which the beneficial effects are more pronounced.In addition,the beneficial effects are reflected in both preventive and therapeutic effects.More importantly,the mechanisms behinds the gut and other tissues provided insight into the function of SCFA,assisting in the development of novel preventive and therapeutic strategies for maintaining the host health.展开更多
Short-chain fatty acids (SCFA) play an important role in human biochemistry. They originate primarily from the digestive system through carbohydrates microbial fermentation. Most SCFA produced in the colon are absorbe...Short-chain fatty acids (SCFA) play an important role in human biochemistry. They originate primarily from the digestive system through carbohydrates microbial fermentation. Most SCFA produced in the colon are absorbed by the intestinal wall and enter the bloodstream to be distributed throughout the body for multiple purposes. At the intestinal level, SCFA play a role in controlling fat storage and fatty acid metabolism. The effects of these beneficial compounds therefore concern overall health. They facilitate energy expenditure and are valuable allies in the fight against obesity and diabetes. SCFA are also involved in the regulation of the levels of several neurotransmitters such as GABA (γ-aminobutyric acid), glutamate, serotonin, dopamine, and norepinephrine. Their role is also highlighted in many inflammatory and neurodegenerative diseases such as Alzheimer’s disease (AD) or Parkinson’s disease (PD). To have a realistic picture of the distribution of SCFA in different biological compartments of the human body, we propose to study SCFA simultaneously in five human biological samples: feces, saliva, serum, cerebrospinal fluid (CSF), and urine, as well as in Dried Blood Spot (DBS). To evaluate their concentration and repeatability, we used 10 aliquots from pooled samples, analyzed by 3-nitrophenylhydrazine (3-NPH) derivation and liquid chromatography coupled with high sensitivity mass spectrometry (LC-QqQ-MS). We also evaluated the SCFA assay on Dried Blood Spot (DBS). In this work, we adapted the pre-analytical parts for each sample to be able to use a common calibration curve, thus facilitating multi-assay quantification studies and so being less time-consuming. Moreover, we proposed new daughter ions from the same neutral loss (43 Da) to quantify SCFAs, thus improving the sensitivity. In conclusion, our methodology, based on a unique calibration curve for all samples for each SCFA, is well-suited to quantified them in a clinical context.展开更多
基金Supported by Italian Society for Celiac Disease and Foundation for Celicac Disease,No.007_FC_2016Regione Toscana(The Programma Attuativo Regionale Toscana funded by FAS),No.MICp ROBIMM
文摘BACKGROUND An altered (dysbiosis) and unhealthy status of the gut microbiota is usually responsible for a reduction of short chain fatty acids (SCFAs) concentration. SCFAs obtained from the carbohydrate fermentation processes are crucial in maintaining gut homeostasis and their determination in stool samples could provide a faster, reliable and cheaper method to highlight the presence of an intestinal dysbiosis and a biomarker for various gut diseases. We hypothesize that different intestinal diseases, such as celiac disease (CD), adenomatous polyposis (AP) and colorectal cancer (CRC) could display a particular fecal SCFAs’ signature. AIM To compare the fecal SCFAs’ profiles of CD, AP, CRC patients and healthy controls, using the same analytical method. METHODS In this cross-sectional study, we defined and compared the SCFAs’ concentration in fecal samples of 9 AP, 16 CD, 19 CRC patients and 16 healthy controls (HC). The SCFAs’ analysis were performed using a gas-chromatography coupled with mass spectrometry method. Data analysis was carried out using Wilcoxon ranksum test to assess pairwise differences of SCFAs’ profiles, partial least squaresdiscriminate analysis (PLS-DA) to determine the status membership based on distinct SCFAs’ profiles, and Dirichlet regression to determine factors influencing concentration levels of SCFAs. RESULTS We have not observed any difference in the SCFAs’ amount and composition between CD and healthy control. On the contrary, the total amount of SCFAs was significantly lower in CRC patients compared to HC (P = 0.044) and CD (P = 0.005). Moreover, the SCFAs’ percentage composition was different in CRC and AP compared to HC. In detail, HC displayed higher percentage of acetic acid (P value = 1.3 × 10-6) and a lower amount of butyric (P value = 0.02192), isobutyric (P value = 7.4 × 10-5), isovaleric (P value = 0.00012) and valeric (P value = 0.00014) acids compared to CRC patients. AP showed a lower abundance of acetic acid (P value = 0.00062) and higher percentages of propionic (P value = 0.00433) and isovaleric (P value = 0.00433) acids compared to HC. Moreover, AP showed higher levels of propionic acid (P value = 0.03251) and a lower level of isobutyric acid (P value = 0.00427) in comparison to CRC. The PLS-DA model demonstrated a significant separation of CRC and AP groups from HC, although some degree of overlap was observed between CRC and AP. CONCLUSION Analysis of fecal SCFAs shows the potential to provide a non-invasive means of diagnosis to detect patients with CRC and AP, while CD patients cannot be discriminated from healthy subjects.
基金Supported by The University of Kansas Cancer Center,U54CA154253 from the National Cancer Institute at the NIHthe University of Kansas Clinical Translational Science Program(Frontiers,CA123245 from the National Cancer Institute at NIH)+1 种基金1R01CA138623 from the NCI at NIHthe James Graham Brown Cancer Center,University of Louisville
文摘AIM:To investigate differences in microbes and short chain fatty acid(SCFA) levels in stool samples from Hispanic and non-Hispanic African American,American Indian,and White participants.METHODS:Stool samples from twenty participants were subjected to analysis for relative levels of viable bacteria and for SCFA levels.Additionally,the samples were subjected to 16 S r RNA gene pyrosequencing for identification of bacteria present in the stool.We used a metagenome functional prediction technique to analyze genome copy numbers and estimate the abundance of butyrate kinase in all samples.RESULTS:We found that African Americans had significantly lower levels of acetate,butyrate,and total SCFAs than all other racial/ethnic groups.We also found that participant microbial profiles differed by racial/ethnic group.African Americans had significantly more Firmicutes than Whites,with enriched Ruminococcaceae.The Firmicutes /Bacteroidetes ratio was also significantly higher for African Americans than for Whites(P =0.049).We found Clostridium levels to be significantly and inversely related to total SCFA levels(P =0.019) and we found Bacteroides to be positively associated(P =0.027) and Clostridium to be negatively associated(P =0.012) with levels of butyrate.We also identified a correlation between copy number for a butyrate kinase predicted from 16 S r RNA gene abundance and levels of butyrate in stool.CONCLUSION:The identified differences in gut flora and SCFA levels may relate to colorectal cancer mortality differentials and may be useful as targets for future clinical and behavioral interventions.
基金supported by the Hi-TechResearch and Development Program (863) of China(No. 2007AA06Z326)the Key Projects of National Wa-ter Pollution Control and Management of China (No.2008ZX07315-003, 2008ZX07316-002)the Key Lab-oratory of Environmental Science and Engineering ofJiangsu Province (No. ZD071201).
文摘The accumulation of short-chain fatty acids （SCFAs）, a preferred carbon source for enhanced biological phosphorus removal microbes, was significantly improved when waste activated sludge （WAS） was fermented at pH 10. The kinetics of WAS hydrolysis and SCFAs production at pH 10 was investigated. It was observed that during WAS anaerobic fermentation the accumulation of SCFAs was limited by the hydrolysis process, and both the hydrolysis of WAS particulate COD and the accumulation of SCFAs followed first-order kinetics. The hydrolysis and SCFAs accumulation rate constants increased with increasing temperature from 10 to 35℃, which could be described by the Arrhenius equation. The kinetic data further indicated that SCFAs production at pH 10 was a biological process. Compared with the experiment of pH uncontrolled （blank test）, both the rate constants of WAS hydrolysis and SCFAs accumulation at 20℃ were improved significantly when WAS was fermented at pH 10.
文摘γ-Polyglutamic acid (γ-PGA) is a major component of Natto. We hypothesized that γ-PGA could reduce postprandial glucose rise and plasma glucose levels. Mice were fed a 0.1% γ-PGA—containing diet or control diet for 91 days. Maltose and starch tolerance tests were performed, and plasma lipids, glucose levels, and caecal short chain fatty acids (SCFAs) were measured. Mice were co-administered γ-PGA and starch to suppress the initial rise in blood glucose levels. Blood glucose levels at 15 min were significantly lower in the PGA group than in the Con group (P 0.05). The plasma glucose level and NEFA level were also significantly lower in the PGA group (P 0.05), and caecal acetic acid/total caecal SCFAs ratio was significantly increased in the PGA group (P 0.05). Significant negative correlations existed between the caecal acetic acid/propionic acid ratio and the weight of visceral fat/BW (r =?-0.57, P = 0.0318). Our results suggest that γ-PGA may effectively prevent metabolic syndrome by lowering blood glucose levels.
文摘The impact of the gut microbiota is not limited to the intestine, but its interaction with the host produces active metabolites, which can be transported by the blood circulation to play important roles in various parts of the body. Among them, short-chain fatty acids (SCFAs), as important active products of gut bacteria, have been shown to exert anti-inflammatory and immunomodulatory effects and can play active roles as signaling molecules in the development of various intestinal and extraintestinal diseases, such as inflammatory bowel disease, colon cancer, multiple sclerosis, hypertension, allergic airway disease, obesity, diabetes, kidney disease, rheumatoid arthritis, etc. In this way, modulation of the intestinal microbiota and metabolism-active substances has gradually become a popular therapeutic method for many diseases of organs beyond the gut. To find new therapeutic targets for major human health problems, this article reviews the research on SCFAs in extraintestinal diseases.
基金supported by the National Key R&D Program of China (2022YFD1600104)the earmarked fund for CARS (CARS-36)the Agricultural Science and Technology Innovation Program (ASTIP-IAS12).
文摘Short chain fatty acids(SCFA)exist in dietary foods and are produced by the fermentation of gut microbiota,and are considered an important element for regulating host health.Through blood circulation,SCFA produced in the gut and obtained from foods have an impact on the intestinal health as well as vital organs of the host.It has been recognized that the gut is the“vital organ”in the host.As the gut microbial metabolites,SCFA could create an“axis”connecting the gut and to other organs.Therefore,the“gut-organ axes”have become a focus of research in recent years to analyze organism health.In this review,we summarized the sources,absorption properties,and the function of SCFA in both gut and other peripheral tissues(brain,kidney,liver,lung,bone and cardiovascular)in the way of“gut-organ axes”.Short chain fatty acids exert both beneficial and pathological role in gut and other organs in various ways,in which the beneficial effects are more pronounced.In addition,the beneficial effects are reflected in both preventive and therapeutic effects.More importantly,the mechanisms behinds the gut and other tissues provided insight into the function of SCFA,assisting in the development of novel preventive and therapeutic strategies for maintaining the host health.
文摘Short-chain fatty acids (SCFA) play an important role in human biochemistry. They originate primarily from the digestive system through carbohydrates microbial fermentation. Most SCFA produced in the colon are absorbed by the intestinal wall and enter the bloodstream to be distributed throughout the body for multiple purposes. At the intestinal level, SCFA play a role in controlling fat storage and fatty acid metabolism. The effects of these beneficial compounds therefore concern overall health. They facilitate energy expenditure and are valuable allies in the fight against obesity and diabetes. SCFA are also involved in the regulation of the levels of several neurotransmitters such as GABA (γ-aminobutyric acid), glutamate, serotonin, dopamine, and norepinephrine. Their role is also highlighted in many inflammatory and neurodegenerative diseases such as Alzheimer’s disease (AD) or Parkinson’s disease (PD). To have a realistic picture of the distribution of SCFA in different biological compartments of the human body, we propose to study SCFA simultaneously in five human biological samples: feces, saliva, serum, cerebrospinal fluid (CSF), and urine, as well as in Dried Blood Spot (DBS). To evaluate their concentration and repeatability, we used 10 aliquots from pooled samples, analyzed by 3-nitrophenylhydrazine (3-NPH) derivation and liquid chromatography coupled with high sensitivity mass spectrometry (LC-QqQ-MS). We also evaluated the SCFA assay on Dried Blood Spot (DBS). In this work, we adapted the pre-analytical parts for each sample to be able to use a common calibration curve, thus facilitating multi-assay quantification studies and so being less time-consuming. Moreover, we proposed new daughter ions from the same neutral loss (43 Da) to quantify SCFAs, thus improving the sensitivity. In conclusion, our methodology, based on a unique calibration curve for all samples for each SCFA, is well-suited to quantified them in a clinical context.
