scholarly journals Fatty acids produced by the gut microbiota dampen host inflammatory responses by modulating intestinal SUMOylation

2022 ◽  
Author(s):  
Chaima Ezzine ◽  
Lea Loison ◽  
Christine Bole-Feysot ◽  
Pierre Dechelotte ◽  
Moise Coeffier ◽  
...  

The gut microbiota produces a wide variety of metabolites, which interact with intestinal cells and contribute to host physiology. These metabolites regulate intestinal cell activities by modulating either gene transcription or post-translational modifications of gut proteins. The effect of gut commensal bacteria on SUMOylation, an essential ubiquitin-like modification in intestinal physiology, remains however unknown. Here, we show that short chain fatty acids (SCFAs) and branched chain fatty acids (BCFAs) produced by the gut microbiota increase protein SUMOylation in different intestinal cell lines in a pH-dependent manner. We demonstrate that these metabolites induce an oxidative stress which inactivates intestinal deSUMOylases and promotes the hyperSUMOylation of chromatin-bound proteins. In order to determine the impact of these modifications on intestinal physiology, we focused on the NF-kappaB signaling pathway, a key player in inflammation known to be regulated by SUMOylation. We demonstrated that the hyperSUMOylation induced by SCFAs/BCFAs inhibits the activation of the NF-kappaB pathway in intestinal cells by blocking the degradation of the inhibitory factor IkappaBalpha in response to TNFalpha. This results in a decrease in pro-inflammatory cytokines expression, such as IL8 or CCL20, as well as a decrease in intestinal epithelial permeability in response to TNFalpha. Together, our results reveal that fatty acids produced by gut commensal bacteria regulate intestinal physiology by modulating SUMOylation and illustrate a new mechanism of dampening of host inflammatory responses by the gut microbiota.

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Velma T. E. Aho ◽  
Madelyn C. Houser ◽  
Pedro A. B. Pereira ◽  
Jianjun Chang ◽  
Knut Rudi ◽  
...  

Abstract Background Previous studies have reported that gut microbiota, permeability, short-chain fatty acids (SCFAs), and inflammation are altered in Parkinson’s disease (PD), but how these factors are linked and how they contribute to disease processes and symptoms remains uncertain. This study sought to compare and identify associations among these factors in PD patients and controls to elucidate their interrelations and links to clinical manifestations of PD. Methods Stool and plasma samples and clinical data were collected from 55 PD patients and 56 controls. Levels of stool SCFAs and stool and plasma inflammatory and permeability markers were compared between patients and controls and related to one another and to the gut microbiota. Results Calprotectin was increased and SCFAs decreased in stool in PD in a sex-dependent manner. Inflammatory markers in plasma and stool were neither intercorrelated nor strongly associated with SCFA levels. Age at PD onset was positively correlated with SCFAs and negatively correlated with CXCL8 and IL-1β in stool. Fecal zonulin correlated positively with fecal NGAL and negatively with PD motor and non-motor symptoms. Microbiota diversity and composition were linked to levels of SCFAs, inflammatory factors, and zonulin in stool. Certain relationships differed between patients and controls and by sex. Conclusions Intestinal inflammatory responses and reductions in fecal SCFAs occur in PD, are related to the microbiota and to disease onset, and are not reflected in plasma inflammatory profiles. Some of these relationships are distinct in PD and are sex-dependent. This study revealed potential alterations in microbiota-host interactions and links between earlier PD onset and intestinal inflammatory responses and reduced SCFA levels, highlighting candidate molecules and pathways which may contribute to PD pathogenesis and clinical presentation and which warrant further investigation.


2021 ◽  
Author(s):  
Velma T Aho ◽  
Madelyn Crawford Houser ◽  
Pedro AB Pereira ◽  
Jianjun Chang ◽  
Knut Rudi ◽  
...  

Abstract Background Previous studies have reported that gut microbiota, permeability, short-chain fatty acids (SCFAs), and inflammation are altered in Parkinson’s disease (PD), but how these factors are linked and contribute to disease processes and symptoms remains uncertain. This study sought to compare and identify associations among these factors in PD patients and controls to elucidate their interrelations and links to clinical manifestations of PD. Methods Stool and plasma samples and clinical data were collected from 55 PD patients and 56 controls. Levels of stool SCFAs and stool and plasma inflammatory and permeability markers were compared between patients and controls and related to one another and to the gut microbiota. Results Calprotectin was increased and SCFAs decreased in stool in PD in a sex-dependent manner. Inflammatory markers in plasma and stool were neither intercorrelated nor strongly associated with SCFA levels. Age at PD onset was positively correlated with SCFAs and negatively correlated with CXCL8 and IL-1β in stool. Fecal zonulin correlated positively with fecal NGAL and negatively with PD motor and non-motor symptoms. Microbiota diversity and composition were linked to levels of stool SCFAs, inflammation, and zonulin. Certain relationships differed between patients and controls and by sex. Conclusions Intestinal inflammatory responses and reductions in fecal SCFAs occur in PD, are related to the microbiota and to disease onset, and are not reflected in plasma inflammatory profiles. Some of these relationships are PD- and sex-dependent. Alterations in microbiota-host interactions and links between intestinal inflammation and reduced SCFA levels and earlier PD onset warrant further investigation.


2020 ◽  
Author(s):  
Velma T Aho ◽  
Madelyn Crawford Houser ◽  
Pedro AB Pereira ◽  
Jianjun Chang ◽  
Knut Rudi ◽  
...  

Abstract Background: Previous studies have reported that gut microbiota, permeability, short-chain fatty acids (SCFAs), and inflammation are altered in Parkinson’s disease (PD), but how these factors are linked and contribute to disease processes and symptoms remains uncertain. This study sought to compare and identify associations among these factors in PD patients and controls to elucidate their interrelations and links to clinical manifestations of PD.Methods: Stool and plasma samples and clinical data were collected from 55 PD patients and 56 controls. Levels of stool SCFAs and stool and plasma inflammatory and permeability markers were compared between patients and controls and related to one another and to the gut microbiota.Results: Calprotectin was increased and SCFAs decreased in stool in PD in a sex-dependent manner. Inflammatory markers in plasma and stool were neither intercorrelated nor strongly associated with SCFA levels. Age at PD onset was positively correlated with SCFAs and negatively correlated with CXCL8 and IL-1β in stool. Fecal zonulin correlated positively with fecal NGAL and negatively with PD motor and non-motor symptoms. Microbiota diversity and composition were linked to levels of stool SCFAs, inflammation, and zonulin. Certain relationships differed between patients and controls and by sex.Conclusions: Intestinal inflammatory responses and reductions in fecal SCFAs occur in PD, are related to the microbiota and to disease onset, and are not reflected in plasma inflammatory profiles. Some of these relationships are PD- and sex-dependent. Alterations in microbiota-host interactions and links between intestinal inflammation and reduced SCFA levels and earlier PD onset warrant further investigation.


2020 ◽  
Author(s):  
Velma T. E. Aho ◽  
Madelyn C. Houser ◽  
Pedro A. B. Pereira ◽  
Jianjun Chang ◽  
Knut Rudi ◽  
...  

AbstractBackgroundPrevious studies have reported that gut microbiota, permeability, short-chain fatty acids (SCFAs), and inflammation are altered in Parkinson’s disease (PD), but how these factors are linked and contribute to disease processes and symptoms remains uncertain.ObjectivesThis study sought to compare and identify associations among these factors in PD patients and controls to elucidate their interrelations and links to clinical manifestations of PD.MethodsStool and plasma samples and clinical data were collected from 55 PD patients and 56 controls. Levels of stool SCFAs and stool and plasma inflammatory and permeability markers were compared between patients and controls and related to one another and to the gut microbiota.ResultsCalprotectin was increased and SCFAs decreased in stool in PD in a sex-dependent manner. Inflammatory markers in plasma and stool were neither intercorrelated nor strongly associated with SCFA levels. Age at PD onset was positively correlated with SCFAs and negatively correlated with CXCL8 and IL-1β in stool. Fecal zonulin correlated positively with fecal NGAL and negatively with PD motor and non-motor symptoms. Microbiota diversity and composition were linked to levels of stool SCFAs, inflammation, and zonulin. These relationships differed somewhat between patients and controls and by sex.ConclusionsIntestinal inflammatory responses and reductions in fecal SCFAs occur in PD, are related to the microbiota and to disease onset, and are not reflected in plasma inflammatory profiles. Some of these relationships are PD- and sex-dependent. Alterations in microbiota-host interactions and links between intestinal inflammation and reduced SCFA levels and earlier PD onset warrant further investigation.


2020 ◽  
Vol 15 (1) ◽  
pp. 52-56
Author(s):  
Sri Winarti ◽  
Agung Pasetyo

The consumption of prebiotics is known to affect the balance of gut microbiota. The purpose of this study was to explore how a galactomannan-rich effervescent drink can affect the population of Lactobacillus, Bifidobacterium, E. coli, and the concentration of short-chain fatty acids in the cecum of rats. Twenty-eight male Wistar rats (aged 2 months) were divided equally into 7 groups and treated orally each day for 15 days with 2 mL effervescent drinks with increasing levels of prebiotic galactomannan. The dosage of 500 mg galactomannan increased the growth of Lactobacillus spp. and Bifidobacterium spp. with inhibition of the growth of E.coli with increased formation of short-chain fatty acids such as acetate, propionate, and butyrate in the cecum of rats.


2020 ◽  
Vol 21 (8) ◽  
pp. 785-798 ◽  
Author(s):  
Abedin Abdallah ◽  
Evera Elemba ◽  
Qingzhen Zhong ◽  
Zewei Sun

The gastrointestinal tract (GIT) of humans and animals is host to a complex community of different microorganisms whose activities significantly influence host nutrition and health through enhanced metabolic capabilities, protection against pathogens, and regulation of the gastrointestinal development and immune system. New molecular technologies and concepts have revealed distinct interactions between the gut microbiota and dietary amino acids (AAs) especially in relation to AA metabolism and utilization in resident bacteria in the digestive tract, and these interactions may play significant roles in host nutrition and health as well as the efficiency of dietary AA supplementation. After the protein is digested and AAs and peptides are absorbed in the small intestine, significant levels of endogenous and exogenous nitrogenous compounds enter the large intestine through the ileocaecal junction. Once they move in the colonic lumen, these compounds are not markedly absorbed by the large intestinal mucosa, but undergo intense proteolysis by colonic microbiota leading to the release of peptides and AAs and result in the production of numerous bacterial metabolites such as ammonia, amines, short-chain fatty acids (SCFAs), branched-chain fatty acids (BCFAs), hydrogen sulfide, organic acids, and phenols. These metabolites influence various signaling pathways in epithelial cells, regulate the mucosal immune system in the host, and modulate gene expression of bacteria which results in the synthesis of enzymes associated with AA metabolism. This review aims to summarize the current literature relating to how the interactions between dietary amino acids and gut microbiota may promote host nutrition and health.


2020 ◽  
Vol 70 ◽  
pp. 20-22 ◽  
Author(s):  
Daniel Grün ◽  
Valerie C. Zimmer ◽  
Jil Kauffmann ◽  
Jörg Spiegel ◽  
Ulrich Dillmann ◽  
...  

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1427
Author(s):  
Junhui Zhang ◽  
Fengqin Feng ◽  
Minjie Zhao

Glycerol monocaprylate (GMC) is a glycerol derivative of medium-chain fatty acids (MCFAs) and is widely used as a preservative in food processing. However, GMC and its hydrolytic acid (octylic acid) have antibacterial properties that may affect the physiology and intestinal microecology of the human body. Therefore, in this study, the effects of two different dosages of GMC (150 and 1600 mg kg−1) on glucose, lipid metabolism, inflammation, and intestinal microecology of normal diet-fed C57BL/6 mice were comprehensively investigated. The obtained results showed that the level of triglycerides (TGs) in the low-dose group down-regulated significantly, and the anti-inflammatory cytokine interleukin 10 (IL-10) significantly increased, while the pro-inflammatory cytokines monocyte chemotactic protein 1 (MCP-1) and interleukin 1beta (IL-1β) in the high-dose group were significantly decreased. Importantly, GMC promoted the α-diversity of gut microbiota in normal-diet-fed mice, regardless of dosages. Additionally, it was found that the low-dose treatment of GMC significantly increased the abundance of Lactobacillus, while the high-dose treatment of GMC significantly increased the abundance of SCFA-producers such as Clostridiales, Lachnospiraceae, and Ruminococcus. Moreover, the content of short-chain fatty acids (SCFAs) was significantly increased by GMC supplementation. Thus, our research provides a novel insight into the effects of GMC on gut microbiota and physiological characteristics.


Author(s):  
Dominic Salamone ◽  
Angela Albarosa Rivellese ◽  
Claudia Vetrani

AbstractGut microbiota and its metabolites have been shown to influence multiple physiological mechanisms related to human health. Among microbial metabolites, short-chain fatty acids (SCFA) are modulators of different metabolic pathways. On the other hand, several studies suggested that diet might influence gut microbiota composition and activity thus modulating the risk of metabolic disease, i.e. obesity, insulin resistance and type 2 diabetes. Among dietary component, dietary fibre may play a pivotal role by virtue of its prebiotic effect on fibre-fermenting bacteria, that may increase SCFA production. The aim of this review was to summarize and discuss current knowledge on the impact of dietary fibre as modulator of the relationship between glucose metabolism and microbiota composition in humans. More specifically, we analysed evidence from observational studies and randomized nutritional intervention investigating the relationship between gut microbiota, short-chain fatty acids and glucose metabolism. The possible mechanisms behind this association were also discussed.


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