Lactate and short chain fatty acids produced by microbial fermentation downregulate proinflammatory responses in intestinal epithelial cells and myeloid cells

Iraporda, Carolina; Errea, Agustina Juliana; Romanin, David Emmanuel; Cayet, Delphine; Pereyra, Elba N.; Pignataro, Omar Pedro; Sirard, Jean‐Claude; Garrote, Graciela Liliana; Abraham, Analía Graciela; Rumbo, Martı́n

doi:10.1016/j.imbio.2015.06.004

Cited by 225 publications

(169 citation statements)

References 53 publications

Supporting

Mentioning

155

Contrasting

Unclassified

Order By: Relevance

“…Butyrate is a more potent HDACi than propionate, which is more potent than acetate. This ranking parallels the effectiveness of the anti-inflammatory activity of SCFAs395960. Propionate failed to inhibit TNF but not IL-6 and IL-12p40 induced by LPS in BMDMs, which mirrored previous observations obtained with trichostatin A and suberanilohydroxamic acid2944616263.…”

Section: Discussionmentioning

confidence: 63%

Impact of the microbial derived short chain fatty acid propionate on host susceptibility to bacterial and fungal infections in vivo

Ciarlo

Heinonen

Herderscheê

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Short chain fatty acids (SCFAs) produced by intestinal microbes mediate anti-inflammatory effects, but whether they impact on antimicrobial host defenses remains largely unknown. This is of particular concern in light of the attractiveness of developing SCFA-mediated therapies and considering that SCFAs work as inhibitors of histone deacetylases which are known to interfere with host defenses. Here we show that propionate, one of the main SCFAs, dampens the response of innate immune cells to microbial stimulation, inhibiting cytokine and NO production by mouse or human monocytes/macrophages, splenocytes, whole blood and, less efficiently, dendritic cells. In proof of concept studies, propionate neither improved nor worsened morbidity and mortality parameters in models of endotoxemia and infections induced by gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae), gram-positive bacteria (Staphylococcus aureus, Streptococcus pneumoniae) and Candida albicans. Moreover, propionate did not impair the efficacy of passive immunization and natural immunization. Therefore, propionate has no significant impact on host susceptibility to infections and the establishment of protective anti-bacterial responses. These data support the safety of propionate-based therapies, either via direct supplementation or via the diet/microbiota, to treat non-infectious inflammation-related disorders, without increasing the risk of infection.

show abstract

Section: Discussionmentioning

confidence: 63%

Impact of the microbial derived short chain fatty acid propionate on host susceptibility to bacterial and fungal infections in vivo

Ciarlo

Heinonen

Herderscheê

et al. 2016

Sci Rep

View full text Add to dashboard Cite

show abstract

“…But we did not find any effect of 10 mg V/kg on the cecum flora ecology (H, EH, S), which may be because of the feedback regulation cause by SCFA. As produced by microbial fermentation, SCFA downregulate proinflammatory responses to protect intestinal epithelial cells apoptosis [48]. Butyrate acid provides energy to cells [49] and is also related with epithelial cells apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Effect of Vanadium and Tea Polyphenols on Intestinal Morphology, Microflora and Short-Chain Fatty Acid Profile of Laying Hens

Yuan

Wang

Zhang

et al. 2016

Biol Trace Elem Res

View full text Add to dashboard Cite

Vanadium (V) is a trace element which can induce dysfunction of gastro-intestine and egg quality deterioration of laying hens. This study was conducted to determine the effect of tea polyphenols (TP) on intestinal morphology, microflora, and short-chain fatty acid (SCFA) profile of laying hens fed vanadium containing diets. A total of 120 Lohman laying hens (67-week-old) were randomly divided into 4 groups with 6 replicates and 5 birds each for a 35-day feeding trial. The dietary treatments were as follows: (1) control (CON), fed a basal diet; (2) vanadium treatment (V10), CON +10 mg V/kg; (3) TP treatment 1 (TP1): V10 + 600 mg TP/kg; (4) TP treatment 2 (TP2): V10 + 1000 mg TP/kg. Fed 10 mg V/kg diets to laying hens did not affect the cecum flora diversity index (H), degree of homogeneity (EH), and richness (S), but hens fed TP2 diet decreased the H, EH, and S (P < 0.05). The cecum butyrate acid concentration was lower in V10 treatment and higher in TP2 treatment (P < 0.05). Addition of 10 mg/kg V resulted in an increased (P < 0.01) duodenal cell apoptosis rate, and 1000 mg/kg TP supplementation overcame (P < 0.01) this reduction effect induced by vanadium. The results indicated that supplementation of 10 mg/kg vanadium increased duodenal cell apoptosis and reduced cecum butyrate acid content. Addition of 1000 mg/kg TP increased the SCFA production to affect cecum flora ecology and protected the duodenal cell from excess apoptosis caused by vanadium.

show abstract

“…Abrogation of TLR4 signalling or suppression of intestinal microbiota with antibiotics was protective against both macrophage activation and liver injury in these models 180,181 . Similarly, there is evidence that the pathogenesis of NAFLD and NASH involves activation of hepatic macrophages 187 that might begin with in utero exposures to lipid overload or fetal hypoxia as one critical pathway, and potentially by gutderived or metabolic factors other than fat, such as succinate 159 or SCFAs 188 , as another critical pathway (FIG. 3).…”

Section: Hepatic Macrophages and Nafldmentioning

confidence: 99%

Developmental origins of NAFLD: a womb with a clue

Wesolowski

Kasmi

Jonscher

et al. 2016

Nat Rev Gastroenterol Hepatol

168

167

View full text Add to dashboard Cite

Changes in the maternal environment leading to an altered intrauterine milieu can result in subtle insults to the fetus, promoting increased lifetime disease risk and/or disease acceleration in childhood and later in life. Particularly worrisome is that the prevalence of NAFLD is rapidly increasing among children and adults, and is being diagnosed at increasingly younger ages, pointing towards an early-life origin. A wealth of evidence, in humans and non-human primates, suggests that maternal nutrition affects the placenta and fetal tissues, leading to persistent changes in hepatic metabolism, mitochondrial function, the intestinal microbiota, liver macrophage activation and susceptibility to NASH postnatally. Deleterious exposures in utero include fetal hypoxia, increased nutrient supply, inflammation and altered gut microbiota that might produce metabolic clues, including fatty acids, metabolites, endotoxins, bile acids and cytokines, which prime the infant liver for NAFLD in a persistent manner and increase susceptibility to NASH. Mechanistic links to early disease pathways might involve shifts in lipid metabolism, mitochondrial dysfunction, pioneering gut microorganisms, macrophage programming and epigenetic changes that alter the liver microenvironment, favouring liver injury. In this Review, we discuss how maternal, fetal, neonatal and infant exposures provide developmental clues and mechanisms to help explain NAFLD acceleration and increased disease prevalence. Mechanisms identified in clinical and preclinical models suggest important opportunities for prevention and intervention that could slow down the growing epidemic of NAFLD in the next generation.NAFLD is a general term used to describe a broad spectrum of liver abnormalities, ranging from simple, uncomplicated hepatic steatosis to NASH, accompanied by different degrees of Correspondence to J.E.F. jed.friedman@ucdenver.edu. Author contributionsAll authors researched data for the article, provided a substantial contribution to discussion of content, wrote the article, and reviewed and edited the manuscript before submission. Competing interests statementThe authors declare no competing interests. HHS Public AccessAuthor manuscript Nat Rev Gastroenterol Hepatol. Author manuscript; available in PMC 2017 December 12. Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript inflammation and fibrosis. NAFLD is increasing in prevalence, especially in adolescents 1 , despite the levellingoff of the obesity epidemic from 2003-2004 to 2013-2014 in children and adolescents aged 2-19 years (REF.2). The most common chronic liver disease worldwide, NAFLD increases the risk of cardiovascular events eightfold and type 2 diabetes mellitus (T2DM) threefold 3 , and is a strong risk factor for hepatocellular carcinoma (HCC) 4 . At the time of paediatric NAFLD diagnosis, 25-50% of children have NASH and 10-25% have advanced fibrosis 5 . For many decades, it was thought that NAFLD was predominantly driven by obesity in the setting of genetic suscep...

show abstract

Lactate and short chain fatty acids produced by microbial fermentation downregulate proinflammatory responses in intestinal epithelial cells and myeloid cells

Cited by 225 publications

References 53 publications

Impact of the microbial derived short chain fatty acid propionate on host susceptibility to bacterial and fungal infections in vivo

Impact of the microbial derived short chain fatty acid propionate on host susceptibility to bacterial and fungal infections in vivo

Effect of Vanadium and Tea Polyphenols on Intestinal Morphology, Microflora and Short-Chain Fatty Acid Profile of Laying Hens

Developmental origins of NAFLD: a womb with a clue

Contact Info

Product

Resources

About