Short-Chain Fatty Acids Prevent Diabetic Nephropathy In Vivo and In Vitro

AbstractShort-chain fatty acids (SCFAs) are metabolites produced in the gut via microbial fermentation of dietary fibers referred to as microbiota-accessible carbohydrates (MACs). Acetate, propionate, and butyrate have been observed to regulate host dietary nutrient metabolism, energy balance, and local and systemic immune functions. In vitro and in vivo experiments have shown links between the presence of bacteria-derived SCFAs and host health through the blunting of inflammatory processes, as well as purported protection from the development of illness associated with respiratory infections. This bank of evidence suggests that SCFAs could be beneficial to enhance the athlete’s immunity, as well as act to improve exercise recovery via anti-inflammatory activity and to provide additional energy substrates for exercise performance. However, the mechanistic basis and applied evidence for these relationships in humans have yet to be fully established. In this narrative review, we explore the existing knowledge of SCFA synthesis and the functional importance of the gut microbiome composition to induce SCFA production. Further, changes in gut microbiota associated with exercise and various dietary MACs are described. Finally, we provide suggestions for future research and practical applications, including how these metabolites could be manipulated through dietary fiber intake to optimize immunity and energy metabolism.

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Studies on lipid digestion in the preruminant calf

British Journal Of Nutrition ◽

10.1079/bjn19780102 ◽

1978 ◽

Vol 40 (1) ◽

pp. 125-131 ◽

Cited By ~ 10

Author(s):

J. D. Edwards-Webb ◽

S. Y. Thompson

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Free Fatty Acids ◽

Butyric Acid ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Esterified Fatty Acids ◽

Chain Fatty Acids

1. The lipolysis of cow's milk fat by salivary lipase (EC 3.1.1.3) in the preruminant calf has been studied in vitro by a simulated abomasal digestion, and also in vivo by examining the abomasal effluent collected over 12 h after giving whole milk to a calf.2. In the in vitro experiment the liquid drained from the clot contained a higher proportion of short-chain fatty acids than the abomasal effluent in the in vivo experiment. This was considered to indicate the absorption of short-chain free fatty acids from within the abomasum.3. Preferential release of short-chain fatty acids both in vitro and in vivo was observed.4. The outflow of butyric acid from the abomasum of the calf was initially rapid, but had levelled off at approximately 6 h, whereas the outflow of a typical long-chain fatty acid (palmitic) was fairly constant over the 12 h.Butyric acid predominated in the free fatty acids of abomasal effluent 0.5 h after feeding (668 mmol/mol total free fatty acids) but had become a minor component by 12 h (15 mmol/mol total free fatty acids).5. The mean amounts of free and esterified fatty acids (mmol/mol fatty acid ingested) present in the abomasal effluent from the 12 h collection period were: triglyceride 465, diglyceride 215, monoglyceride 68, free fatty acid 252. These values showed that only one-third of esterified fatty acids ingested are lipolysed to absorbable products by salivary lipase.

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Production, Structural Characterization, and In Vitro Assessment of the Prebiotic Potential of Butyl-Fructooligosaccharides

International Journal of Molecular Sciences ◽

10.3390/ijms21020445 ◽

2020 ◽

Vol 21 (2) ◽

pp. 445 ◽

Cited By ~ 2

Author(s):

Sini Kang ◽

Hyun Ju You ◽

Yeong-Geun Lee ◽

Yunju Jeong ◽

Tony V. Johnston ◽

...

Keyword(s):

Fatty Acids ◽

Short Chain Fatty Acids ◽

Fecal Microbiota ◽

Negative Control ◽

Short Chain ◽

Control Group ◽

Metabolic Genes ◽

Chain Fatty Acids

Short-chain fatty acids (SCFAs), especially butyrate, produced in mammalian intestinal tracts via fermentation of dietary fiber, are known biofunctional compounds in humans. However, the variability of fermentable fiber consumed on a daily basis and the diversity of gut microbiota within individuals often limits the production of short-chain fatty acids in the human gut. In this study, we attempted to enhance the butyrate levels in human fecal samples by utilizing butyl-fructooligosaccharides (B-FOS) as a novel prebiotic substance. Two major types of B-FOS (GF3-1B and GF3-2B), composed of short-chain fructooligosaccharides (FOS) bound to one or two butyric groups by ester bonds, were synthesized. Qualitative analysis of these B-FOS using Fourier transform infrared (FT-IR) spectroscopy, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), nuclear magnetic resonance (NMR) and low-resolution fast-atom bombardment mass spectra (LR-FAB-MS), showed that the chemical structure of GF3-1B and GF3-2B were [O-(1-buty-β-D-fru-(2→1)-O-β-D-fru-(2→1)-O-β-D-fru-O-α-D-glu] and [O-(1-buty)-β-D-fru-(2→1)-O-β-D-fru-(2→1)-O-(4-buty)-β-D-fru-O-α-D-glu], respectively. The ratio of these two compounds was approximately 5:3. To verify their biofunctionality as prebiotic oligosaccharides, proliferation and survival patterns of human fecal microbiota were examined in vitro via 16S rRNA metagenomics analysis compared to a positive FOS control and a negative control without a carbon source. B-FOS treatment showed different enrichment patterns on the fecal microbiota community during fermentation, and especially stimulated the growth of major butyrate producing bacterial consortia and modulated specific butyrate producing pathways with significantly enhanced butyrate levels. Furthermore, the relative abundance of Fusobacterium and ammonia production with related metabolic genes were greatly reduced with B-FOS and FOS treatment compared to the control group. These findings indicate that B-FOS differentially promotes butyrate production through the enhancement of butyrate-producing bacteria and their metabolic genes, and can be applied as a novel prebiotic compound in vivo.

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Influence of diet on growth yields of rumen micro-organisms in vitro andin vivo: influence on growth yield of variable carbon fluxes to fermentation products

British Journal Of Nutrition ◽

10.1079/bjn2003934 ◽

2003 ◽

Vol 90 (3) ◽

pp. 625-634 ◽

Cited By ~ 41

Author(s):

M. Blümmel ◽

A. Karsli ◽

J. R. Russell

Keyword(s):

Fatty Acids ◽

Microbial Biomass ◽

Short Chain Fatty Acids ◽

Gas Production ◽

Microbial Production ◽

Short Chain ◽

Maize Grain ◽

Chain Fatty Acids

The efficiency of rumen microbial production (EMP)in vitroandin vivowas examined for three roughages (lucerne (Medicago sativaL.) hay, oat (Avenia sativaL.)–berseem clover (Trifolium alexandrinumcultivar BigBee) hay and maize (Zea maysL.) crop residue (MCR)) and for five isonitrogenous (106 g crude protein (N × 6·25)/kg) diets formulated from lucerne hay, oat–berseem clover hay, MCR, soya-bean meal and maize grain to provide degradable intake protein for the production of 130 g microbial protein/kg total digestible nutrients. EMPin vivowas determined by intestinal purine recovery in sheep and ranged from 240 to 360 g microbial biomass/kg organic matter truly degraded in MCR and in one of the diets respectively (P<0·05). EMPin vitrowas estimated by the substrate degraded: gas volume produced thereby (termed partitioning factor, PF (mg/ml)) at times of estimated peak microbial production and after 16·0 and 24·0h of incubation. For the diets, PF values were significantly related to EMPin vivoat peak microbial production (P= 0·04), but not after 16·0 (P= 0·08) and 24·0h (P= 0·66). For roughages, PF values were significantly related to EMPin vivoonly when measured after 16·0 h (P= 0·04). For MCR and diets, a close non-linear relationship was found between PF values at peak microbial production and EMPin vivo(R20·99,P<0·0001) suggesting a maximum EMPin vivoof 0·39. Low gas production per unit substrate degraded (high PF) was associated with high EMPin vivo.Thein vitrostudy of the products of fermentation, short-chain fatty acids, gases and microbial biomass (by purine analysis) after 16·0h of incubation showed very strong relationships (R2≥ 0·89,P<0·0001) between short-chain fatty acids, gases and gravimetrically measured apparent degradability. Except for maize grain, the true degradability of organic matter estimated by neutral-detergent solution treatment agreed with the sum of the products of fermentation (R20·81,P=0·0004). After 16·0h of incubation, the synergistic effects of diet ingredient on diets were greater for microbial biomass (18%) than for short-chain fatty acids and gas production (7 %). It is concluded that measurement of gas production only gives incomplete information about fodder quality; complementation of gas measurements by true degradability measurements is recommended.

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Molecular analysis of the effect of short-chain fatty acids on intestinal cell proliferation

Proceedings of The Nutrition Society ◽

10.1079/pns2002215 ◽

2003 ◽

Vol 62 (1) ◽

pp. 101-106 ◽

Cited By ~ 130

Author(s):

Herve M. Blottiere ◽

Bruno Buecher ◽

Jean-Paul Galmiche ◽

Christine Cherbut

Keyword(s):

Fatty Acids ◽

Cell Proliferation ◽

Short Chain Fatty Acids ◽

Cyclin D3 ◽

Short Chain ◽

Intestinal Cell ◽

Inhibitory Protein ◽

Chain Fatty Acids

Short-chain fatty acids (SCFA), particularly butyrate, were shown to regulate cell proliferation in vitro and in vivo. Indeed, butyrate is the major fuel for colonic epithelial cells, and it can influence cell proliferation through the release of growth factors or gastrointestinal peptides such as gastrin, or through modulation of mucosal blood flow. Lastly, SCFA can act directly on genes regulating cell proliferation, and butyrate is the main SCFA to display such an effect. Butyrate inhibits histone deacetylase, which will allow histone hyperacetylation. Such hyperacetylation leads to transcription of several genes, including p21/Cipl. Moreover, it will allow cyclin D3 hyper-expression by inhibiting its degradation. The induction of the cyclin-dependent kinase inhibitory protein p21/Cipl accounts for cell arrest in the Gl phase of the cell cycle. However, in the absence of p21 other mechanisms are initiated, leading to inhibition of cell proliferation.

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Postnatal development of the myenteric glial network and its modulation by butyrate

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00232.2015 ◽

2016 ◽

Vol 310 (11) ◽

pp. G941-G951 ◽

Cited By ~ 16

Author(s):

François Cossais ◽

Tony Durand ◽

Julien Chevalier ◽

Marie Boudaud ◽

Laetitia Kermarrec ◽

...

Keyword(s):

Fatty Acids ◽

Short Chain Fatty Acids ◽

Enteric Neurons ◽

Short Chain ◽

Postnatal Maturation ◽

Enteric Glial Cells ◽

Postnatal Evolution ◽

Chain Fatty Acids

The postnatal period is crucial for the development of gastrointestinal (GI) functions. The enteric nervous system is a key regulator of GI functions, and increasing evidences indicate that 1) postnatal maturation of enteric neurons affect the development of GI functions, and 2) microbiota-derived short-chain fatty acids can be involved in this maturation. Although enteric glial cells (EGC) are central regulators of GI functions, the postnatal evolution of their phenotype remains poorly defined. We thus characterized the postnatal evolution of EGC phenotype in the colon of rat pups and studied the effect of short-chain fatty acids on their maturation. We showed an increased expression of the glial markers GFAP and S100β during the first postnatal week. As demonstrated by immunohistochemistry, a structured myenteric glial network was observed at 36 days in the rat colons. Butyrate inhibited EGC proliferation in vivo and in vitro but had no effect on glial marker expression. These results indicate that the EGC myenteric network continues to develop after birth, and luminal factors such as butyrate endogenously produced in the colon may affect this development.

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Short-chain fatty acids stimulate the migration of neutrophils to inflammatory sites

Clinical Science ◽

10.1042/cs20080642 ◽

2009 ◽

Vol 117 (9) ◽

pp. 331-338 ◽

Cited By ~ 76

Author(s):

Marco A. R. Vinolo ◽

Hosana G. Rodrigues ◽

Elaine Hatanaka ◽

Cristina B. Hebeda ◽

Sandra H. P. Farsky ◽

...

Keyword(s):

Fatty Acids ◽

Neutrophil Migration ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Mrna Levels ◽

Air Pouch ◽

Β2 Integrin ◽

Chain Fatty Acids

SCFAs (short-chain fatty acids) are produced by anaerobic bacterial fermentation. Increased concentrations of these fatty acids are observed in inflammatory conditions, such as periodontal disease, and at sites of anaerobic infection. In the present study, the effect of the SCFAs acetate, propionate and butyrate on neutrophil chemotaxis and migration was investigated. Experiments were carried out in rats and in vitro. The following parameters were measured: rolling, adherence, expression of adhesion molecules in neutrophils (L-selectin and β2 integrin), transmigration, air pouch influx of neutrophils and production of cytokines [CINC-2αβ (cytokine-induced neutrophil chemoattractant-2αβ), IL-1β (interleukin-1β), MIP-1α (macrophage inflammatory protein-1α) and TNF-α (tumour necrosis factor-α)]. SCFAs induced in vivo neutrophil migration and increased the release of CINC-2αβ into the air pouch. These fatty acids increased the number of rolling and adhered cells as evaluated by intravital microscopy. SCFA treatment increased L-selectin expression on the neutrophil surface and L-selectin mRNA levels, but had no effect on the expression of β2 integrin. Propionate and butyrate also increased in vitro transmigration of neutrophils. These results indicate that SCFAs produced by anaerobic bacteria raise neutrophil migration through increased L-selectin expression on neutrophils and CINC-2αβ release.

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Inhibitory Effects of Pulse Bioactive Compounds on Cancer Development Pathways

Diseases ◽

10.3390/diseases6030072 ◽

2018 ◽

Vol 6 (3) ◽

pp. 72 ◽

Cited By ~ 8

Author(s):

Shiwangni Rao ◽

Kenneth Chinkwo ◽

Abishek Santhakumar ◽

Christopher Blanchard

Keyword(s):

Fatty Acids ◽

Bioactive Compounds ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Cancer Development ◽

In Vivo Studies ◽

Culture Models ◽

Chain Fatty Acids

Previous studies suggest that pulses may have the potential to protect against cancer development by inhibiting pathways that result in the development of cancer. These pathways include those that result in inflammation, DNA damage, cell proliferation, and metastasis. Other studies have demonstrated extracts from pulses have the capacity to induce apoptosis specifically in cancer cells. Compounds reported to be responsible for these activities have included phenolic compounds, proteins and short chain fatty acids. The majority of the studies have been undertaken using in vitro cell culture models, however, there are a small number of in vivo studies that support the hypothesis that pulse consumption may inhibit cancer development. This review highlights the potential benefit of a diet rich in pulse bioactive compounds by exploring the anti-cancer properties of its polyphenols, proteins and short chain fatty acids.

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Antibiotic-induced decreases in the levels of microbial-derived short-chain fatty acids promote gastrointestinal colonization ofCandida albicans

10.1101/428474 ◽

2018 ◽

Author(s):

Jack Guinan ◽

Shaohua Wang ◽

Hariom Yadav ◽

Shankar Thangamani

Keyword(s):

Fatty Acids ◽

Significant Risk ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Ofcandida Albicans ◽

Biofilm Development ◽

Gastrointestinal Colonization ◽

Chain Fatty Acids

ABSTRACTCandida albicansis the fourth most common cause of systemic nosocomial infections, posing a significant risk in immunocompromised individuals. As the majority of systemicC. albicansinfections stem from endogenous gastrointestinal (GI) colonization, understanding the mechanisms associated with GI colonization is essential in the development of novel methods to preventC. albicans-related mortality. In this study, we investigated the role of microbial-derived short-chain fatty acids (SCFAs) including acetate, butyrate, and propionate on growth, morphogenesis, and GI colonization ofC. albicans. Our results indicate that cefoperazone-treated mice susceptible toC. albicansinfection had significantly decreased levels of SCFAs in the cecal contents that correlate with a higher fungal load in the feces. Further, usingin vivoconcentration of SCFAs, we demonstrated that SCFAs inhibit the growth, germ tube, hyphae and biofilm development ofC. albicans in vitro. Collectively, results from this study demonstrate that antibiotic-induced decreases in the levels of SCFAs in the cecum enhances the growth and GI colonization ofC. albicans.

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β-Glucan-Induced Immuno-Modulation: A Role for the Intestinal Microbiota and Short-Chain Fatty Acids in Common Carp

Frontiers in Immunology ◽

10.3389/fimmu.2021.761820 ◽

2022 ◽

Vol 12 ◽

Author(s):

Jules Petit ◽

Irene de Bruijn ◽

Mark R. G. Goldman ◽

Erik van den Brink ◽

Wilbert F. Pellikaan ◽

...

Keyword(s):

Fatty Acids ◽

Common Carp ◽

Intestinal Microbiota ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Type I ◽

Immunomodulatory Effects ◽

Chain Fatty Acids

Dietary supplementation of fish with β-glucans has been commonly associated with immunomodulation and generally accepted as beneficial for fish health. However, to date the exact mechanisms of immunomodulation by β-glucan supplementation in fish have remained elusive. In mammals, a clear relation between high-fibre diets, such as those including β-glucans, and diet-induced immunomodulation via intestinal microbiota and associated metabolites has been observed. In this study, first we describe by 16S rRNA sequencing the active naive microbiota of common carp intestine. Based on the abundance of the genus Bacteroides, well known for their capacity to degrade and ferment carbohydrates, we hypothesize that common carp intestinal microbiota could ferment dietary β-glucans. Indeed, two different β-glucan preparations (curdlan and MacroGard®) were both fermented in vitro, albeit with distinct fermentation dynamics and distinct production of short-chain fatty acids (SCFA). Second, we describe the potential immunomodulatory effects of the three dominant SCFAs (acetate, butyrate, and propionate) on head kidney leukocytes, showing effects on both nitric oxide production and expression of several cytokines (il-1b, il-6, tnfα, and il-10) in vitro. Interestingly, we also observed a regulation of expression of several gpr40L genes, which were recently described as putative SCFA receptors. Third, we describe how a single in vivo oral gavage of carp with MacroGard® modulated simultaneously, the expression of several pro-inflammatory genes (il-1b, il-6, tnfα), type I IFN-associated genes (tlr3.1, mx3), and three specific gpr40L genes. The in vivo observations provide indirect support to our in vitro data and the possible role of SCFAs in β-glucan-induced immunomodulation. We discuss how β-glucan-induced immunomodulatory effects can be explained, at least in part, by fermentation of MacroGard® by specific bacteria, part of the naive microbiota of common carp intestine, and how a subsequent production of SFCAs could possibly explain immunomodulation by β-glucan via SCFA receptors present on leukocytes.

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