Short-chain fatty acids (SCFAs) are fatty acids of two to six carbon atoms. [1] The SCFAs' lower limit is interpreted differently, either with one, two, three or four carbon atoms.[ citation needed ] Derived from intestinal microbial fermentation of indigestible foods, SCFAs in human gut are acetic, propionic and butyric acid. They are the main energy source of colonocytes, making them crucial to gastrointestinal health. [1] [2] SCFAs all possess varying degrees of water solubility, which distinguishes them from longer chain fatty acids that are immiscible.
Lipid number | Name | Salt/Ester Name | Formula | Mass (g/mol) | Diagram | |||
---|---|---|---|---|---|---|---|---|
Common | Systematic | Common | Systematic | Molecular | Structural | |||
C2:0 | Acetic acid | Ethanoic acid | Acetate | Ethanoate | C 2 H 4 O 2 | CH3COOH | 60.05 | |
C3:0 | Propionic acid | Propanoic acid | Propionate | Propanoate | C 3 H 6 O 2 | CH3CH2COOH | 74.08 | |
C4:0 | Butyric acid | Butanoic acid | Butyrate | Butanoate | C 4 H 8 O 2 | CH3(CH2)2COOH | 88.11 | |
C4:0 | Isobutyric acid | 2-Methylpropanoic acid | Isobutyrate | 2-Methylpropanoate | C 4 H 8 O 2 | (CH3)2CHCOOH | 88.11 | |
C5:0 | Valeric acid | Pentanoic acid | Valerate | Pentanoate | C 5 H 10 O 2 | CH3(CH2)3COOH | 102.13 | |
C5:0 | Isovaleric acid | 3-Methylbutanoic acid | Isovalerate | 3-Methylbutanoate | C 5 H 10 O 2 | (CH3)2CHCH2COOH | 102.13 | |
C5:0 | 2-Methylbutyric acid | 2-Methylbutyric acid | 2-Methylbutanoate | 2-Methylbutanoate | C 5 H 10 O 2 | CH3CH2CH(CH3)COOH | 102.13 |
SCFAs are produced when dietary fiber is fermented in the colon. [1] [3] Macronutrient composition (carbohydrate, protein or fat) of diets affects circulating SCFAs. [4]
Acetate, propionate and butyrate are the three most common SCFAs. [3]
SCFAs and medium-chain fatty acids are primarily absorbed through the portal vein during lipid digestion, [5] while long-chain fatty acids are packed into chylomicrons, enter lymphatic capillaries, then transfer to the blood at the subclavian vein. [1]
SCFAs have diverse physiological roles in body functions. [1] [2] They can affect the production of lipids, energy and vitamins. [6] They can also affect appetite and cardiometabolic health. [4] Additionally they may have an impact on mental health and mood. [7] The three main SCFAs, acetate, propionate and butyrate, were shown to lower blood pressure in experimental models, [8] [9] [10] [11] and clinical trials to determine their effect on hypertensive patients are underway. [12] Butyrate is particularly important for colon health because it is the primary energy source for colonocytes (the epithelial cells of the colon). [1] [2] The liver can use acetate for energy. [13]
In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, from 4 to 28. Fatty acids are a major component of the lipids in some species such as microalgae but in some other organisms are not found in their standalone form, but instead exist as three main classes of esters: triglycerides, phospholipids, and cholesteryl esters. In any of these forms, fatty acids are both important dietary sources of fuel for animals and important structural components for cells.
Dietary fiber or roughage is the portion of plant-derived food that cannot be completely broken down by human digestive enzymes. Dietary fibers are diverse in chemical composition, and can be grouped generally by their solubility, viscosity, and fermentability, which affect how fibers are processed in the body. Dietary fiber has two main components: soluble fiber and insoluble fiber, which are components of plant-based foods, such as legumes, whole grains and cereals, vegetables, fruits, and nuts or seeds. A diet high in regular fiber consumption is generally associated with supporting health and lowering the risk of several diseases. Dietary fiber consists of non-starch polysaccharides and other plant components such as cellulose, resistant starch, resistant dextrins, inulin, lignins, chitins, pectins, beta-glucans, and oligosaccharides.
A nutrient is a substance used by an organism to survive, grow, and reproduce. The requirement for dietary nutrient intake applies to animals, plants, fungi, and protists. Nutrients can be incorporated into cells for metabolic purposes or excreted by cells to create non-cellular structures, such as hair, scales, feathers, or exoskeletons. Some nutrients can be metabolically converted to smaller molecules in the process of releasing energy, such as for carbohydrates, lipids, proteins, and fermentation products, leading to end-products of water and carbon dioxide. All organisms require water. Essential nutrients for animals are the energy sources, some of the amino acids that are combined to create proteins, a subset of fatty acids, vitamins and certain minerals. Plants require more diverse minerals absorbed through roots, plus carbon dioxide and oxygen absorbed through leaves. Fungi live on dead or living organic matter and meet nutrient needs from their host.
Butyric acid, also known under the systematic name butanoic acid, is a straight-chain alkyl carboxylic acid with the chemical formula CH3CH2CH2CO2H. It is an oily, colorless liquid with an unpleasant odor. Isobutyric acid is an isomer. Salts and esters of butyric acid are known as butyrates or butanoates. The acid does not occur widely in nature, but its esters are widespread. It is a common industrial chemical and an important component in the mammalian gut.
Propionic acid is a naturally occurring carboxylic acid with chemical formula CH
3CH
2CO
2H. It is a liquid with a pungent and unpleasant smell somewhat resembling body odor. The anion CH
3CH
2CO−
2 as well as the salts and esters of propionic acid are known as propionates or propanoates.
The rumen, also known as a paunch, is the largest stomach compartment in ruminants and the larger part of the reticulorumen, which is the first chamber in the alimentary canal of ruminant animals. The rumen's microbial favoring environment allows it to serve as the primary site for microbial fermentation of ingested feed. The smaller part of the reticulorumen is the reticulum, which is fully continuous with the rumen, but differs from it with regard to the texture of its lining.
Gut microbiota, gut microbiome, or gut flora are the microorganisms, including bacteria, archaea, fungi, and viruses, that live in the digestive tracts of animals. The gastrointestinal metagenome is the aggregate of all the genomes of the gut microbiota. The gut is the main location of the human microbiome. The gut microbiota has broad impacts, including effects on colonization, resistance to pathogens, maintaining the intestinal epithelium, metabolizing dietary and pharmaceutical compounds, controlling immune function, and even behavior through the gut–brain axis.
Resistant starch (RS) is starch, including its degradation products, that escapes from digestion in the small intestine of healthy individuals. Resistant starch occurs naturally in foods, but it can also be added as part of dried raw foods, or used as an additive in manufactured foods.
Calcium propanoate or calcium propionate has the formula Ca(C2H5COO)2. It is the calcium salt of propanoic acid.
In biology, syntrophy, syntrophism, or cross-feeding is the cooperative interaction between at least two microbial species to degrade a single substrate. This type of biological interaction typically involves the transfer of one or more metabolic intermediates between two or more metabolically diverse microbial species living in close proximity to each other. Thus, syntrophy can be considered an obligatory interdependency and a mutualistic metabolism between different microbial species, wherein the growth of one partner depends on the nutrients, growth factors, or substrates provided by the other(s).
Free fatty acid receptors (FFARs) are G-protein coupled receptors (GPRs). GPRs are a large family of receptors. They reside on their parent cells' surface membranes, bind any one of a specific set of ligands that they recognize, and thereby are activated to elicit certain types of responses in their parent cells. Humans express more than 800 different types of GPCRs. FFARs are GPCR that bind and thereby become activated by particular fatty acids. In general, these binding/activating fatty acids are straight-chain fatty acids consisting of a carboxylic acid residue, i.e., -COOH, attached to aliphatic chains, i.e. carbon atom chains of varying lengths with each carbon being bound to 1, 2 or 3 hydrogens. For example, propionic acid is a short-chain fatty acid consisting of 3 carbons (C's), CH3-CH2-COOH, and docosahexaenoic acid is a very long-chain polyunsaturated fatty acid consisting of 22 C's and six double bonds : CH3-CH2-CH1=CH1-CH2-CH1=CH1-CH2-CH1=CH1-CH2-CH1=CH1-CH2-CH1=CH1-CH2-CH1=CH1-CH2-CH2-COOH.
Free fatty acid receptor 3 protein is a G protein coupled receptor that in humans is encoded by the FFAR3 gene. GPRs reside on cell surfaces, bind specific signaling molecules, and thereby are activated to trigger certain functional responses in their parent cells. FFAR3 is a member of the free fatty acid receptor group of GPRs that includes FFAR1, FFAR2, and FFAR4. All of these FFARs are activated by fatty acids. FFAR3 and FFAR2 are activated by certain short-chain fatty acids (SC-FAs), i.e., fatty acids consisting of 2 to 6 carbon atoms whereas FFFAR1 and FFAR4 are activated by certain fatty acids that are 6 to more than 21 carbon atoms long. Hydroxycarboxylic acid receptor 2 is also activated by a SC-FA that activate FFAR3, i.e., butyric acid.
Free fatty acid receptor 2 (FFAR2), also termed G-protein coupled receptor 43 (GPR43), is a rhodopsin-like G-protein coupled receptor. It is coded by the FFAR2 gene. In humans, the FFAR2 gene is located on the long arm of chromosome 19 at position 13.12. Like other GPCRs, FFAR2s reside on the surface membrane of cells and when bond to one of their activating ligands regulate the function of their parent cells. FFAR2 is a member of a small family of structurally and functionally related GPRs termed free fatty acid receptors (FFARs). This family includes three other receptors which, like FFAR2, are activated by certain fatty acids: FFAR1, FFAR3 (GPR41), and FFAR4 (GPR120). FFAR2 and FFAR3 are activated by short-chain fatty acids whereas FFAR1 and FFAR4 are activated by long-chain fatty acids.
Long-term close-knit interactions between symbiotic microbes and their host can alter host immune system responses to other microorganisms, including pathogens, and are required to maintain proper homeostasis. The immune system is a host defense system consisting of anatomical physical barriers as well as physiological and cellular responses, which protect the host against harmful microorganisms while limiting host responses to harmless symbionts. Humans are home to 1013 to 1014 bacteria, roughly equivalent to the number of human cells, and while these bacteria can be pathogenic to their host most of them are mutually beneficial to both the host and bacteria.
In molecular biology, acetate kinase (EC 2.7.2.1), which is predominantly found in micro-organisms, facilitates the production of acetyl-CoA by phosphorylating acetate in the presence of ATP and a divalent cation. Short-chain fatty acids (SCFAs) play a major role in carbon cycle and can be utilized as a source of carbon and energy by bacteria. Salmonella typhimurium propionate kinase (StTdcD) catalyzes reversible transfer of the γ-phosphate of ATP to propionate during l-threonine degradation to propionate. Kinetic analysis revealed that StTdcD possesses broad ligand specificity and could be activated by various SCFAs (propionate>acetate≈butyrate), nucleotides (ATP≈GTP>CTP≈TTP; dATP>dGTP>dCTP) and metal ions (Mg2+≈Mn2+>Co2+). Inhibition of StTdcD by tricarboxylic acid (TCA) cycle intermediates such as citrate, succinate, α-ketoglutarate and malate suggests that the enzyme could be under plausible feedback regulation. Crystal structures of StTdcD bound to PO4 (phosphate), AMP, ATP, Ap4 (adenosine tetraphosphate), GMP, GDP, GTP, CMP and CTP revealed that binding of nucleotide mainly involves hydrophobic interactions with the base moiety and could account for the broad biochemical specificity observed between the enzyme and nucleotides. Modelling and site-directed mutagenesis studies suggest Ala88 to be an important residue involved in determining the rate of catalysis with SCFA substrates. Molecular dynamics simulations on monomeric and dimeric forms of StTdcD revealed plausible open and closed states, and also suggested role for dimerization in stabilizing segment 235-290 involved in interfacial interactions and ligand binding. Observation of an ethylene glycol molecule bound sufficiently close to the γ-phosphate in StTdcD complexes with triphosphate nucleotides supports direct in-line phosphoryl transfer. The enzyme is important in the process of glycolysis, enzyme levels being increased in the presence of excess glucose. The growth of a bacterial mutant lacking acetate kinase has been shown to be inhibited by glucose, suggesting that the enzyme is involved in excretion of excess carbohydrate. A related enzyme, butyrate kinase, facilitates the formation of butyryl-CoA by phosphorylating butyrate in the presence of ATP to form butyryl phosphate.
The gut–brain axis is the two-way biochemical signaling that takes place between the gastrointestinal tract and the central nervous system (CNS). The "microbiota–gut–brain axis" includes the role of gut microbiota in the biochemical signaling events that take place between the GI tract and the CNS. Broadly defined, the gut–brain axis includes the central nervous system, neuroendocrine system, neuroimmune systems, the hypothalamic–pituitary–adrenal axis, sympathetic and parasympathetic arms of the autonomic nervous system, the enteric nervous system, vagus nerve, and the gut microbiota.
Odd-chain fatty acids are those fatty acids that contain an odd number of carbon atoms. In addition to being classified according to their saturation or unsaturation, fatty acids are also classified according to their odd or even numbers of constituent carbon atoms. With respect to natural abundance, most fatty acids are even chain, e.g. palmitic (C16) and stearic (C18). In terms of physical properties, odd and even fatty acids are similar, generally being colorless, soluble in alcohols, and often somewhat oily. The odd-chain fatty acids are biosynthesized and metabolized slightly differently from the even-chained relatives. In addition to the usual C12-C22 long chain fatty acids, some very long chain fatty acids (VLCFAs) are also known. Some of these VLCFAs are also of the odd-chain variety.
The Lachnospiraceae are a family of obligately anaerobic, variably spore-forming bacteria in the order Eubacteriales that ferment diverse plant polysaccharides to short-chain fatty acids and alcohols (ethanol). These bacteria are among the most abundant taxa in the rumen and the human gut microbiota. Members of this family may protect against colon cancer in humans by producing butyric acid. Lachnospiraceae have been found to contribute to diabetes in genetically susceptible (ob/ob) germ-free mice.
Methanogens are a group of microorganisms that produce methane as a byproduct of their metabolism. They play an important role in the digestive system of ruminants. The digestive tract of ruminants contains four major parts: rumen, reticulum, omasum and abomasum. The food with saliva first passes to the rumen for breaking into smaller particles and then moves to the reticulum, where the food is broken into further smaller particles. Any indigestible particles are sent back to the rumen for rechewing. The majority of anaerobic microbes assisting the cellulose breakdown occupy the rumen and initiate the fermentation process. The animal absorbs the fatty acids, vitamins and nutrient content on passing the partially digested food from the rumen to the omasum. This decreases the pH level and initiates the release of enzymes for further breakdown of the food which later passes to the abomasum to absorb remaining nutrients before excretion. This process takes about 9–12 hours.