User:Lilyward/Butyrate fermentation

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Introduction

Butyrate fermentations generally occurs in butyric acid clostridia which can be isolated from many anaerobic environments such as mud, fermented foods and intestinal tracts or feces. Butyric acid clostridia will ferment carbohydrates into butyric acid. Butyrate in humans originates from the anaerobic microbes that ferment dietary fibers in the lower intestinal tract. Butyrate plays an important role in immune and inflammatory responses, as well as the formation of the intestinal barrier. The presence of short-chain fatty acids lowers the pH of the gut allowing optimal growth for butyrate-producing bacteria. The two major metabolic pathways for butyrate fermentation are butyryl-CoA phosphorylation and acetate CoA transferase further described in the Microbial Biosynthesis section below.

Microbial Biosynthesis

One pathway for butyrate biosynthesis. Relevant enzymes: acetoacetyl-CoA thiolase, NAD- and NADP-dependent 3-hydroxybutyryl-CoA dehydrogenase, 3-hydroxybutyryl-CoA dehydratase, and NAD-dependent butyryl-CoA dehydrogenase.

Butyrate is produced by several fermentation processes performed by obligate anaerobic bacteria. This fermentation pathway was discovered by Louis Pasteur in 1861. Examples of butyrate-producing species of bacteria:

• Clostridium butyricum
• Clostridium kluyveri
• Clostridium pasteurianum
• Faecalibacterium prausnitzii
• Fusobacterium nucleatum
• Butyrivibrio fibrisolvens
• Eubacterium limosum

The pathway starts with the glycolytic cleavage of glucose to two molecules of pyruvate, as happens in most organisms. Pyruvate is oxidized into acetyl coenzyme A catalyzed by pyruvate:ferredoxin oxidoreductase. Two molecules of carbon dioxide (CO₂) and two molecules of hydrogen (H₂) are formed as waste products. Subsequently, ATP is produced in the last step of the fermentation. Three molecules of ATP are produced for each glucose molecule, a relatively high yield. The balanced equation for this fermentation is

C₆H₁₂O₆ → C₄H₈O₂ + 2CO₂ + 2H₂

Other pathways to butyrate include succinate reduction and crotonate disproportionation.

Action	Responsible enzyme
Acetyl coenzyme A converts into acetoacetyl coenzyme A	acetyl-CoA-acetyl transferase
Acetoacetyl coenzyme A converts into β-hydroxybutyryl CoA	β-hydroxybutyryl-CoA dehydrogenase
β-hydroxybutyryl CoA converts into crotonyl CoA	crotonase
Crotonyl CoA converts into butyryl CoA (CH3CH2CH2C=O−CoA)	butyryl CoA dehydrogenase
A phosphate group replaces CoA to form butyryl phosphate	phosphobutyrylase
The phosphate group joins ADP to form ATP and butyrate	butyrate kinase

Several species form acetone and n-butanol in an alternative pathway, which starts as butyrate fermentation. Some of these species are:

• Clostridium acetobutylicum, the most prominent acetone and butanol producer, used also in industry
• Clostridium beijerinckii
• Clostridium tetanomorphum
• Clostridium aurantibutyricum

These bacteria begin with butyrate fermentation, as described above, but, when the pH drops below 5, they switch into butanol and acetone production to prevent further lowering of the pH. Two molecules of butanol are formed for each molecule of acetone.

The change in the pathway occurs after acetoacetyl CoA formation. This intermediate then takes two possible pathways:

• acetoacetyl CoA → acetoacetate → acetone
• acetoacetyl CoA → butyryl CoA → butyraldehyde → butanol

For commercial purposes Clostridium species are used preferably for butyric acid or butanol production. The most common species used for probiotics is Clostridium butyricum.

Butyrate can be produced by dietary fibers through two different metabolic pathways. The first metabolic pathway is, butyryl-CoA is phosphorylated to form butyryl-phosphorylated to form butyryl-phosphate and transformed to butyrate via butyrate kinase. The second pathway, the CoA part of butyryl-CoA is transferred to acetate via butyryl-CoA: acetate CoA-transferase, leading to the formation of butyrate and acetyl-CoA. These metabolic pathways are how the butyrate is produced.

Inflammation of The Gut

When butyrate is present in the intestine, IFN-γ, TNF-α, IL-6, and IL-8 are inhibited. These are proinflammatory cytokines which increase inflammation and can cause tissue destruction. Butyrate is also capable of inducing IL-10 and TGF-β which are anti-inflammatory cytokines. Short-chain fatty acids are capable of modifying neutrophil recruitment, which improves immune response. This shows clinical significance in inflammatory bowel disease due to its chronic inflammatory nature. In inflammatory bowel disease it is seen that there is a reduction of butyrate-producing bacteria which greatly diminishes the defense mechanisms of the mucosal barrier of the gut.