7.2 Microbial metabolism of dietary components

Gut microbes play a crucial role in breaking down food we can't digest. They ferment carbs, proteins, and lipids, producing short-chain fatty acids and other metabolites. These compounds impact our health, affecting everything from gut function to immune responses.

The microbiome's ability to digest fiber and produce vitamins contributes to our nutrition. Different fiber types promote growth of specific bacteria, influencing gut diversity. Microbial metabolism also affects our energy balance, appetite, and nutrient absorption, highlighting the microbiome's importance in nutrition.

Microbial Fermentation of Dietary Components

Carbohydrate Fermentation Pathways

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• Microbial fermentation of dietary carbohydrates occurs through glycolysis followed by various fermentation pathways
  • Lactic acid fermentation converts pyruvate to lactate
  • Mixed acid fermentation produces multiple acids (acetic, lactic, succinic)
  • Alcohol fermentation yields ethanol and CO2
• Pentose phosphate pathway metabolizes pentose sugars (ribose, xylose) derived from dietary components
• Short-chain fatty acids (SCFAs) production results from carbohydrate fermentation
  • Primary SCFAs include acetate, propionate, and butyrate
  • SCFAs serve as energy sources for colonocytes
  • SCFAs influence gut health, immune function, and metabolism

Protein and Lipid Fermentation

• Protein fermentation by gut microbes involves multiple processes
  • Deamination removes amino groups from amino acids
  • Decarboxylation removes carboxyl groups from amino acids
  • Stickland reaction pairs amino acid oxidation and reduction
• Lipid metabolism by gut microbes includes several steps
  • Hydrolysis of triglycerides into fatty acids and glycerol
  • β-oxidation breaks down fatty acids into acetyl-CoA
  • Fermentation of glycerol produces propionate or butyrate

Factors Influencing Microbial Fermentation

• Crossfeeding between microbial species enables complete breakdown of complex dietary components
  • Example: One species breaks down complex carbohydrates, another ferments the resulting simple sugars
• Fermentation pathways influenced by environmental factors in the gastrointestinal tract
  • pH affects enzyme activity and microbial growth (acidic in stomach, neutral in intestines)
  • Oxygen availability determines aerobic vs anaerobic metabolism (low oxygen in colon)
  • Substrate availability varies along the digestive tract (higher in proximal colon)

Microbial Metabolites and Health

Short-Chain Fatty Acids (SCFAs)

• SCFAs produced from carbohydrate fermentation offer various health benefits
  • Acetate serves as an energy source for peripheral tissues
  • Propionate regulates hepatic gluconeogenesis and satiety
  • Butyrate provides energy for colonocytes and has anti-inflammatory properties
• SCFAs influence gut health by maintaining intestinal barrier function
• SCFAs modulate immune function by regulating T cell differentiation and cytokine production

Protein Fermentation Metabolites

• Branched-chain fatty acids (BCFAs) result from protein fermentation
  • Isobutyrate and isovalerate are common BCFAs
  • BCFAs may have both positive (energy source) and negative (pro-inflammatory) effects on gut health
• Hydrogen sulfide production from sulfur-containing amino acids
  • Toxic to colonocytes at high concentrations (>0.5 mM)
  • Acts as a signaling molecule at lower levels (<50 μM)
• Indoles and phenolic compounds derived from aromatic amino acids
  • Indole-3-propionic acid acts as an antioxidant
  • p-Cresol may have negative effects on intestinal barrier function

Other Microbial Metabolites

• Trimethylamine (TMA) produced from choline and L-carnitine metabolism
  • Converted to trimethylamine N-oxide (TMAO) in the liver
  • High TMAO levels associated with increased cardiovascular disease risk
• Secondary bile acids produced by microbial metabolism of primary bile acids
  • Deoxycholic acid and lithocholic acid are common secondary bile acids
  • Influence lipid absorption, glucose homeostasis, and potentially cancer risk
• Vitamins synthesized by gut microbes contribute to host nutrition
  • Vitamin K (menaquinones) important for blood clotting
  • B vitamins (biotin, folate, cobalamin) support various metabolic processes

Gut Microbiome in Digestion of Fiber

Microbial Enzymes for Fiber Breakdown

• Gut microbiome possesses enzymes to break down complex polysaccharides indigestible by human enzymes
  • Cellulases degrade cellulose (plant cell walls)
  • Hemicellulases break down hemicellulose (xylan, arabinoxylan)
  • Pectinases digest pectin (fruit cell walls)
• Microbial fermentation of dietary fibers produces beneficial metabolites
  • Short-chain fatty acids (acetate, propionate, butyrate)
  • Gases (hydrogen, carbon dioxide, methane)

Fiber Types and Microbial Populations

• Different types of dietary fibers selectively promote growth of specific microbial populations
  • Soluble fibers (inulin, fructo-oligosaccharides) promote Bifidobacterium growth
  • Insoluble fibers (cellulose, lignin) increase Bacteroidetes abundance
  • Fermentable fibers (resistant starch) enhance butyrate-producing bacteria
• Fiber type influences overall gut microbiome composition
  • High-fiber diets associated with increased microbial diversity
  • Low-fiber diets may lead to loss of beneficial microbial species

Polyphenol Metabolism

• Gut microbes metabolize polyphenols through various pathways
  • Deglycosylation removes sugar moieties from polyphenols
  • Ring fission breaks down flavonoid structures
  • Dehydroxylation modifies hydroxyl groups on polyphenols
• Microbial metabolism of polyphenols produces bioactive metabolites
  • Equol from daidzein (soy isoflavone) has estrogenic effects
  • Urolithins from ellagitannins (pomegranate) have anti-inflammatory properties
• Lignans metabolized by gut microbes produce enterolactone and enterodiol
  • Associated with potential anticancer effects
  • May have weak estrogenic activity

Microbial Metabolism and Host Energy Balance

Energy Contribution and Nutrient Absorption

• Microbial production of short-chain fatty acids provides additional energy to the host
  • Contributes up to 10% of daily caloric intake
  • 1 g of fermented fiber yields approximately 2 kcal of energy
• Gut microbes modulate expression of host genes involved in energy metabolism
  • Influence fat storage through regulation of lipoprotein lipase
  • Affect energy expenditure by modulating brown adipose tissue activity
• Microbial metabolism impacts mineral absorption
  • SCFA production lowers gut pH, enhancing calcium and magnesium solubility
  • Phytase-producing bacteria break down phytates, improving iron absorption

Lipid Metabolism and Vitamin Production

• Gut microbiome influences lipid absorption and metabolism
  • Modifies bile acid profiles, affecting fat emulsification and absorption
  • Regulates genes involved in lipid transport (FIAF, CD36)
• Microbial production of vitamins contributes to host nutrition
  • Vitamin K2 (menaquinone) synthesis by Bacteroides and Eubacterium
  • B vitamin production (biotin, folate, cobalamin) by various gut bacteria
• Microbes can compete with the host for certain nutrients
  • Vitamin B12 uptake by Bacteroides thetaiotaomicron may reduce host availability

Appetite Regulation and Nutrient Sensing

• Microbial metabolism influences appetite and satiety
  • SCFAs stimulate production of satiety hormones (PYY, GLP-1)
  • Metabolites affect vagal nerve signaling to the brain
• Gut microbes impact nutrient sensing and glucose homeostasis
  • Butyrate enhances insulin sensitivity
  • Microbial metabolites influence intestinal gluconeogenesis