Table 2.
Major amino acid-fermenting bacteria in the digestive tract.
| Amino acids | Intestinal bacteria | Metabolite | Related mechanisms in PD | Trends in PD | Niches | References |
|---|---|---|---|---|---|---|
| Phenylalanine | Subdoligranulum | Phenylpropionate | Phenylalanine is the precursor of dopamine and could participate in protein sequences in all tissues | Ascend | Rumen | Hirayama et al., 2016; Dodd et al., 2017 |
| Lactobacillus | Phenyl lactate | Small intestine | ||||
| Clostridium | Phenylacetate | Cecum | ||||
| Pepto streptococcus spp. | Phenyl pyruvic acid | Colon | ||||
| 4-OH-phenylpyruvic acid | ||||||
| Ammonia | ||||||
| CO2 | ||||||
| Asparagine | Fusobacterium nucleatum | Aspartic acid | Related to oxidative stress and dopamine cell degeneration in PD | Descend | Small intestine | Nagaraja et al., 2021 |
| Escherichia coli | Ammonia | Large intestine | ||||
| Klebsiella pneumoniae | CO2 | Colon | ||||
| Campylobacter jejuni | Feces | |||||
| Bacteroides fragilis | ||||||
| Tryptophan | Lactobacillus spp. | Indole | Associated with psychiatric problems in advanced PD | Descend | Stomach | Hatano et al., 2016; Dehhaghi et al., 2019; Liu B. et al., 2021; Liu J. R. et al., 2021 |
| Bifidobacterium spp. | Indole ethanol | Small intestine | ||||
| Clostridium spp. | Indolepropionic acid | Colon | ||||
| Pepto streptococcus spp. | Indolelactic acid | |||||
| Bacteroides spp. | Indoleacetic acid | Feces | ||||
| Clostridium sporogenes | Skatole | |||||
| Ruminococcus gnavus | Tryptamine | |||||
| Indolealdehyde | ||||||
| Indoleacrylic acid | ||||||
| Lysine | Clostridium sticklandii | Lysine-5,6-aminomutase | Acylation of lysine neutralizes may change the conformation of proteins | Ascend | Stomach | Potrykus et al., 2008; Wan et al., 2019 |
| Small intestine | ||||||
| Porphyromonas gingivalis | Lysine | Colon | ||||
| Feces | ||||||
| 2,3-aminomutase | ||||||
| 2,5-diaminohexanoate | ||||||
| Dehydrogenase | ||||||
| 3,5-diaminohexanoate | ||||||
| Dehydrogenase | ||||||
| 3,6-diaminohexanoic acid | ||||||
| Serine | Fusobacterium | Acetate | Signaling molecule to regulate the growth, repair, and maintenance of brain functions | Ascend | Stomach | Campbell et al., 1967; Schierack et al., 2007; Donatti et al., 2020 |
| Varium | Lactate | Small intestine | ||||
| Campylobacter jejuni | Pyruvate | Colon | ||||
| Bacteroides fragilis | Ammonia | |||||
| Acidaminococcus fermentans | Malate | Feces | ||||
| CO2 | Rumen | |||||
| Clostridium aminophilum | Cecum | |||||
| Clostridium perfringens | Stomach | |||||
| Clostridium sticklandii | Large intestine | |||||
| Pepto streptococcus spp. | ||||||
| Aspartic acid | Fusobacterium nucleatum | Asparagine | Related to oxidative stress, and dopamine cell degeneration in PD | Descend | Small intestine | Sugihara et al., 1974; Guccione et al., 2008 |
| Escherichia coli | Fumarate | Colon | ||||
| Oxaloacetate | ||||||
| Campylobacter jejuni | Feces | |||||
| Acidaminococcus | ||||||
| Fermentans | ||||||
| Bacteroides fragilis | ||||||
| Glutamine | Clostridium aminophilum | Pyroglutamate | Involved in the glutamate-glutamine cycle | Ascend | Mouth | Donatti et al., 2020; Kumari et al., 2020 |
| Selenomonas ruminantium | Acetate | Small intestine | ||||
| Acidaminococcus fermentans | Butyrate | Large intestine | ||||
| Ammonia | Stomach | |||||
| Clostridium perfringens | CO2 | |||||
| Colon | ||||||
| Pepto streptococcus spp. | Feces | |||||
| Streptococcus bovis | Rumen | |||||
| Campylobacter jejuni | Cecum | |||||
| Klebsiella pneumoniae | ||||||
| Escherichia coli | ||||||
| Fusobacterium nucleatum | ||||||
| Glutamate | Clostridium aminophilum | 2-Oxaloacetate | Participating in the disruption of the normal basal ganglia function, thus leading to neuronal death | Descend | Mouth | Donatti et al., 2020; Jiménez-Jiménez et al., 2020; Kumari et al., 2020 |
| Selenomonas ruminantium | Ammonia | Small intestine | ||||
| Acidaminococcus fermentans | GABA | Large intestine | ||||
| CO2 | ||||||
| Clostridium perfringens | Stomach | |||||
| Campylobacter jejuni | Colon | |||||
| Feces | ||||||
| Klebsiella pneumoniae | Cecum | |||||
| Escherichia coli | ||||||
| Fusobacterium varium | ||||||
| Fusobacterium nucleatum | ||||||
| Glutamic acid | Fusobacterium nucleatum | Glutamate | Glutamic acid is a precursor of glutathione and may reflect an increase in oxidative stress in the disease progression | Descend | Small intestine | Rychlik and Russell, 2002; Whitehead and Cotta, 2004; Anderson et al., 2009; Vascellari et al., 2020 |
| Fusobacterium varium | Ammonia | Large intestine | ||||
| Acetate | ||||||
| Escherichia coli | Butyrate | Stomach | ||||
| Selenomonas ruminantium | GABA | |||||
| Acidaminococcus fermentans | CO2 | |||||
| 2-Oxaloacetate | ||||||
| Clostridium aminophilum | 2-ketoglutarate | |||||
| Histidine | Fusobacterium nucleatum | Urocanate | Suppressive neurotransmitter effects and hormone secretion | Ascend | Mouth | Attwood et al., 1998; Kumari et al., 2020; Sylte et al., 2020 |
| Small intestine | ||||||
| Fusobacterium varium | Ammonia | Large intestine | ||||
| Klebsiella pneumoniae | Glutamic acid | |||||
| Histamine | Colon | |||||
| CO2 | Feces | |||||
| Rumen | ||||||
| Glycine | Fusobacterium nucleatum | Acetate | Glycine could stimulate the release of dopamine and acetylcholine | Ascend | Mouth | Luan et al., 2015; Kumari et al., 2020; Sánchez-Andrea et al., 2020 |
| Clostridium perfringens | Pyruvate | Small intestine | ||||
| Bacteroides fragilis | Serine | Large intestine | ||||
| Stomach | ||||||
| Escherichia coli | Colon | |||||
| Feces | ||||||
| Threonine | Fusobacterium nucleatum | Acetate | Signaling molecule to regulate the growth, repair, and maintenance of brain functions | Ascend | Mouth | Donatti et al., 2020; Wu and Deng, 2020; Karkache et al., 2021 |
| Escherichia coli | Ammonia | Small intestine | ||||
| Pepto streptococcus spp. | Propionate | Large intestine | ||||
| Clostridium sporogenes | n-butyrate | |||||
| Clostridium sticklandii | Ketobutyrate | Stomach | ||||
| Clostridium difficile | Lactate | Colon | ||||
| Clostridium perfringens | CO2 | Feces | ||||
| Megasphaera elsdenii | ||||||
| Acidaminococcus fermentans | ||||||
| Bacteroides fragilis | ||||||
| Arginine | Fusobacterium nucleatum | 2-Oxoarginine | Serve as a helpful clinical diagnostic biomarker for PD | Ascend | Mouth | Amano et al., 2020; Donatti et al., 2020; Martí I Líndez and Reith, 2021 |
| Escherichia coli | Guanidinoacetic acid | Small intestine | ||||
| Klebsiella pneumoniae | Creatine | Large intestine | ||||
| Clostridium sticklandii | Urea | Stomach | ||||
| Clostridium perfringens | Putrescine | Colon | ||||
| Selenomonas ruminantium | Spermine | Feces | ||||
| Agmatine | Cecum | |||||
| Ammonia | Rumen | |||||
| CO2 | ||||||
| Alanine | Staphylococcus aureus | Isovalerate | Alanine may point to mitochondrial dysfunction, oxidative stress, and inflammation markers in PD | Ascend | Small intestine | Nielsen et al., 2020 |
| Streptococcus spp. | Isocaproate | Large intestine | ||||
| Ammonia | Feces | |||||
| Gram negative bacteria | ||||||
| Escherichia coli | ||||||
| Selenomonas ruminantium | ||||||
| Prevotella spp. | ||||||
| Bacteroides spp. | ||||||
| Clostridium spp. | ||||||
| Ruminal bacteria | ||||||
| Valine | Staphylococcus aureus | Ammonia | Related to myelination dysfunction of the neurons. | Descend | Large intestine | Toczylowska et al., 2020 |
| Streptococcus spp. | CO2 | |||||
| Acetate | ||||||
| Escherichia coli | Isobutyrate | |||||
| Klebsiella spp. | ||||||
| Selenomonas ruminantium | ||||||
| Megasphaera elsdenii | ||||||
| Methionine | Klebsiella pneumoniae | S-adenosyl-L-methionine | Associated with hyperhomocysteinemia | Ascend | Small intestine | Toczylowska et al., 2020 |
| n-(3-oxododecanoyl) homoserine lactone | Colon | |||||
| Feces | ||||||
| Leucine | Pepto streptococcus spp. | Isovalerate | Contribute to muscle wasting, twitching, and tremors. | Descend | Rumen | Luan et al., 2015; Ma et al., 2020; Vascellari et al., 2020 |
| Isocaproate | Small intestine | |||||
| Clostridium bifermentans | Ammonia | Cecum | ||||
| CO2 | ||||||
| Clostridium sporogenes | Acetate | Colon | ||||
| Isobutyrate | Large intestine | |||||
| Clostridium sticklandii | ||||||
| Clostridium difficile | ||||||
| Prosthecobacter | ||||||
| Isoleucine | Pepto streptococcus spp. | Isovalerate | Contribute to muscle wasting, twitching, and tremors | Descend | Rumen | Kumari et al., 2020; Vascellari et al., 2020 |
| Clostridium bifermentans | Isocaproate | Small intestine | ||||
| Clostridium sporogenes | Ammonia | Cecum | ||||
| Clostridium sticklandii | CO2 | |||||
| Acetate | Colon | |||||
| Clostridium difficile | Isobutyrate | Large intestine | ||||
| Linoleic acid | Bacteroidaceae | 9-,13-oxoODEs | Associated with protective effects and may reflect an excess of oxidative stress | Descend | Small intestine | Vascellari et al., 2020 |
| Streptomyces griseorubens | Ammonia | Colon | ||||
| CO2 | ||||||
| Acetate | Feces | |||||
| Tyrosine | Clostridium | Ferulic acid | Tyrosine is then further hydroxylated to produce Dopa by tyrosine hydroxylase | Ascend | Stomach | Kumari et al., 2020 |
| Bacteroides | 4-Hydroxycinnamic acid | Small intestine | ||||
| Bifidobacterium | 4-Hydroxyphenylacetic acid | Colon | ||||
| 4-Hydroxyphenylpropionic acid | Feces | |||||
| Faecalibacterium | 3-Hydroxybenzoic acid | |||||
| Pyruvate | Faecalibacterium | Acetate | Reduced pyruvate may be related to impairment in energetic and repair functions | Descend | Rumen | Toczylowska et al., 2020; Shen et al., 2021 |
| Clostridium bifermentans | Formate | Small intestine | ||||
| Clostridium sporogenes | Lactate | Large intestine | ||||
| Lactoyl-CoA | ||||||
| Acryloyl-CoA | Cecum | |||||
| Propionyl-CoA | Colon | |||||
| Propionate |