Table 1.
Summary of the main metabolic pathways and corresponding Lachnospiraceae taxa involved in the production of compounds affecting human health. The beneficial and harmful effects are referred to the main diseases showing Lachnospiraceae variations.
| Taxa | Pathways (EC) | Metabolites | Beneficial Effect * | Harmful Effect | ||
|---|---|---|---|---|---|---|
| Butyril-CoA:acetate CoA trasferase (2.8.3.8) | butyrate | MD LD IBD | Strengthen the intestinal barrier through up-regulation of tight junctions and mucin production by enterocytes [61]. | MD LD | ||
| Anti-inflammatory effects by induction of regulatory T cells, downregulation of pro-inflammatory cytokines and the Toll-like receptor (TLR) 4 receptors [62]. | ||||||
| Activation of G protein-coupled receptor (GPR) 43 involved in the modulation of inflammation and stimulation of glucagon-like peptides (GLP) 1 and gastric inhibitory polypeptide; modulate appetite, reinforce insulin sensitivity and glucose metabolism [63,64]. | ||||||
| Eubacterium rectale | ||||||
| Roseburia spp., | ||||||
| E. halii L2-7, | ||||||
| Anaerostipes hadrus SSC/2, Coprococcus catus GD/7, | Activation of fatty acid oxidation and de novo synthesis and lipolysis inhibition, which in turn, decrease circulating lipid plasma levels and body weight [65]. | |||||
| Blautia spp. | ||||||
| GPR 43 binding suppresses colon inflammation therefore protect liver and down- regulate insulin signal transduction in adipose tissue [66]. | Elevated energy extraction in form of SCFAs related to a high intake of dietary carbohydrates [67]. | |||||
| MD LD | Lower expression of peroxisome proliferator-activated receptor-γ, and stimulation of uncoupling protein 2 and stimulate oxidative metabolism in liver and adipose tissue [70]. | Intestinotrophic effects of SCFAs mediated by GLP-2 which contributes to the development or maintenance of obesity through elevated intestinal absorption of energy (kcal) intake [68]. | ||||
| MD | Inhibition of Histone Deacetylases by altering the acetylation pattern of H3 and H4 histones and inducing beta-cell proliferation by inhibiting the p38/ERK apoptotic pathway [71,72]. | Dyslipidemia due to elevation of cholesterol and triglycerides that increasing the levels of Acetyl-CoA in obese patient and metabolic disturbance [69]. | ||||
| C. comes ATCC 27758, | Butyrate kinase | MDDMSS | ||||
| C. eutactus L2-50 | (2.7.2.7) | IBD | Significantly reduced circulating LPS levels [73]. Activation of GPR109A and inhibition of AKT and nuclear factor-κB p65 signaling pathways in IBD in mice [74]. | |||
| CKD | ||||||
| MSS | Increase anti-inflammatory CD4+ regulatory T cells and decrease pro-inflammatory Th1 and Th17 cells of in central nervous system. [75]. Upregulate tight junction and proteins claudin-5 and restore the blood-brain barrier permeability [76]. | |||||
| Ruminococcus inulinivorans A2-194, | Propanediol pathways (4.2.1.28, 1.2.1.87, 2.8.3.1.) | propionate | MD LD CKD | SCFA-stimulated GPR41 induce leptin production by adipocytes and lipid profile regulation [63,64]. Reduction of visceral fat and liver fat [77]. | MD | Substantial amounts of propionate entering into the mitochondrial tricarboxylic acid (TCA) cycle bypass the first four TCA enzymes, causing a shift in the cycle with a potential toxic effect [78,79]. |
| R. gnavus ATCC 29149, | ||||||
| R. torques L2-14, Blautia obeum A2.162, | ||||||
| E. hallii | ||||||
| C. catus, | Acrylate pathway (4.2.1.4, 1.3.8.7, 2.8.3.1.) | |||||
| Clostridium sp. MSTE9 (cluster XIVb) | ||||||
| R. gnavus ATCC 29149, | Mucin degradation (glycoside hydrolases (GH)) | IBD | Disproportionate increase of mucolytic bacteria could explain increased total mucosa-associated bacteria in IBD [80]. | |||
| R. gnavus ATCC 35913, | ||||||
| R. torques, | ||||||
| Dorea formicigenerans, | ||||||
| D. longicatena | ||||||
| Roseburia intestinalis L1-82, | acetate | MD LD CKD IBD | Inhibition of entero-pathogens; reduction of luminal pH, and increases the absorption of dietary nutrient [81,82]. Trophic effect on the colonic epithelium by raising the mucosal blood flux [83]. | MD | Increased production leads to activation of the parasympathetic nervous system and stimulation of insulin secretion. The role of acetate in driving obesity depends on the gut microbiota and on dietary fiber intake [84]. Transported to the portal circulation across the colonic mucosa, acetate passes through the liver and is regained in peripheral blood, where it is adsorbed by tissues involved in the rise of cholesterol synthesis [85]. | |
| R. intestinalis L1-952, | ||||||
| R. intestinalis L1-8152, | Acetate kinase | |||||
| Coprococcus catus, | (2.7.2.1) | LD | De novo lipogenesis and cholesterol genesis in the liver [86]. | |||
| Blautia sp. YL58, | Marked reduction in lipid accumulation in the adipose tissue, protects against accumulation of fat in the liver, improving the glucose tolerance [87]. | |||||
| B. obeum, | ||||||
| B. hansenii | ||||||
| Blautia hydrogenotrophica YIT 10080T, | p-cresol | CKD | The derived serum p-Cresyl sulphate a protein-derived uremic toxin is linked to cardiovascular and kidney damage [20]. | |||
| Tyrosine | ||||||
| B. obeum. | (2.6.1.1, 2.6.1.9, 4.1.1.83) | |||||
| Clostridium saccharolyticum WM1 | Tyrosine (4.1.99.2) | phenol | ||||
| Oribacterium sinus, | Tryptophan (4.1.99.1) | indole | MD LD CKD IBD | Activation of aryl-hydrocarbon receptor by microbially derived indoles, these molecules promotes tissue repair and homeostasis involving interleukin (IL)-22 [88]. | CKD | Indole and indoxyl sulfate affect arterial blood pressure via peripheral and central mechanisms dependent on serotonin signaling and contribute do cardiovascular disease in renal insufficiency [89]. |
| Lachnospiraceae | ||||||
| Coprococcus | Tryptophan | indole-propionic acid | MD | Engage the pregnane X receptor, leading to the upregulation of genes that regulate intestinal permeability and to the downregulation of TNF-α expression by enterocytes [90]. | ||
| MSS | Potent radical scavenging activity and neuroprotective properties [91]. | |||||
* The beneficial/harmful effects are referred to the relative diseases showed on the left side; Abbreviations: MD, metabolic diseases; LD, liver disease; IBD, inflammatory bowel disease; MDD, major depressive disorder; MSS, multiple sclerosis syndrome; CKD, chronic kidney disease; LPS, lipopolysaccharide; NF-κB, nuclear factor-κB; TNF-α, tumor necrosis factor.