The butyrate-producing and spore-forming bacterial genus Coprococcus as a potential biomarker for neurological disorders

Abstract

The host-intestinal microbiome interaction has gained much scientific attention in the past two decades, boosted by advances in DNA sequencing and cultivation techniques. An accumulating amount of evidence shows that gut microbes play crucial roles in gut homeostasis, immune system education, and are associated with quality-of-life indicators. Beneficial health factors are associated with the digestion of dietary fibres in the colon and the subsequent production of short-chain fatty acids, including acetate, propionate, and butyrate. Coprococcus is a butyrate-producing genus in the phylum Firmicutes, and its abundance is inversely correlated with several neuropsychological and neurodegenerative disorders. Case-control studies provide strong evidence of decreased abundance of Coprococcus spp. in depressed individuals. The species Coprococcus eutactus has the unique capacity to use two separate pathways for butyrate synthesis and has been found to be depleted in children with delayed language development and adults with Parkinson's disease. The combined literature on Coprococcus and the gut microbiota-brain axis points towards enhanced butyrate production and reduced colonisation of pathogenic clades as factors explaining its association with health effects. The genus Coprococcus is a promising candidate for a mental health biomarker and an interesting lead for novel dietary-based preventive therapies for specific neurological disorders.

Keywords: Coprococcus eutactus; depression; fibre fermentation; gut–brain axis; short-chain fatty acids.

Coprococcus as a potential biomarker and modulator of neurological disorders. 1. Ingestion of C. eutactus spores during early infancy. 2. Germination of spores in the gut. 3. A fibre-rich diet strengthens colonisation of C. eutactus. 4. C. eutactus produces short-chain fatty acids (SCFAs) during fibre fermentation. It has multiple butyrate production pathways. 5. Colonocytes take up SCFAs via facilitated diffusion or via free fatty acid receptors (FFARs). Butyrate metabolism by colonocytes improves the epithelial barrier function. 6. The uptake of SCFAs leads to the secretion of glucagon-like peptide 1 (GLP-1) and anorexigenic peptide YY (PYY). These peptides suppress appetite and may have neurological effects. 7. The gut–brain axis constitutes SCFAs and peptides transported via the blood or SCFA signalling via the vagus nerve. The implied neurological effects are indicated in the top-right corner. *Specifically associated with C. eutactus. a.a., amino acids; BBB, blood–brain barrier; HPA, hypothalamic–pituitary–adrenal; OCD, obsessive–compulsive disorder. Created with BioRender.com.

Figure 1.

Phylogenetic tree and microscopic characteristics of Coprococcus. (A) Evolutionary relationships of Coprococcus species and their closest human gut bacteria relatives. Bootstrap values are shown at branches. Image retrieved from Alessi et al. (2020). (B) Gram-stained photomicrograph depicting a number of chains of Gram-positive, anaerobic, coccoid Coprococcus eutactus bacteria. Image retrieved from the Public Health Image Library (1976). (C) Transmission electron microscopy image of cultured C. eutactus cells. Arrows indicate spore ultrastructures. Image retrieved from Browne et al. (2016).

Figure 2.

Degradation pathways for carbohydrates into short-chain fatty acids (SCFAs). Overview of carbohydrate break-down into SCFAs. Image reproduced from Parada Venegas et al. (2019).

Figure 3.

The butyrate synthesis pathways. The four bacterial butyrate synthesis pathways were retrieved from a study by Vital et al. (2014). Major enzymes are indicated and terminal genes are highlighted in red. Bcd, butyryl-CoA dehydrogenase (including electron transfer protein α and β subunits); Ptb, phosphate butyryltransferase; 4Hbt, butyryl-CoA:4-hydroxy-butyrate CoA transferase; But, butyryl-CoA:acetate CoA transferase; Ato, butyryl-CoA:acetoacetate CoA transferase; Buk, butyrate kinase.