Formate cross‐feeding and cooperative metabolic interactions revealed by transcriptomics in co‐cultures of acetogenic and amylolytic human colonic bacteria

Abstract

Summary Interspecies cross‐feeding is a fundamental factor in anaerobic microbial communities. In the human colon, formate is produced by many bacterial species but is normally detected only at low concentrations. Ruminococcus bromii produces formate, ethanol and acetate in approximately equal molar proportions in pure culture on RUM‐RS medium with 0.2% Novelose resistant starch (RS3) as energy source. Batch co‐culturing on starch with the acetogen Blautia hydrogenotrophica however led to the disappearance of formate and increased levels of acetate, which is proposed to occur through the routing of formate via the Wood Ljungdahl pathway of B. hydrogenotrophica . We investigated these inter‐species interactions further using RNAseq to examine gene expression in continuous co‐cultures of R. bromii and B. hydrogenotrophica . Transcriptome analysis revealed upregulation of B. hydrogenotrophica genes involved in the Wood‐Ljungdahl pathway and of a 10 gene cluster responsible for increased branched chain amino acid fermentation in the co‐cultures. Cross‐feeding between formate‐producing species and acetogens may be a significant factor in short chain fatty acid formation in the colon contributing to high rates of acetate production. Transcriptome analysis also indicated competition for the vitamin thiamine and downregulation of dissimilatory sulfate reduction and key redox proteins in R. bromii in the co‐cultures, thus demonstrating the wide‐ranging consequences of inter‐species interactions in this model system.

High-Throughput Sequencing and Unsupervised Analysis of Formyltetrahydrofolate Synthetase (FTHFS) Gene Amplicons to Estimate Acetogenic Community Structure

“…Therefore, acetogens are important microorganisms for the circular bio-economy and for mitigating climate change ( Oren, 2012 ; Liew et al, 2016 ; Müller, 2019 ; Wiechmann and Müller, 2019 ). Acetogens are also abundantly present in the human gut, but their role in human gut physiology and the gut-brain relationship require further investigation (e.g., Gibson et al, 1990 ; Leclerc et al, 1997 ; Ohashi et al, 2007 ; Rey et al, 2010 ; Laverde Gomez et al, 2019 ). Moreover, some acetogens have been found to associate with plants in aquatic habitats and can fix atmospheric nitrogen ( Küsel et al, 1999 ; Pester and Brune, 2006 ; Ohkuma et al, 2015 ).…”

Blautia—a new functional genus with potential probiotic properties?

“…A study found that by using 0.2% resistant starch as an energy source, R. bromii produces formic acid, ethanol, and acetic acid in approximately equal molar ratios on RUM-RS medium. 9 However, batch co-culture with acetogenic bacteria B. hydrogenotrophica on starch resulted in the disappearance of formic acid with an increase in acetic acid levels. RNA sequencing was used to further study the interspecific interactions to detect gene expression in continuous co-cultures of R. bromii and B. hydrogenotrophica.…”

“…Crossfeeding between formic acid-producing species and acetic acid-producing species may play an important role in the formation of SCFAs in the colon and contribute to the massive production of acetic acid. 9 As a key hydrogen-consuming anaerobic microorganism, B. hydrogenotrophica has been reported to mediate regulation related to the coexistence of anaerobic respiratory pathways. B. hydrogenotrophica consumes H 2 and CO 2 via the Wood-Ljungdahl pathway to produce acetic acid -a pathway significantly activated when coexisting with Bifidobacterium bifidum.…”

“…[5][6][7] This genus has also been revealed to play a certain role in biotransformation and crosstalk with other intestinal microorganisms. 8,9 Although Blautia has shown a series of potential probiotic properties, there is no comprehensive understanding of this genus, probably due to the lack of a comprehensive review. The Ninth Edition of Bergey's Manual of Systematic Bacteriology contains no description of the genus Blautia, only some introduction to the previous species belonging to the genus Clostridium or Ruminococcus and a summary of the characteristics of the type strains.…”

Synthetic gut microbiome: Advances and challenges

“…This could increase our understanding of gut ecology and promote the design of a synthetic microbial community representative of balanced human gut microbiota by mapping the keystone species into a stable microbiota and comparing it with diseased microbiota. Experiments involving co-cultures of core gut microbes have shown fascinating cross-feeding pathways, which involve the use of short chain fatty acids (SCFAs) [29] and have identified properties associated with major metabolic pathways for amino acid and vitamin metabolism, in combination with molecular analysis techniques [30] , [31] . There are several routes for obtaining reliable core gut microbiota.…”