Bacterial Information	Value
Taxonomy level	Species
NCBI Taxonomy ID	292800
Phylum	Firmicutes
Family	Oscillospiraceae
Genus	Flavonifractor
Gram stain	Gram-positive
Oxygen requirements	Strictly anaerobic
Spore-forming	Variable
Motile	Yes
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• Flavonifractor plautii
  • Table of Contents
  • Overview
  • Biological information
    • Detection
    • DSS-induced acute colitis
    • OVA-sensitised allergy model
    • Glycerol metabolism to DNA-reactive acrolein (reuterin system)
      • 3-Hydroxypropanal (reuterin)
      • Acrolein

Flavonifractor plautii are Gram-positive (Gram-variable after staining), motile bacteria. Spore production is variable, but the spore-producing gene spo0A is present. They appear as straight or slightly curved rods, ranging from 2 – 10 μm in length, either singly or in pairs. Cells can appear fusiform (wide in the middle, tapering off at both ends).

They are asaccharolytic, and only weakly ferment glucose, fructose, and ribose. They can metabolise quercetin and other flavanoids. Major ends products in TGY broth are acetic and butyric acids. Nitrate is not reduced, while production of indole and hydrogen sulfide (H₂S) is variable. Gelatin and meat are not digested. Lecithinase is not produced.

Colonies are minute, circular, convex, grey or white, and non-haemolytic. Major cellular fatty acids are C_14:0 and C_16:0. Genomic G+C content of DNA is 58-61.6 mol%.

F. plautii is involved in metabolism of dietary catechins, which belong to the flavanoid subclass of flavan-3-ols – these metabolites are associated with lower risk of cardiovascular diseases (Arts 2001)(Arts 2001) and chemoprotection (Arts 2002)(Theodoratou 2007)(Simons 2009), however it is not clear whether this results from catechins themselves or their metabolic products. Catechin metabolites are also associated with antioxidant, anti-inflammatory, anti-proliferative, and anti-platelet aggregative properties (Koga 2001)(Unno 2003)(Rechner 2005)(Schroeter 2006)(Larossa 2009).

Flavonifractor plautii is a commensal bacterium that is typically found in the gut microbiota of humans and animals. As a commensal, it has a mutually beneficial relationship with its host, and its presence is generally considered to be beneficial for host health.

F. plautii have been isolated from normal faecal flora, blood, intra-abdominal pus, and infected soft tissues (Carlier 2010).

Reduced symptoms of DSS colitis via suppression of IL-17 signalling.

Daily intragastric administration of 10⁸ colony-forming units (CFU) mildly attenuated DSS-induced acute colitis-related weight gain and disease activity index (DAI) (Mikami 2021). Diarrhoea and bloody stool scores were also improved, and colon length was longer compared to administration of PBS only at day 8, along with reversal of DSS-induced colon shortening in the F. plautii group at days 8.

T_H17 cells massively infiltrate the intestine in IBD patients, where they predominantly produce IL-17A; IL-17 signalling is triggered and amplified during the inflammatory process (Gálvez 2014). IL-23 is a cytokine that maintains and proliferates T_H17 cells in IBD (Weaver 2013). There was a trend towards decreased IL-17 and increased IL-10 at day 8 in F. plautii-treated mice, however a significant decrease in IL-17 at day 10 was not associated with a significant increase in IL-10.

Instead, by using harvested splenocytes from the C57BL/6 mice (stimulated in vitro with 50 ng/mL IL-6 and 2.5 ng/mL TGF-β1), the effect of bacterial lipoteichoic acids (LTA) on IL-17 signalling was investigated, following previous reports that bacterial LTA can reduce proliferation of effector CD4⁺ T cells. Treatment of the mouse splenocytes with any of F. plautii (FP), heat-killed F. plautii (HK-FP), F. plautii LTA (FP-LTA), or LTA from Staphylococcus aureus (SA-LTA) resulted in suppression of IL-17 production.

F. plautii administration suppresses Th2 inflammation and expands CD103+ DCs and Tregs in an OVA mouse model.

Ovalbumin (OVA)-sensitised BALB/c mice were treated by oral gavage with either 200 μL PBS or 10⁶ CFU F. plautii daily, 5 days per week, for 3 weeks, from 5 to 7 weeks of age. Mice were euthanised at 8 weeks, and splenocytes and the mesenteric lymph nodes (MLN) collected (Ogita 2020).

F. plautii administration reduced serum α-OVA IgE, IL-4, and IFN-γ compared to PBS-treated OVA-sensitised animals. It also reduced numbers of IL-4⁺CD4⁺ and IFN-γ⁺CD4⁺ T cells in the spleen, while increasing CD4⁺CD25⁺ T cells and CD103⁺CD11c⁺ dendritic cells (DCs). F. plautii administration also reduced GATA3 expression in the MLN.

Further, mice given F. plautii showed increased differentiation to CD103⁺ DC and Foxp3⁺ T cells among splenocytes and T and DC cells in the MLN. CD103⁺ are important for mucosal immune homeostasis (Ruane 2011).

This suggests that F. plautii inhibits T_H2 responses by instead activating T_reg and T_H1 cells – it has been previously reported that T_reg cells are induced and T_H2 responses are suppressed in cases where there are increased CD103⁺ DCs tolerant to the Gram-positive bacteria Bifidobacterium, Lactobacillus rhamnosus GG and F. plautii (Fu 2017)(Zhang 2018). In the case of L. rhamnosus GG, its administration was protective against OVA-induced airway inflammation through expansion of mesenteric CD103⁺ DCs and accumulation of airway and intestinal mucosal T_reg cells (Zhang 2018).

Production of 3-HPA is associated with health benefits and has broad-spectum bacteriocin activity.

Gut bacteria harbouring glycerol/diol dehydratases encoded by the pduCDE genes, including food microbes and gut commensals such as Limosilactobacillus reuteri, Anaerobutyricum hallii, F. plautii, and Blautia obeum metabolise glycerol and produce 3-hydroxypropanal (3-HPA; reuterin) during growth (Garcia 2022). 3-HPA exists in equilibrium with alongside its hydrate and dimer forms, and can be further metabolised to 1,3-propanediol (1,3-PD), comprising the multicomponent reuterin system (Engels 2016).

3-HPA has broad-spectrum antibiotic (bacteriocin) activity, and its production in the gut has been associated with beneficial effects, such as suppression of colorectal carcinogenesis (Bell 2022). Its antibiotic effects come from disruption of intracellular redox balance and protein modification, and it inhibits growth of Gram-positive and Gram-negative bacteria, yeasts, molds, and protozoa (Vollenweider 2003)(Vollenweider 2010).

Acrolein has cytotoxic effects and can damage intestinal epithelium and reduce barrier function.

Under physiological conditions, 3-HPA also dehydrates to acrolein. Acrolein also has antimicrobial activity as a result of its high reactivity as a chemical electrophile which allows it to covalently bind to cellular nucleophiles including DNA and proteins – this can give rise to toxic and mutagenic responses in exposed human cells (Marques 2021)(Moghe 2015)(Wang 2012)(Yang 2002).

Mice exposed to acrolein (5 mg/kg body weight – 3 times with 12 hour spacings) showed damage to the intestinal epithelial barrier, resulting in increased permeability and subsequent translocation of bacterial LPS into the circulation (Chen 2017). It also caused downregulation and/or redistribution of tight junction proteins (zonula occludens-1, occludin, and claudin-1) in addition to endoplasmic reticulum stress-mediated epithelial cell death (Chen 2017).