Emulsifiers are incorporated into many processed foods to extend shelf life and improve organoleptic properties. But accumulating evidence indicates that some non-absorbed synthetic emulsifiers, including carboxymethylcellulose (CMC) and polysorbate 80 (P80), can negatively impact intestinal microbiota, leading to microbiota encroachment, chronic low-grade intestinal inflammation and promotion of metabolic dysregulations, as well as depletion of the health-associated bacteria, Akkermansia muciniphila.
Previous research suggests A. muciniphila fortifies the mucosal barrier by stimulating mucus production and by inducing production of antimicrobial peptides such as Reg3γ.
A pilot clinical study of A. muciniphila suggested benefits in humans include a trend towards lowered fat-mass gain and decreased hip circumference, enhanced insulin sensitivity and reductions in endotoxaemia and inflammation in overweight subjects.
The goal of the current study therefore was to investigate the potential of A. muciniphila to prevent emulsifier disturbance of host-microbiota homeostasis in mice, as well as its impact on low-grade inflammation and metabolism.
The researchers found that daily administration of A. muciniphila protected mice from emulsifier-induced metabolic dysregulations and the low-grade intestinal inflammation thought to drive this state. Furthermore, A. muciniphila prevented emulsifier-induced shifts in microbiota composition and localisation, as well as protecting against colonic transcriptome alterations.
The researchers pose a potential mechanism of action is that A. muciniphila might act directly on microbiota, shifting its composition to one that is resistant to emulsifier’s perturbation.
"Such ability of A. muciniphila supports its use as a countermeasure to combat modern stressors that perturb host–microbiota interactions to promote metabolic syndrome and other chronic inflammatory diseases," the team asserts.
Mechanism of action
The current study, in line with previous reports, suggests that A. muciniphila can prevent emulsifier-induced microbiota encroachment and its impacts on inflammation and metabolism. Additionally, and surprisingly to the researchers in the current study, A. muciniphila also appeared to prevent emulsifier-induced changes of microbiota composition.
Hence, a possible explanation is that the primary mechanism of action for A. muciniphila is through the fortification of the mucus barrier, as suggested by its ability to reverse emulsifier-induced depletion in colonic goblet cells, and that, in vivo, altered microbiota composition is a consequence of encroachment-induced inflammation rather than the reflection of a direct emulsifier-microbiota interaction, as suggested by the team's in vitro studies.
However, conversely, the team did not observe alteration in mucus gene expression in response to A. muciniphila, by itself or in presence of emulsifiers. Therefore, they propose an alternate and/or additional potential mechanism of A. muciniphila action.
"We postulate that A. muciniphila might act directly on microbiota, shifting its composition to one that is resistant to emulsifier’s perturbation. Indeed, our data accords with this suggested mechanism, but further studies are needed to understand how A. muciniphila can possibly protect microbiota against emulsifiers.
"We envision use of ex vivo colonic explants to study the dynamic of mucus secretion and function, which, together with, longitudinal investigation of microbiota composition evolution during A. muciniphila supplementation, will elucidate impact of this probiotic on the mucus–microbiota relationship.
"Furthermore, it remains important to investigate the specificity of A. muciniphila-mediated protection by analysing the impacts of other commensal bacteria... Collectively, we anticipate these studies will yield mechanistic understanding of how A. muciniphila protects against dietary emulsifier consumption."
Mice were exposed to water (control group, N=10), CMC (N=10) or P80 (N=10) diluted in the drinking water for 9 weeks, with solutions changed every week. For each group, half of the mice were treated with 400 µL of sterile PBS and half of the mice (N=5) were treated with 400 µL of PBS containing 2.528×108 colony-forming units of A. muciniphila.
Body weights were measured every week. Food intake was measured twice during the same week. Fresh faeces were collected at days 0, 49 and 63 for downstream analysis. After 9 weeks of treatment, mice were euthanised, and one side of the epididymal fat pad weight, spleen weight, colon weight and colon length were measured.
Source: BMJ Gut Microbiota
"Akkermansia muciniphila counteracts the deleterious effects of dietary emulsifiers on microbiota and host metabolism"
Authors: Daniel, N., Gewirts. A. T., and Chassaing. B.