Oral Administration of Heat-Treated Lactobacilli Modifies the Murine Microbiome and Reduces Citrobacter Induced Colitis

Abstract

Significant evidence supports a relationship between the gut microbiome, inflammation, host response, and health, including the finding that a number of disorders are associated with disruption of the microbiome. In these disorders, a number of dietary interventions (including prebiotics, live probiotics, or heat-killed microbes) have been proposed to be curative or preventative agents. The use of heat-killed microbes has a number of benefits over living organisms, including reduced infection risk in vulnerable individuals, extended shelf life and the potential for use in combination with antimicrobial agents. We previously reported that murine chow supplemented with 5% ADR-159, a heat-treated fermentate generated by two Lactobacillus strains, altered both behavior and the microbiome of male mice. Now we show that ADR-159 fed female mice also display a similar microbiome shift as determined by 16S rDNA analysis. In particular, we observed a reduction of levels of Turicibacter and Clostridium sensu stricto. These subtle changes in the bacterial component of the microbiome were mirrored by changes in the virome. Extended consumption of the ADR-159 diet had no negative effect on general health and lipocalin 2 levels (LCN2; a proxy for inflammation), but we observed increased IL-17f and decreased IL-12α expression in the colon and decreased short chain fatty acid levels in the ADR-159 fed animals. Four weeks into the diet, half of the animals were dosed with Citrobacter to determine the effect of ADR-159 on infection and on pathogen induced colitis. Overall, our results suggest that while the ADR-159 diet does not prevent Citrobacter infection, it had an effect on Citrobacter-induced inflammation. In contrast to animals fed standard chow, ADR-159 fed animals did not show a reduction of small intestine length and increase of colon crypt depth, which occurred in control mice. These microbiological, histological, and immunological results provide evidence to support the impact of heat-treated microorganisms and their metabolites on the murine microbiome and health.

The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics

“…The study found that less abundant taxa were most affected. The same research group went on to use the same postbiotic in a mouse model of Citrobacter -induced colitis, which is characterized by a shortening of the small intestine and an increase in colon crypt depth 121 . The postbiotic did not prevent Citrobacter infection, but postbiotic-fed mice had a longer small intestine and reduced colon crypt depth compared with control animals that received standard mouse chow alone.…”

The role of the microbiome in gastrointestinal inflammation

“…Murine studies have shown the effect of postbiotics on gastrointestinal mucosa in a Citrobacter -induced colitis model [ 266 ], whereas the mechanistic impact on mucosal inflammation in humans is more limited to specific metabolites such as butyrate as in the case of diversion colitis [ 267 ]. However, clinical studies focussing on subjective outcomes such as symptom scores have shown benefit of postbiotics in IBS [ 268 ].…”

Probiotic Gastrointestinal Transit and Colonization After Oral Administration: A Long Journey

“…Furthermore, viable probiotics reaching the colon must also manage to colonize the intestinal mucosa in competition with the indigenous bacteria ( Zmora et al., 2018 ). Interestingly, several reports demonstrated that many of the effects obtained from viable cells of probiotics can also be realized from the dead probiotics ( Adams, 2010 ; Li et al., 2016 ; Warda et al., 2019 ; Warda et al., 2020 ). Since this review mainly concentrate on the adhesion-associated surface molecules, the detailed part of dead probiotics and their function will not be described here.…”