Murine fecal microbiota transplantation lowers gastrointestinal pathogen loads and dampens pro-inflammatory immune responses in Campylobacter jejuni infected secondary abiotic mice

Abstract

Conventional mice are protected from Campylobacter jejuni infection by the murine host-specific gut microbiota composition. We here addressed whether peroral fecal microbiota transplantation (FMT) might be an antibiotics-independent option to lower even high gastrointestinal C. jejuni loads in the infected vertebrate host. To address this, secondary abiotic mice were generated by broad-spectrum antibiotic treatment and perorally infected with C. jejuni by gavage. One week later, mice were stably colonized with more than 109 C. jejuni and subjected to peroral FMT from murine donors on three consecutive days. Two weeks post-intervention, gastrointestinal C. jejuni loads were up to 7.5 orders of magnitude lower following murine FMT versus mock challenge. Remarkably, FMT reversed C. jejuni induced colonic epithelial apoptosis, but enhanced proliferative and regenerative responses in the colon thereby counteracting pathogenic cell damage. Furthermore, FMT dampened both, innate and adaptive immune cell responses in the large intestines upon C. jejuni infection that were accompanied by less C. jejuni-induced colonic nitric oxide secretion. Our study provides strong evidence that novel probiotic formulations developed as alternative option to FMT in severe intestinal inflammatory morbidities including Clostridoides difficile infection might be effective to treat campylobacteriosis and lower pathogen loads in colonized vertebrates including farm animals.

Heligmosomoides bakeriandToxoplasma gondiico-infection leads to increased mortality associated with intestinal pathology

“…We also found that the number of T cells (CD8 + , CD4 + , γδ and NKT) were increased at d10 post-infection in the liver (data not shown). Our results agree with previous studies showing increases in T cells in the liver d10 post-Tg infection [87], as well as a general increase in liver pathology, infiltrates and inflammation [88].…”

The conundrum of colonization resistance against Campylobacter reloaded: The gut microbota composition in conventional mice does not prevent from Campylobacter coli infection

“…Adult wildtype mice harboring a conventional gut microbiota, for instance, are protected from stable C. jejuni colonization even following peroral infection with high bacterial loads [17]. This physiological colonization resistance provided by the intact complex murine gut microbiota is abrogated upon broad-spectrum antibiotic treatment, however, rendering mice susceptible to intestinal C. jejuni colonization following peroral pathogenic challenge [18][19][20]. This also holds true for conditions that are accompanied by gut microbiota shifts towards elevated intestinal loads of commensal enterobacteria, including Escherichia coli [16,21].…”

The Host-Specific Intestinal Microbiota Composition Impacts Campylobacter coli Infection in a Clinical Mouse Model of Campylobacteriosis

“…In summary, our present study revealed that peroral C. coli infection results in pronounced clinical signs, apoptotic, and pro-inflammatory immune responses in the intestinal tract of IL-10 −/− mice harboring a human intestinal microbiota, whereas IL-10 −/− mice with a murine intestinal microbiota were stably colonized by the pathogen, but protected from disease manifestations. Given that murine FMT treatment could effectively dampen pathogen-induced apoptotic epithelial and pro-inflammatory immune responses in the large intestines of C. jejuni -infected microbiota-depleted, as well as of “humanized”, IL-10 −/− mice [ 27 , 31 ], these findings collectively provide strong evidence that microbiota modifications by pre- or probiotics, for instance, might open novel avenues for future treatment strategies in the combat of campylobacteriosis in humans.…”

“…Our cultural analyses and culture-independent molecular approaches additionally assessing fastidious and non-cultivable bacteria revealed, however, that the host-specific differences in numbers of the most common intestinal bacterial groups, genera, and species between respective fecal donor suspensions could also be observed in the intestinal tract of IL-10 −/− mice after establishment of the complex human versus murine intestinal microbiota following peroral FMT. Even though the methods applied here have their limitations regarding the possibilities to provide a complete picture of the commensal ecological conditions within the gut lumen, the combinatory approach of quantitative “culturomics” plus 16S rRNA-based analyses have been proven highly reliable for a comprehensive survey of differences in host-specific intestinal microbiota compositions [ 15 , 16 , 24 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ]. One needs to take into account, however, that during processing of the fecal donor samples, including freezing and thawing, individual bacterial strains might have been reduced and not fully established within the intestinal tract upon FMT [ 27 , 30 , 35 ].…”