Putting the microbiota to work: Epigenetic effects of early life antibiotic treatment are associated with immune-related pathways and reduced epithelial necrosis following Salmonella Typhimurium challenge in vitro

Abstract

Salmonella enterica serovar Typhimurium is an animal welfare and public health concern due to its ability to parasite livestock and potentially contaminate pork products. To reduce Salmonella shedding and the risk of pork contamination, antibiotic therapy is used and can contribute to antimicrobial resistance. Here we hypothesized that immune system education by the microbiota can play a role in intestinal resilience to infection. We used amoxicillin (15mg/Kg) to modulate the intestinal microbiome of 10 piglets, paired with same age pigs that received a placebo (n = 10) from 0 to 14 days of age. Animals were euthanized at 4weeks old. Each pig donated colon sections for ex vivo culture (n = 20 explants/pig). Explants were inoculated with S. Typhimurium, PBS or LPS (n = 6 explants/pig/group, plus technical controls). The gut bacteriome was characterized by sequencing of the 16S rRNA at 7, 21 days of age, and upon in vitro culture. Explants response to infection was profiled through high-throughput mRNA sequencing. In vivo antibiotic treatment led to β-diversity differences between groups at all times (P<0.05), while α-diversity did not differ between amoxicillin and placebo groups on day 21 and at euthanasia (P<0.03 on day 7). Explant microbiomes were not different from in vivo. In vitro challenge with S. Typhimurium led to lower necrosis scores in explants from amoxicillin-treated pigs, when compared to explants placebo-treated pigs (P<0.05). This was coupled with the activation of immune-related pathways in explants from amoxicillin-treated pigs (IL-2 production, NO production, BCR activation), when compared to placebo-treated pigs. In addition, several DNA repair and intestinal wound healing pathways were also only activated in explants from amoxicillin-treated pigs. Taken together, these findings suggest that immune education by the amoxicillin-disturbed microbiota may have contributed to mitigate intestinal lesions following pathogen exposure.

In Vitro Screening of Non-Antibiotic Components to Mitigate Intestinal Lesions Caused by Brachyspira hyodysenteriae, Lawsonia intracellularis and Salmonella enterica Serovar Typhimurium

“…Surprisingly, a lower degree of epithelial coverage was observed in explants exposed to compound F alone than explants exposed to B. hyodysenteriae ( Figure 1 A,B). It is known that colon explants harbor a microbiota compositionally similar to the donor pig prior to euthanasia [ 72 ]. Thus, we postulate that compound F may have served as a substrate for the microbiota already present in the explants, leading to bacterial overgrowth.…”

Raw potato starch diet supplement in weaned pigs could reduce Salmonella Typhimurium infection by altering microbiome composition and improving immune status

“…Pigs are an important non-typhoidal Salmonella infection source for humans, especially Salmonella enterica serovar Typhimurium (ST) ( 2 ). Intestinal inflammation caused by Salmonella infection can disrupt commensal microbiota and gut barriers, resulting in the bacteria colonizing the tissues of the host intestine ( 3 , 4 ), leading to diarrhea, fibrinonecrotic enterocolitis, and dehydration in pigs ( 5 ).…”

Effects of dietary supplementation of Pediococcus pentosaceus strains from kimchi in weaned piglet challenged with Escherichia coli and Salmonella enterica

“…Salmonella enterica (SE) has a wide host range, including pigs and humans, causes intestinal diseases. In pigs, SE causes fibrino necrotic enterocolitis, diarrhea, and dehydration [5].…”