Colonic innate immune defenses and microbiota alterations in acute swine dysentery.

Brachyspira hyodysenteriae, an etiologic agent of swine dysentery (SD), is known for causing colitis. Although some aspects of colonic defenses during infection have been described previously, a more comprehensive picture of the host and microbiota interaction in clinically affected animals is required. This study aimed to characterize multiple aspects of colonic innate defenses and microbiome factors in B. hyodysenteriae-infected pigs that accompany clinical presentation of hemorrhagic diarrhea. We examined colonic mucus barrier modifications, leukocyte infiltration, cathelicidin expression, as well as microbiome composition. We showed that B. hyodysenteriae infection caused microscopic hemorrhagic colitis with abundant neutrophil infiltration in the colonic lamina propria and lumen, with minor macrophage infiltration. Mucus hypersecretion with abundant sialylated mucus in the colon, as well as mucosal colonization by [Acetivibrio] ethanolgignens, Lachnospiraceae, and Campylobacter were pathognomonic of B. hyodysenteriae infection. These findings demonstrate that B. hyodysenteriae produces clinical disease through multiple effects on host defenses, involving alterations of mucosal innate immunity and microbiota. Given that B. hyodysenteriae is increasingly resistant to antimicrobials, this understanding of SD pathogenesis may lead to future development of non-antibiotic and anti-inflammatory alternative therapeutics.

Fish oil mitigates myosteatosis and improves chemotherapy efficacy in a preclinical model of colon cancer.

BACKGROUND: This study aimed to assess whether feeding a diet containing fish oil was efficacious in reducing tumor- and subsequent chemotherapy-associated myosteatosis, and improving tumor response to treatment. METHODS: Female Fischer 344 rats were fed either a control diet for the entire study (control), or switched to a diet containing fish oil (2.0 g /100 g of diet) one week prior to tumor implantation (long term fish oil) or at the start of chemotherapy (adjuvant fish oil). Chemotherapy (irinotecan plus 5-fluorouracil) was initiated 2 weeks after tumor implantation (cycle-1) and 1 week thereafter (cycle-2). Reference animals received no tumor or treatment and only consumed the control diet. All skeletal muscle measures were conducted in the gastrocnemius. To assess myosteatosis, lipids were assessed histologically by Oil Red O staining and total triglyceride content was quantified by gas chromatography. Expression of adipogenic transcription factors were assessed at the mRNA level by real-time RT-PCR. RESULTS: Feeding a diet containing fish oil significantly reduced tumor- and subsequent chemotherapy-associated increases in skeletal muscle neutral lipid (p<0.001) and total triglyceride content (p<0.03), and expression of adipogenic transcription factors (p<0.01) compared with control diet fed animals. The adjuvant fish oil diet was as effective as the long term fish oil diet in mitigating chemotherapy-associated skeletal muscle fat content, and in reducing tumor volume during chemotherapy compared with control fed animals (p<0.01). CONCLUSION: Long term and adjuvant fish oil diets are equally efficacious in reducing chemotherapy-associated myosteatosis that may be occurring by reducing expression of transcription factors involved in adipogenesis/lipogenesis, and improving tumor-response to chemotherapy in a neoplastic model.