Biology subjects

Andersen-Civil, A.

Publications and source records attributed to Andersen-Civil, A..

4 recordsLinked to original sources

bioRxiv2023

Diet composition drives tissue-specific intensity of murine enteric infections

Diet composition plays a large role in regulating of gut health and enteric infection. In particular, synthetic Western-style diets may predispose to disease, whilst whole-grain diets containing high levels of crude fiber are thought to promote gut health. Here we show that, in contrast to this paradigm, mice fed unrefined chow are significantly more susceptible to infection with Trichuris muris, a caecum-dwelling nematode, than mice given refined, semi-synthetic diets (SSD). Moreover, mice fed SSD supplemented with inulin, a fermentable fiber, developed chronic T. muris burdens whereas mice given SSD efficiently cleared the infection. Diet composition significantly impacted infection-induced changes in the host gut microbiome. Mice infected with the bacterium Citrobacter rodentium were also more susceptible to pathogen colonization when fed either chow or inulin-enriched SSD. However, transcriptomic analysis of tissues from mice fed either SSD or inulin-enriched SSD revealed that, in contrast to T. muris, increased C. rodentium infection appeared to be independent of the host immune response. Accordingly, exogenous treatment with IL-25 partially reduced T. muris burdens in inulin-fed mice, whereas IL-22 treatment was unable to restore resistance to C. rodentium colonization. Diet-mediated effects on pathogen burden were more pronounced for large intestine-dwelling pathogens, as effects on small intestinal helminth (Heligmosomoides polygyrus) were less evident, and protozoan (Giardia muris) infection burdens were equivalent in mice fed chow, inulin-enriched SSD, or SSD, despite higher cyst excretion in chow-fed mice. Collectively, our results point to a tissue- and pathogen-restricted effect of dietary fiber levels on enteric infection intensity. ImportanceEnteric infections induce dysbiosis and inflammation and are a major public health burden. As the gut environment is strongly shaped by diet, the role of different dietary components in promoting resistance to infection is of interest. Whilst diets rich in fiber or whole grain are normally associated with improved gut health, we show here that these components predispose the host to higher levels of pathogen infection. Thus, our results have significance for interpreting how different dietary interventions may impact on gastrointestinal infections. Moreover, our results may shed light on our understanding of how gut flora and musical immune function is influenced by the food that we eat.

microbiology↗

bioRxiv2021

Garlic-derived organosulfur compounds regulate metabolic and immune pathways in macrophages and attenuate intestinal inflammation in mice

ScopeGarlic is a source of bioactive phytonutrients that may have anti-inflammatory or immunomodulatory properties. The mechanism(s) underlying the bioactivity of these compounds and their ability to regulate responses to enteric infections remains unclear. Methods and ResultsWe investigated if a garlic-derived preparation (PTSO-PTS) containing two organosulfur metabolites, propyl-propane thiosulfonate (PTSO) and propyl-propane thiosulfinate (PTS), regulated inflammatory responses in murine macrophages and intestinal epithelial cells (IEC) in vitro, as well as in a model of enteric parasite-induced inflammation. PTSO-PTS decreased lipopolysaccharide-induced secretion of TNF, IL-6 and IL-27 in macrophages. RNA-sequencing demonstrated that PTSO-PTS strongly suppressed pathways related to immune and inflammatory signaling. PTSO-PTS induced the expression of a number of genes involved in antioxidant responses in IEC during exposure to antigens from the parasite Trichuris muris. In vivo, PTSO-PTS did not affect T. muris establishment or intestinal T-cell responses but significantly altered caecal transcriptomic responses. Notably, a reduction in T. muris-induced expression of Tnf, Saa2 and Nos2 was observed. ConclusionGarlic-derived organosulfur compounds exert anti-inflammatory effects in macrophages and IEC, and regulate gene expression during intestinal infection. These compounds and related organic molecules may thus hold potential as functional food components to improve gut health in humans and animals.

immunology↗

bioRxiv2021

Structure-function analysis of purified proanthocyanidins reveals a role for polymer size in suppressing inflammatory responses

Proanthocyanidins (PAC) are dietary compounds that have been extensively studied for beneficial health effects due to their anti-inflammatory properties. However, the structure-function relationships of PAC and their mode-of-action remain obscure. Here, we isolated a wide range of diverse PAC polymer mixtures of unprecedented purity from plant material. Polymer size was a key factor in determining the ability of PAC to regulate inflammatory cytokine responses in murine macrophages. PAC polymers with a medium (9.1) mean degree of polymerization (mDP) induced substantial transcriptomic changes, whereas PAC with either low (2.6) or high (12.3) mDP were significantly less active. Short-term oral treatment of mice with PAC modulated gene pathways connected to nutrient metabolism and inflammation in ileal tissue in a polymerization-dependent manner. Mechanistically, the bioactive PAC polymers modulated autophagic flux and directly inhibited lipopolysaccharide-induced autophagy. Collectively, our results highlight the importance of defined structural features in the health-promoting effects of PAC-rich foods.

immunology↗

bioRxiv2021

The phytonutrient cinnamaldehyde limits intestinal inflammation and enteric parasite infection

Phytonutrients such as cinnamaldehyde (CA) have been studied for their effects on metabolic diseases, but their influence on mucosal inflammation and immunity to enteric infection are not well documented. Here, we show that consumption of CA significantly down-regulates transcriptional pathways connected to inflammation in the small intestine of mice. During infection with the enteric helminth Heligomosomoides polygyrus, CA-treated mice displayed higher growth rates and less worms, concomitant with altered T-cell populations in mesenteric lymph nodes. Furthermore, infection-induced changes in gene pathways connected to cell cycle and mitotic activity were counteracted by CA. Mechanically, CA did not appear to exert activity through a prebiotic effect, as CA treatment did not significantly change the composition of the gut microbiota. Instead, in vitro experiments showed that CA directly induced xenobiotic metabolizing pathways in intestinal epithelial cells and suppressed endotoxin-induced inflammatory responses in macrophages. Thus, CA down-regulates inflammatory pathways in the intestinal mucosa and regulates host responses to enteric infection. These properties appear to be largely independent of the gut microbiota and instead connected to CAs ability to induce antioxidant pathways in intestinal cells. Our results encourage further investigation into the use of CA and related phytonutrients as functional food components to promote intestinal health in humans and animals.

immunology↗