Inflammatory bowel disease (IBD) is associated with gut dysbiosis and can lead to colitis-associated malignancies. Bacteroides uniformis (Bu) regulates animal intestinal homeostasis; however, the mechanism by which it alleviates colitis in mice remains unknown. We investigated the effects of B. uniformis JCM5828 and its metabolites on female C57BL/6J mice with dextran sulfate sodium salt (DSS) induced colitis. Treatment with Bu considerably alleviated colitis progression and restored the mechanical and immune barrier protein expression. Additionally, Bu increased the abundance of the symbiotic bacteria Bifidobacterium and Lactobacillus vaginalis while decreasing that of pathogenic Escherichia-Shigella, and modulated intestinal bile acid metabolism. Bu largely regulated the expression of key regulatory proteins of the NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways in colonic tissues and the differentiation of TH17 cells. However, Bu could not directly inhibit TH17 cell differentiation in vitro; it modulated the process in the lamina propria by participating in bile acid metabolism and regulating key metabolites (alpha-muricholic, hyodeoxycholic, and isolithocholic acid), thereby modulating the intestinal immune response. Our findings suggest that Bu or bile acid supplements are potential therapies for colitis and other diseases associated with intestinal barrier dysfunction.

Trace elements are essential dietary components for livestock species. However, they also exhibit a strong toxic potential. Therefore, their fluxes through the animal organism are tightly regulated by a complex molecular machinery that controls the rate of absorption from the gut lumen as well as the amount of excretion via faeces, urine and products (e.g., milk) in order to maintain an internal equilibrium. When supplemented in doses above the gross requirement trace elements accumulate in urine and faeces and, hence, manure. Thereby, trace element emissions represent a potential threat to the environment. This fact is of particular importance in regard to the widely distributed feeding practice of pharmacological zinc and copper doses for the purpose of performance enhancement. Adverse environmental effects have been described, like impairment of plant production, accumulation in edible animal products and the water supply chain as well as the correlation between increased trace element loads and antimicrobial resistance. In the light of discussions about reducing the allowed upper limits for trace element loads in feed and manure from livestock production in the European Union excessive dosing needs to be critically reconsidered. Moreover, the precision in trace element feeding has to be increased in order to avoid unnecessary supplementation and, thereby, heavy metal emissions from livestock production.

Sufficient zinc (Zn) supply is a key element of successful animal husbandry. Proper use of dietary Zn sources, however, demands knowledge of Zn requirement and bioavailability, reflecting practical feeding systems. In this study, an experimental model is presented where 48 fully weaned and individually housed piglets received a fine differentiated alimentary Zn supply. The basal diet consisted mainly of corn and soybean meal (native Zn: 28.1 mg/kg feed) and was fortified with Zn from Zn sulphate at eight levels (0, 5, 10, 15, 20, 30, 40 and 60 mg Zn/kg). All animals were pretreated uniformly with the highest Zn supply (88 mg total Zn/kg feed) for two weeks (feeding ad libitum). Subsequently, animals were switched to the eight experimental diets (six animals per group, restricted feeding at 450 g/d). This period was limited to 8 d in order to avoid clinical Zn-deficiency symptoms. Measurements included amounts of apparently digested Zn, final levels of plasma Zn, plasma Zn-binding capacity, plasma alkaline phosphatase activity, femur Zn, liver Zn as well as hepatic metallothionein (Mt) 1a and Mt2b gene expression and hepatic Mt protein abundance. Clinical signs of Zn deficiency were completely absent through the entire study. All the analysed parameters except for Mt protein abundance responded sensitively to graduations in dietary Zn contents and indicated the presence of Zn deficiency at lower dietary Zn additions. Amounts of apparently digested Zn, liver Zn as well as hepatic Mt1a and Mt2b gene expression indicated transition from deficient to sufficient Zn supply between 47.5 and 58.2 mg of total Zn per kg of diet as assessed by broken-line response techniques. Analysed blood and bone parameters responded linearly to graduations in dietary Zn supply even within sufficient Zn supply levels. Taken together, the results indicate the suitability of our experimental model to determine Zn requirement in piglets and hence to also assess bioavailability of dietary Zn sources. The latter may be done by comparing the slope of the amounts of apparently digested Zn as well as by determining the response of blood and bone parameters to graduations in dietary Zn at insufficient Zn supply.

Early weaning induces intestinal injury, leading to a series of long-term symptoms such as inflammation, malabsorption and diarrhea. In this study, we hypothesized that microbes and their metabolites modulate the host's inflammatory response to early weaning stress in a goat model. A total of 18 female Tibetan goat kids (n = 9) were weaned from their mothers at 28 d (D28) and 60 d (D60) postpartum. D60 and D28 groups were fed the same solid diet ad libitum from weaning to 75 d of age. The colonic epithelium was subject to RNA-sequencing, the caecal digesta metabolomics were assessed by liquid chromatography–tandem mass spectrometry (LC-MS/MS), and the caecal microbiota composition was analysed by 16S ribosomal RNA gene sequencing. We found that early weaning substantially increased the colonic pro-apoptotic gene expression of B-cell lymphoma associated X (Bax), caspase-9, and caspase-3, and decreased the expression of zonula occludens-1 (ZO-1) and claudin-1 (P < 0.01). In addition, a significant Bacteroides acidifaciens enrichment was observed in the hindgut of early-weaned goats (P < 0.01), which negatively correlated with lysophosphatidylcholine products. Similarly, the chemokine signaling, IL-17 signaling, and peroxisome proliferators-activated receptor (PPAR) signaling pathways were upregulated in the colonic mucosa of the early-weaned goats. By applying caecal microbiota transplantation from goats to defaunated C57/6J mice, we confirmed that caecal microbiota of D28 goat kids increased the relative abundance of B. acidifaciens and significantly up-regulated the genes of Bax, G protein–coupled receptor (GPR) 109A, GPR 43, fatty acid binding protein 6, nuclear receptor subfamily 1 group H member 3, angiotensin converting enzyme 2, and IL-6 expression (P < 0.05), and decreased ZO-1, and claudin-1 protein expression in the mice jejunum and colon (P < 0.001). These results proposed that the hindgut microbiota and metabolites mediate the barrier function weakening during early weaning, and the relative abundance of B. acidifaciens was negatively correlated with the hindgut barrier gene expression. This study demonstrates how weaning stress can affect key host–microbe interaction regulators in the hindgut, in a lysophosphatidylcholine dependent and independent manner. Furthermore, based on our mice data, these results are transferable to other mammal species.

Practical diets for monogastric livestock must be supplemented with zinc (Zn) due to their high contents of antagonistic substances like phytates. Current feeding recommendations include quite generous safety margins because of uncertainties regarding the gross Zn requirements under varying rearing conditions. Furthermore, the use of pharmacological Zn doses to stabilise animal performance and wellbeing is widespread. Taken together, modern diets for pigs and poultry contain considerably more Zn than necessary to meet animal requirements, which is associated with concerns related to the environment as well as animal and consumer safety. Therefore, European authorities most recently reduced the allowed upper limits for Zn in complete feed. To maintain animal productivity and wellbeing while reducing the Zn load in complete feed, all measures that stabilize feed Zn bioavailability must be applied. Most importantly, reliable information on the gross Zn requirement under practical conditions must be provided, considering the bioavailability of native or supplemented feed Zn, antagonisms with dietary factors as well as the physiological status of the animal.

Currently, the authorisation procedure of trace elements as feed additives in the European Union according to Regulation (EC) No. 1831/2003 does not consider the bioavailability of trace element sources. This manuscript provides framework conditions for in vivo experiments that aim to estimate differences in the relative bioavailability between supplements of essential trace elements. Framework conditions encompass necessary technical information on the test substance, the experimental design and diet composition as well as the suitability of status parameters that allow for relative comparisons of regression variables. This manuscript evolves recommendations for researchers to conduct solid and reliable experiments on the matter as well as decision makers to interpret the value of studies submitted with authorisation applications regarding a certain trace element supplement.