Berberine-microbiota interplay: orchestrating gut health through modulation of the gut microbiota and metabolic transformation into bioactive metabolites.

Berberine is an isoquinoline alkaloid found in plants. It presents a wide range of pharmacological activities, including anti-inflammatory and antioxidant properties, despite a low oral bioavailability. Growing evidence suggests that the gut microbiota is the target of berberine, and that the microbiota metabolizes berberine to active metabolites, although little evidence exists in the specific species involved in its therapeutic effects. This study was performed to detail the bidirectional interactions of berberine with the broiler chicken gut microbiota, including the regulation of gut microbiota composition and metabolism by berberine and metabolization of berberine by the gut microbiota, and how they contribute to berberine-mediated effects on gut health. As previous evidence showed that high concentrations of berberine may induce dysbiosis, low (0.1 g/kg feed), middle (0.5 g/kg feed) and high (1 g/kg feed) doses were here investigated. Low and middle doses of in-feed berberine stimulated potent beneficial bacteria from the Lachnospiraceae family in the large intestine of chickens, while middle and high doses tended to increase villus length in the small intestine. Plasma levels of the berberine-derived metabolites berberrubine, thalifendine and demethyleneberberine were positively correlated with the villus length of chickens. Berberrubine and thalifendine were the main metabolites of berberine in the caecum, and they were produced in vitro by the caecal microbiota, confirming their microbial origin. We show that members of the genus Blautia could demethylate berberine into mainly thalifendine, and that this reaction may stimulate the production of short-chain fatty acids (SCFAs) acetate and butyrate, via acetogenesis and cross-feeding respectively. We hypothesize that acetogens such as Blautia spp. are key bacteria in the metabolization of berberine, and that berberrubine, thalifendine and SCFAs play a significant role in the biological effect of berberine.

A High Dose of Dietary Berberine Improves Gut Wall Morphology, Despite an Expansion of Enterobacteriaceae and a Reduction in Beneficial Microbiota in Broiler Chickens.

Phytogenic products are embraced as alternatives to antimicrobials, and some are known to mitigate intestinal inflammation and ensure optimal gut health and performance in broiler chickens. Dietary inclusion of berberine, a benzylisoquinoline alkaloid found in plants, is believed to exert gut health-promoting effects through modulation of the gut microbiota; however, there are only a few studies investigating its effects in chickens. The aim of this study was to investigate the interplay between dietary supplementation of a high concentration of berberine, the gastrointestinal microbiota, and histomorphological parameters in the gut. Berberine was shown to increase villus length and decrease crypt depth and CD3+ T-lymphocyte infiltration in the gut tissue of chickens at different ages. Berberine affected the diversity of the gut microbiota from the jejunum to the colon, both at a compositional and functional level, with larger effects observed in the large intestine. A high concentration of berberine enriched members of the Enterobacteriaceae family and depleted members of the Ruminococcaceae, Lachnospiraceae, and Peptostreptococcaceae families, as well as tended to reduce butyrate production in the cecum. In vivo results were confirmed by in vitro growth experiments, where increasing concentrations of berberine inhibited the growth of several butyrate-producing strains while not affecting that of Enterobacteriaceae strains. Positive correlations were found between berberine levels in plasma and villus length or villus-to-crypt ratio in the jejunum. Our study showed that berberine supplementation at a high concentration improves chicken gut morphology toward decreased inflammation, which is likely not mediated by the induced gut microbiota shifts. IMPORTANCE Dietary additives are widely used to reduce intestinal inflammation and enteritis, a growing problem in the broiler industry. Berberine, with anti-inflammatory, antioxidant, and antimicrobial activity, would be an interesting feed additive in this regard. This study investigates for the first time the impact of berberine supplementation on the chicken gastrointestinal microbiota, as a potential mechanism to improve gut health, together with histological effects in the small intestine. This study identified a dose-effect of berberine on the gut microbiota, indicating the importance of finding an optimal dose to be used as a dietary additive.

Omics technologies in poultry health and productivity - part 2: future applications in the poultry industry.

The increasing global demand for poultry products, together with the growing consumer concerns related to bird health and welfare, pose a significant challenge to the poultry industry. Therefore, the poultry industry is increasingly implementing novel technologies to optimize and enhance bird welfare and productivity. This second part of a bipartite review on omics technologies in poultry health and productivity highlights the implementation of specific diagnostic biomarkers based on omics-research in the poultry industry, as well as the potential integration of multi-omics in future poultry production. A general discussion of the use of multiple omics technologies in poultry research is provided in part 1. To date, approaches focusing on one or more omics type are widely used in poultry research, but the implementation of these omics techniques in poultry production is not expected in the near future. However, great potential lays in the development of diagnostic tests based on disease- or gut health-specific biomarkers, which are identified through omics research. As the cost of omics technologies is rapidly decreasing, implementation of multi-omics measurements in routine poultry monitoring systems might be feasible in the more distant future. Therefore, the opportunities, challenges and requirements to enable the integration of multi-omics-based monitoring of bird health and productivity in future poultry production are discussed.

Omics technologies in poultry health and productivity - part 1: current use in poultry research.

In biology, molecular terms with the suffix "-omics" refer to disciplines aiming at the collective characterization of pools of molecules derived from different layers (DNA, RNA, proteins, metabolites) of living organisms using high-throughput technologies. Such omics analyses have been widely implemented in poultry research in recent years. This first part of a bipartite review on omics technologies in poultry health and productivity examines the use of multiple omics and multi-omics techniques in poultry research. More specific present and future applications of omics technologies, not only for the identification of specific diagnostic biomarkers, but also for potential future integration in the daily monitoring of poultry production, are discussed in part 2. Approaches based on omics technologies are particularly used in poultry research in the hunt for genetic markers of economically important phenotypical traits in the host, and in the identification of key bacterial species or functions in the intestinal microbiome. Integrative multi-omics analyses, however, are still scarce. Host physiology is investigated via genomics together with transcriptomics, proteomics and metabolomics techniques, to understand more accurately complex production traits such as disease resistance and fertility. The gut microbiota, as a key player in chicken productivity and health, is also a main subject of such studies, investigating the association between its composition (16S rRNA gene sequencing) or function (metagenomics, metatranscriptomics, metaproteomics, metabolomics) and host phenotypes. Applications of these technologies in the study of other host-associated microbiota and other host characteristics are still in their infancy.