Prophylactic Effect of Bovine Colostrum on Intestinal Microbiota and Behavior in Wild-Type and Zonulin Transgenic Mice

Abstract

The microbiota–gut–brain axis (MGBA) involves bidirectional communication between intestinal microbiota and the gastrointestinal (GI) tract, central nervous system (CNS), neuroendocrine/neuroimmune systems, hypothalamic–pituitary–adrenal (HPA) axis, and enteric nervous system (ENS). The intestinal microbiota can influence host physiology and pathology. Dysbiosis involves the loss of beneficial microbial input or signal, diversity, and expansion of pathobionts, which can lead to loss of barrier function and increased intestinal permeability (IP). Colostrum, the first milk from mammals after birth, is a natural source of nutrients and is rich in oligosaccharides, immunoglobulins, growth factors, and anti-microbial components. The aim of this study was to investigate if bovine colostrum (BC) administration might modulate intestinal microbiota and, in turn, behavior in two mouse models, wild-type (WT) and Zonulin transgenic (Ztm)—the latter of which is characterized by dysbiotic microbiota, increased intestinal permeability, and mild hyperactivity—and to compare with control mice. Bioinformatics analysis of the microbiome showed that consumption of BC was associated with increased taxonomy abundance (p = 0.001) and diversity (p = 0.004) of potentially beneficial species in WT mice and shifted dysbiotic microbial community towards eubiosis in Ztm mice (p = 0.001). BC induced an anxiolytic effect in WT female mice compared with WT female control mice (p = 0.0003), and it reduced anxiogenic behavior in Ztm female mice compared with WT female control mice (p = 0.001), as well as in Ztm male mice compared with WT BC male mice (p = 0.03). As evidenced in MGBA interactions, BC supplementation may well be applied for prophylactic approaches in the future. Further research is needed to explore human interdependencies between intestinal microbiota, including eubiosis and pathobionts, and neuroinflammation, and the potential value of BC for human use. The MGH Institutional Animal Care and Use Committee authorized the animal study (2013N000013).

Bovine Colostrum Supplementation Modulates the Intestinal Microbial Community in Rabbits

“…In particular, the microbiota’s biodiversity in the caecum mucosa tended to increase as the dose of BC supplementation increased. Similar results were found after BC administration on mice’s gut microbiota, mainly due to an increase in short-chain fatty acids-producing microorganisms [ 57 ]. In the same investigation, the effect of BC administration was also found for the microbial composition evaluated by beta-diversity analysis.…”

“…Lachnospiraceae are among the main producers of short-chain fatty acids in the gut microbiota, particularly butyrate, which is among the main energetic sources for colonocytes, while Akkermansiaceae metabolize the mucin present in the mucus gel layer in the colon tract. As hypothesized in another study evaluating the effect of bovine colostrum feed supplementation on mice [ 57 ], the increase of Lachnospiraceae and Akkermansiaceae could have a positive effect at multiple levels, such as on the intestinal barrier, on the nervous system development, and on the immune system of the host. Finally, the Bacteroidaceae family provides nutrients and vitamins to the organism through the metabolization of polysaccharides and oligosaccharides, and, as a consequence, it is considered beneficial for the intestinal microbiota [ 66 ].…”

Understanding the Immunomodulatory Effects of Bovine Colostrum: Insights into IL-6/IL-10 Axis-Mediated Inflammatory Control

“…The rich composition of biologically active substances in COL, including vital nutrients, growth factors, and immunoglobulins, orchestrates the maturation of the intestinal mucosa and shapes the immunological milieu at both local and systemic levels [ 30 ]. Notably, COL has been found to influence the microbiome of calves, suggesting a potential interplay between colostrum, the microbiome, and mucosal immune responses that contribute to intestinal homeostasis, tolerance, and protection against diarrheal diseases [ 31 ]. Despite the well-documented observations regarding the beneficial effects of COL on calf health and development, there remains a significant knowledge gap concerning the specific molecular pathways regulated by colostrum that underlie its beneficial effects on the intestinal environment and innate immune responses [ 32 , 33 , 34 ].…”

Microbiome: The Next Frontier in Psychedelic Renaissance

“…The ENS is a complex network that controls intrinsic gut functions like motility, secretion, and absorption. Multiple pathways such as the ANS, ENS, HPA axis, immune, endocrine, and neural pathways influence communication between the gut and brain [ 33 , 34 , 35 ]. The ENS communicates with the central nervous system (CNS) via intestinofugal neurons, and sensory information travels via primary afferent neurons.…”