Impact of Bacillus licheniformis from yaks following antibiotic therapy in mouse model.

Gut microorganism (GM) is an integral component of the host microbiome and health system. Abuse of antibiotics disrupts the equilibrium of the microbiome, affecting environmental pathogens and host-associated bacteria alike. However, relatively little research on Bacillus licheniformis alleviates the adverse effects of antibiotics. To test the effect of B. licheniformis as a probiotic supplement against the effects of antibiotics, cefalexin was applied, and the recovery from cefalexin-induced jejunal community disorder and intestinal barrier damage was investigated by pathology, real-time PCR (RT-PCR), and high-throughput sequencing (HTS). The result showed that A group (antibiotic treatment) significantly reduced body weight and decreased the length of jejunal intestinal villi and the villi to crypt (V/C) value, which also caused structural damage to the jejunal mucosa. Meanwhile, antibiotic treatment suppressed the mRNA expression of tight junction proteins ZO-1, claudin, occludin, and Ki67 and elevated MUC2 expression more than the other Groups (P < 0.05 and P < 0.01). However, T group (B. licheniformis supplements after antibiotic treatment) restored the expression of the above genes, and there was no statistically significant difference compared to the control group (P > 0.05). Moreover, the antibiotic treatment increased the relative abundance of 4 bacterial phyla affiliated with 16 bacterial genera in the jejunum community, including the dominant Firmicutes, Proteobacteria, and Cyanobacteria in the jejunum. B. licheniformis supplements after antibiotic treatment reduced the relative abundance of Bacteroidetes and Proteobacteria and increased the relative abundance of Firmicutes, Epsilonbacteraeota, Lactobacillus, and Candidatus Stoquefichus. This study uses mimic real-world exposure scenarios by considering the concentration and duration of exposure relevant to environmental antibiotic contamination levels. We described the post-antibiotic treatment with B. licheniformis could restore intestinal microbiome disorders and repair the intestinal barrier. KEY POINTS: • B. licheniformis post-antibiotics restore gut balance, repair barrier, and aid health • Antibiotics harm the gut barrier, alter structure, and raise disease risk • Long-term antibiotics affect the gut and increase disease susceptibility.

Gut microbiota and metabolic modulation by supplementation of polysaccharide-producing Bacillus licheniformis from Tibetan Yaks: A comprehensive multi-omics analysis.

Gut microbiota and their metabolic processes depend on the intricate interplay of gut microbiota and their metabolic processes. Bacillus licheniformis, a beneficial food supplement, has shown promising effects on stabilizing gut microbiota and metabolites. However, the precise mechanisms underlying these effects remain elusive. In this study, we investigated the impact of polysaccharide-producing B. licheniformis as a dietary supplement on the gut microbiome and metabolites through a combination of scanning electron microscopy (SEM), histological analysis, high-throughput sequencing (HTS), and metabolomics. Our findings revealed that the B. licheniformis-treated group exhibited significantly increased jejunal goblet cells. Moreover, gut microbial diversity was lower in the treatment group as compared to the control, accompanied by noteworthy shifts in the abundance of specific bacterial taxa. Enrichment of Firmicutes, Lachnospiraceae, and Clostridiales_bacterium contrasted with reduced levels of Campylobacterota, Proteobacteria, Parasutterella, and Helicobacter. Notably, the treatment group showed significant weight gain after 33 days, emphasizing the polysaccharide's impact on host metabolism. Delving into gut metabolomics, we discovered significant alterations in metabolites. Nine metabolites, including olprinone, pyruvic acid, and 2-methyl-3-oxopropanoate, were upregulated, while eleven, including defoslimod and voclosporin were down-regulated, shedding light on phenylpropanoid biosynthesis, tricarboxylic acid cycle (TCA cycle), and the glucagon signaling pathway. This comprehensive multi-omics analysis offers compelling insights into the potential of B. licheniformis as a dietary polysaccharide supplement for gut health and host metabolism, promising significant implications for gut-related issues.

Hedyotis diffusa alleviate aflatoxin B1-induced liver injury in ducks by mediating Nrf2 signaling pathway.

Aflatoxin B1 (AFB1), the most harmful aflatoxins, is a frequent contamination in feed and food items, raising global concerns in animal production and human public health. Also, AFB1 induces oxidative stress, cytotoxicity, mutations, and DNA lesions through its metabolic transformation into aflatoxin B1-8,9-epoxide (AFBO) by cytochrome P450 (CYP450). Hedyotis diffusa (HD) is a traditional Chinese herbal medicine known for its multiple pharmacological activities, including antioxidant, anti-inflammatory, and immunomodulatory. Yet, the influence of HD on AFB1-induced liver injury in ducks is still unknown. Here, we investigated whether HD positively affects AFB1-induced liver injury in ducks. Results revealed that I) AFB1 caused significant changes in serum biochemical indices and decreased growth performance of ducks (such as ALT, AST, ALP, TP, ALB, final body weight, and body weight gain), whereas HD supplementation at 200 mg/kg mitigated these alterations. II) HD alleviated hepatic histopathological changes and liver index induced by AFB1 in ducks. III) HD significantly attenuated AFB1-induced oxidative stress, as measured by increased antioxidant enzyme activities such as SOD, GPx, and T-AOC and decreased MDA levels. Furthermore, HD reduced the level of AFB1-DNA adduct in duck liver. IV) HD significantly promoted the transcriptional expression of NF-E2-related nuclear factor 2 (Nrf2) and associated genes, including heme oxygenase 1 (HO-1), NAD(P)H dehydrogenase quinone 1 (NQO1), glutamate-cysteine ligase catalytic (GCLC). In conclusion, these results demonstrated that HD could activate the Nrf2 pathway in ducks to reduce the hepatotoxicity driven by AFB1. This finding also provides theoretical and data support for a deeper understanding of the toxic mechanisms of AFB1 and its prevention.

Chlorogenic acid suppresses miR-460a in the regulation of Bcl-2, causing interleukin-1ß reduction in thiram exposed chondrocytes via caspase-3/caspase-7 pathway.

BACKGROUND: Apoptosis is thought to be involved in all processes, including normal cell cycle, immune system, atrophy, embryonic development, and chemical-induced cellular damage. However, if the normal apoptotic process fails, the results might be disastrous, e.g., chondrocytes damage in tibial dyschondroplasia (TD). TD is a worldwide issue in the poultry sector due to thiram toxicity. Thiram (Tetramethyl thiuram disulfide) is a dithiocarbamate pesticide and fungicide commonly used in horticulture to treat grains meant for seed protection and preservation. PURPOSE: According to prior studies, chlorogenic acid (CGA) is becoming essential for regulating apoptosis. But still, the specific role of CGA in chondrocyte cells remains unclear. The present study explored the molecular mechanism of CGA on chondrocytes' apoptosis with B-cell lymphoma 2 signaling under the effect of miR-460a. METHODS: An in vivo and in vitro study was performed according to our previously developed methodology. Flow cytometry, western blotting, reverse transcription-quantitative polymerase chain reaction, and immunofluorescence assay were used to investigate the involvement of apoptosis and inflammasome related pathways. RESULTS: The CGA decreased the apoptosis rate with the deactivation of miR-460a, accompanied by the activation of Bcl-2. The high expression of miR-460a reduced the cell viability of chondrocytes in vitro and in vivo, that led to the interleukin-1ß production. While the apoptotic executioners (caspase-3 and caspase-7) acted upstream in miR-460a overexpressing cells, and its depletion downgraded these executioners. The CGA administrated cells negatively regulated miR-460a expression and thus indicating the deactivation of the apoptotic and inflammasome related pathways. CONCLUSION: Chlorogenic acid had a negative effect on miR-460a, setting off specific feedback to regulate apoptotic and inflammasome pathways, which might be a key feature for chondrocytes' survival.

Effects of Milk Replacer-Based Lactobacillus on Growth and Gut Development of Yaks' Calves: a Gut Microbiome and Metabolic Study.

The gut microbiota and its metabolic activities are crucial for maintaining host homoeostasis and health, of which the role of probiotics has indeed been emphasized. The current study delves into the performance of probiotics as a beneficial managemental strategy, which further highlights their impact on growth performance, serologic investigation, gut microbiota, and metabolic profiling in yaks' calves. A field experiment was employed consisting of 2 by 3 factorial controls, including two development stages, namely, 21 and 42 days (about one and a half month), with three different feeding treatments. Results showed a positive impact of probiotic supplements on growth performance by approximately 3.16 kg (P < 0.01) compared with the blank control. Moreover, they had the potential to improve serum antioxidants and biochemical properties. We found that microorganisms that threaten health were enriched in the gut of the blank control with the depletion of beneficial bacteria, although all yaks were healthy. Additionally, the gut was colonized by a microbial succession that assembled into a more mature microbiome, driven by the probiotics strategy. The gut metabolic profiling was also changed significantly after the probiotic strategy, i.e., the concentrations of metabolites and the metabolic pattern, including enrichments in protein digestion and absorption, vitamin digestion and absorption, and biosynthesis of secondary metabolites. In summary, probiotics promoted gut microbiota/metabolites, developing precise interventions and achieving physiological benefits based on intestinal microecology. Hence, it is important to understand probiotic dietary changes to the gut microbiome, metabolome, and the host phenotype. IMPORTANCE The host microbiome is a composite of the trillion microorganisms colonizing host bodies. It can be impacted by various factors, including diet, environmental conditions, and physical activities. The yaks' calves have a pre-existing imbalance in the intestinal microbiota with an inadequate feeding strategy, resulting in poor growth performance, diarrhea, and other intestinal diseases. Hence, targeting gut microbiota might provide a new effective feeding strategy for enhancing performance and maintaining a healthy intestinal environment. Based on the current findings, milk replacer-based Lactobacillus feeding may improve growth performance and health in yaks' calves.

Milk replacer supplementation in early life optimizes the development of intestinal microbes in goats.

Colonization and development of the gut microbiome during early life is important in establishing a host-microbial symbiotic relationship. It contributes to maintaining health and well-being throughout the life span. To date, early longitudinal development of intestinal microflora in the ileum micro-ecology of the Yimeng black goats (YBGs) is rare. The purpose of this research was to study the effect of milk replacer with age on the ileal microbiota growth and maturation in YBGs throughout the post-weaning phase. The newborn YBGs (n = 24) were divided into two groups, i.e., milk replacer (R group) and control group (B group). The microbiome of Ileum was observed on days 15, 25, 45, and 75. When compared with baseline (B group), the R group's alpha diversity was lower (day 15, 25, 45), but it gradually approached and exceeded the baseline in the later stages (day 75). On the time axis, the richness of intestinal microflora was increased with age, but there was no statistically significant difference. The relative abundances of Proteobacteria, Firmicutes, Peptoclustridium, Lachnospiraceae, and Prevotellaceae showed a continuous trend of increase initially. They then decreased except Ruminococcaceae, which reflected the gradual maturity of intestinal microbial development. Milk replacer treatment temporarily increased the abundance of Actinomycetes (day 25 and 45), while the relative proportion of several intestinal bacteria such as Parasutterella, Megasphaera, Prevotellaceae, Akkermansia, and Subdoligranulum species were significantly higher in R group than in B group. The major changes in gut microflora composition might reflect positive effect of milk replacer on the development and maturation of the intestine during the early stage, connecting with substrate availability in the gut. Our study provides an effective strategy to promote the development of the gut microbiome, which is helpful for a smooth transition during the early-weaning period in YBGs.

Potential influence of Nagella sativa (Black cumin) in reinforcing immune system: A hope to decelerate the COVID-19 pandemic.

The world is witnessing a difficult time. The race of developing a new coronavirus (COVID-19) vaccine is becoming more urgent. Many preliminary studies on the pathophysiology of COVID-19 patients have provided some clues to treat this pandemic. However, no suitable treatment has found yet. Various symptoms of patients infected with COVID-19 indicated the importance of immune regulation in the human body. Severe cases admitted to the intensive care unit showed high level of pro-inflammatory cytokines which enhanced the disease severity. Acute Respiratory Distress Syndrome (ARDS) in COVID-19 patients is another critical factor of disease severity and mortality. So, Immune modulation is the only way of regulating immune system. Nigella sativa has been used for medicinal purposes for centuries. The components of this plant are known for its intense immune-regulatory, anti-inflammatory, and antioxidant benefits in obstructive respiratory disorders. A molecular docking study also gave evidences that N. sativa decelerates COVID-19 and might give the same or better results than the FDA approved drugs. The aim of this review was to investigate the possible immune-regulatory effects of N. sativa on COVID-19 pandemic. Our review found N. sativa's Thymoquinone, Nigellidine, and α-hederin can be a potential influencer in reinforcing the immune response on molecular grounds.