This study explored the effects of different vitamin B5 (VB5) levels on intestinal growth and function of weaned piglets. Twenty-one piglets (7.20 ± 1.11 kg) were included in a 28-day feeding trial with three treatments, including 0 mg/kg (L-VB5), 10 mg/kg (Control) and 50 mg/kg (H-VB5) of VB5 supplement. The results showed that: Large intestine weight/body weight was the highest in H-VB5 group, Control and H-VB5 groups had significantly higher villus height and villus height/crypt depth than the L-VB5 in the ileum (p < .05). Goblet cells (ileal crypt) and endocrine cells (ileal villus) significantly increased in Control and H-VB5 (p < .05). The H-VB5 group exhibited significantly higher levels of ki67 and crypt depth in the cecum and colon, colonic goblet cells and endocrine cells were both rising considerably (p < .05). Isobutyric acid and isovaleric acid were significantly reduced in the H-VB5 group (p < .05), and there was a decreasing trend in butyric acid (p = .073). At the genus level, the relative abundance of harmful bacteria such as Clostridium_Sensu_Structo_1 Strecto_1, Terrisporbacter and Streptococcus decreased significantly and the relative abundance of beneficial bacteria Turicibacter increased significantly in H-VB5 group (p < .05). Overall, the addition of 50 mg/kg VB5 primarily enhanced the morphological structure, cell proliferation and differentiation of the ileum, cecum and colon. It also had a significant impact on the gut microbiota and short-chain fatty acids.

Salt stress negatively affects rice growth, development and yield. Metabolic adjustments contribute to the adaptation of rice under salt stress. Branched-chain amino acids (BCAA) are three essential amino acids that cannot be synthesized by humans or animals. However, little is known about the role of BCAA in response to salt stress in plants. Here, we showed that BCAAs may function as scavengers of reactive oxygen species (ROS) to provide protection against damage caused by salinity. We determined that branched-chain aminotransferase 2 (OsBCAT2), a protein responsible for the degradation of BCAA, positively regulates salt tolerance. Salt significantly induces the expression of OsBCAT2 rather than BCAA synthesis genes, which indicated that salt mainly promotes BCAA degradation and not de novo synthesis. Metabolomics analysis revealed that vitamin B5 (VB5) biosynthesis pathway intermediates were higher in the OsBCAT2-overexpressing plants but lower in osbcat2 mutants under salt stress. The salt stress-sensitive phenotypes of the osbcat2 mutants are rescued by exogenous VB5, indicating that OsBCAT2 affects rice salt tolerance by regulating VB5 synthesis. Our work provides new insights into the enzymes involved in BCAAs degradation and VB5 biosynthesis and sheds light on the molecular mechanism of BCAAs in response to salt stress.

Vitamin B5, also called d-pantothenic acid, is an essential vitamin in the human body and is widely used in pharmaceuticals, nutritional supplements, food, and cosmetics. However, few studies have investigated the microbial production of d-pantothenic acid, especially in Saccharomyces cerevisiae. By employing a systematic optimization strategy, we screened seven key genes in d-pantothenic acid biosynthesis from diverse species, including bacteria, yeast, fungi, algae, plants, animals, etc., and constructed an efficient heterologous d-pantothenic acid pathway in S. cerevisiae. By adjusting the copy number of the pathway modules, knocking out the endogenous bypass gene, balancing NADPH utilization, and regulating the GAL inducible system, a high-yield d-pantothenic acid-producing strain, DPA171, which can regulate gene expression using glucose, was constructed. By optimizing fed-batch fermentation, DPA171 produced 4.1 g/L d-pantothenic acid, which is the highest titer in S. cerevisiae to date. This study provides guidance for the development of vitamin B5 microbial cell factories.

Metabolic rewiring is essential for Th17 cells\' functional identity to sense and interpret environmental cues. However, the environmental metabolic checkpoints with specific regulation of Th17 cells, manifesting potential therapeutic opportunities to autoimmune diseases, remain largely unknown. Here, by screening more than one hundred compounds derived from intestinal microbes or diet, we found that vitamin B5 (VB5) restrains Th17 cell differentiation as well as related autoimmune diseases such as experimental autoimmune encephalomyelitis and colitis. Mechanistically, VB5 is catabolized into coenzyme A (CoA) in a pantothenate kinase (PANK)-dependent manner, and in turn, CoA binds to pyruvate kinase isoform 2 (PKM2) to impede its phosphorylation and nuclear translocation, thus inhibiting glycolysis and STAT3 phosphorylation. In humans, reduced serum VB5 levels are found in both IBD and MS patients. Collectively, our study demonstrates a role of VB5 in Th17 cell metabolic reprograming, thus providing a potential therapeutic intervention for Th17 cell-associated autoimmune diseases.

Vitamin deficiencies are known to cause disorders in human beings. Siddique et al. discovered that vitamin B5 biosynthesis in cyst nematodes requires steps in their host plants. Disruption of an Arabidopsis thaliana \'susceptibility gene\', which is involved in the production of vitamin B5 precursors, results in reduced parasitism.

We aimed to evaluate the prospective association of vitamin B5 with all-cause mortality and explore its potential modifiers in Chinese adults with hypertension. A nested, case-control study was conducted in the China Stroke Primary Prevention Trial, including 505 deaths of all causes and 505 matched controls. The median follow-up duration was 4.5 years. The primary outcome measure in this investigation was all-cause mortality, which encompassed deaths for any reason. The mean plasma vitamin B5 concentration for cases (43.7 ng/mL) was higher than that in controls (40.9 ng/mL) (p = .001). When vitamin B5 was further assessed as quintiles, compared with the reference group (Q1: < 33.0 ng/mL), the risk of all-cause mortality increased by 29% (OR = 1.29, 95% CI: 0.83-2.01) in Q2, 22% (OR = 1.22, 95% CI: 0.77-1.94) in Q3, 62% (OR = 1.62, 95% CI: 1.00-2.62) in Q4, and 77% (OR = 1.77, 95% CI: 1.06-2.95) in Q5. The trend test was significant (p = .022). When Q4-Q5 were combined, a significant 41% increment (OR = 1.41, 95% CI: 1.03-1.95) in all-cause death risk was found compared with Q1-Q3. The adverse effects were more pronounced in those with normal folate levels (p-interaction = .019) and older people (p-interaction = .037). This study suggests that higher baseline levels of plasma vitamin B5 are a risk factor for all-cause mortality among Chinese patients with hypertension, especially among older adults and those with adequate folate levels. The findings, if confirmed, may inform novel clinical and nutritional guidelines and interventions to optimize vitamin B5 levels.

Apostichopus japonicus (sea cucumber) is one of the most valuable aquaculture species in China; however, different diseases can limit its economic development. Recently, a novel disease, body vesicular syndrome (BVS), was observed in A. japonicus aquaculture. Diseased animals displayed no obvious phenotypic characteristics; however, after boiling at the postharvest stage, blisters, lysis, and body ruptures appeared. In this study, a multiomics strategy incorporating analysis of the gut microbiota, the pond microbiome, and A. japonicus genotype was established to investigate BVS. Detailed analyses of differentially expressed proteins (DEPs) and metabolites suggested that changes in cell adhesion structures, caused by disordered fatty acid β-oxidation mediated by vitamin B5 deficiency, could be a putative BVS mechanism. Furthermore, intestinal dysbacteriosis due to microbiome variations in pond water was considered a potential reason for vitamin B5 deficiency. Our BVS index, based on biomarkers identified from the A. japonicus gut microbiota, was a useful tool for BVS diagnosis. Finally, vitamin B5 supplementation was successfully used to treat BVS, suggesting an association with BVS etiology. IMPORTANCE Body vesicular syndrome (BVS) is a novel disease in sea cucumber aquaculture. As no phenotypic features are visible, BVS is difficult to confirm during aquaculture and postharvest activities, until animals are boiled. Therefore, BVS could lead to severe economic losses compared with other diseases in sea cucumber aquaculture. In this study, for the first time, we systematically investigated BVS pathogenesis and proposed an effective treatment for the condition. Moreover, based on the gut microbiota, we established a noninvasive diagnostic method for BVS in sea cucumber.

B vitamins are a class of water-soluble vitamins that play important roles in cell metabolism. The participation of B vitamins in bone health has been recognized for decades. Pantothenic acid (vitamin B5) is mainly known for its wide variety of sources. However, the potential role of pantothenic acid in bone health and metabolism is still unclear. In this study, we found pantothenic acid has a dual effect on RANKL-induced osteoclastogenesis. Tartrate-resistant acid phosphatase (TRAP) stain shows that osteoclastogenesis was remarkably induced in a lower dosage of pantothenic acid (< 200 mM) and significantly inhibited while the pantothenic acid concentration increases to a certain extent (> 500 mM). We further confirmed this dual effect of pantothenic acid in osteoclastogenesis by detecting osteoclast formation and bone resorption using focal adhesion stain and pit formation, respectively. Mechanistically, we found phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt) pathway was activated in pre-osteoclasts (pOCs) after cultured with lower dosage of pantothenic acid; while the ROS generation was eliminated with upregulation of forkhead box O1 (FoxO1), forkhead box O2 (FoxO2) and NF-E2-related factor 2 (Nrf2) in pOCs after cultured with higher dosage of pantothenic acid. Finally, we used ovariectomized (OVX) mice to explore the potential role of pantothenic acid rich dietary in regulating bone metabolism in vivo, the result shows that pantothenic acid rich dietary can protect bone loss from estrogen deficiency. In brief, our study identified a new understanding of pantothenic acid in regulating osteoclastogenesis, revealed a therapeutic potential of pantothenic acid in prevention of bone loss related disorders.

The mechanisms by which vitamins regulate immunity and their effect as an adjuvant treatment for tuberculosis have gradually become very important research topics. Studies have found that vitamin B5 (VB5) can promote epithelial cells to express inflammatory cytokines. We aimed to examine the proinflammatory and antibacterial effect of VB5 in macrophages infected with Mycobacterium tuberculosis (MTB) strain H37Rv and the therapeutic potential of VB5 in vivo with tuberculosis. We investigated the activation of inflammatory signal molecules (NF-κB, AKT, JNK, ERK, and p38), the expression of two primary inflammatory cytokines (tumor necrosis factor and interleukin-6) and the bacterial burdens in H37Rv-infected macrophages stimulated with VB5 to explore the effect of VB5 on the inflammatory and antibacterial responses of macrophages. We further treated the H37Rv-infected mice with VB5 to explore VB5\'s promotion of the clearance of H37Rv in the lungs and the effect of VB5 on regulating the percentage of inflammatory cells. Our data showed that VB5 enhanced the phagocytosis and inflammatory response in macrophages infected with H37Rv. Oral administration of VB5 decreased the number of colony-forming units of H37Rv in lungs of mice at 1, 2, and 4 weeks after infection. In addition, VB5 regulated the percentage of macrophages and promoted CD4+ T cells to express interferon-γ and interleukin-17; however, it had no effect on the percentage of polymorphonuclear neutrophils, CD4+ and CD8+ T cells. In conclusion, VB5 significantly inhibits the growth of MTB by regulating innate immunity and adaptive immunity.

The pantothenate (vitamin B5) synthesis pathway in plants is not fully defined because the subcellular site of its ketopantoate → pantoate reduction step is unclear. However, the pathway is known to be split between cytosol, mitochondria, and potentially plastids, and inferred to involve mitochondrial or plastidial transport of ketopantoate or pantoate. No proteins that mediate these transport steps have been identified. Comparative genomic and transcriptomic analyses identified Arabidopsis thaliana BASS1 (At1g78560) and its maize (Zea mays) ortholog as candidates for such a transport role. BASS1 proteins belong to the bile acid : sodium symporter family and share similarity with the Salmonella enterica PanS pantoate/ketopantoate transporter and with predicted bacterial transporters whose genes cluster on the chromosome with pantothenate synthesis genes. Furthermore, Arabidopsis BASS1 is co-expressed with genes related to metabolism of coenzyme A, the cofactor derived from pantothenate. Expression of Arabidopsis or maize BASS1 promoted the growth of a S. enterica panB panS mutant strain when pantoate, but not ketopantoate, was supplied, and increased the rate of [3H]pantoate uptake. Subcellular localization of green fluorescent protein fusions in Nicotiana tabacum BY-2 cells demonstrated that Arabidopsis BASS1 is targeted solely to the plastid inner envelope. Two independent Arabidopsis BASS1 knockout mutants accumulated pantoate ∼10-fold in leaves and had smaller seeds. Taken together, these data indicate that BASS1 is a physiologically significant plastidial pantoate transporter and that the pantoate reduction step in pantothenate biosynthesis could be at least partly localized in plastids.