Pancytopenia is a complex medical condition characterized by decreased levels of red blood cells (RBCs), white blood cells (WBCs), and platelets (PLTs). It can arise from impaired production, peripheral destruction, or a combination of both. The causes of pancytopenia range from reversible factors like infections and medication reactions to irreversible conditions. Vitamin B12 deficiency is a notable reversible cause that can take years to manifest in adults due to stored reserves. However, deficiencies caused by impaired absorption, especially due to the lack of intrinsic factors (IFs), can lead to rapid deterioration within two to five years. A healthy 39-year-old male with an athletic lifestyle presented with symptoms such as dizziness, nausea, vomiting, palpitations, and fainting over a few days. These symptoms were preceded by weeks of persistent body aches, headaches, weakness, daily fevers, chills, and night sweats. Vital signs were stable. The physical examination revealed conjunctival pallor and lymphadenopathy in the submandibular and superficial cervical regions. Initial blood tests showed normocytic anemia (Hgb 4.9, MCV 80), leukopenia (2.99), thrombocytopenia (142), and elevated liver enzymes (AST 199, ALT 96, and total bilirubin of 2.04). The peripheral smear showed tear-drop cells and hypochromic cells. The initial impression was hematologic malignancy, including but not limited to leukemia, lymphoma, or myelofibrosis given clinical findings such as B-symptoms like night sweats, neck lymphadenopathy, and subjective daily fever, along with pancytopenia. The patient received a bolus of normal saline and a transfusion of two units of packed RBCs. CT scans of the chest, abdomen, and pelvis showed no adenopathy or splenomegaly. Although initial clinical assessment pointed toward a potential hematologic malignancy, comprehensive testing, including SPEP, reticulocyte count/fraction, serum folate, and serum vitamin B12, revealed only severe vitamin B12 deficiency, with a level of less than 150, with the presence of IF antibodies. Treatment involved intensive in-patient vitamin B12 injections followed by a detailed outpatient regimen. The patient completed a daily dose of vitamin B12 injections for seven consecutive days, followed by weekly injections for the next four weeks. Subsequent laboratory results demonstrated an increase in WBC count to 8.39, Hgb level to 13.2, and PLT count of 249, indicating a continued positive response to the vitamin B12 replacement therapy. In summary, pancytopenia poses a diagnostic challenge that demands careful evaluation of patient data and comprehensive testing. Vitamin B12 deficiency, which encompasses pernicious anemia (PA), is among the reversible factors to consider. This aspect holds significance before opting for more invasive measures like a bone marrow biopsy. Nutritional deficiencies need to be considered first as differentials in pancytopenia, even in the absence of typical signs of vitamin B12 deficiency (like macrocytosis and hypersegmented neutrophils) and in the presence of compelling clinical indications pointing to a hematologic malignancy.

Vitamin B12 deficiency poses significant health risks, especially among populations with limited access to animal-based foods. This study explores the utilisation of cereal bran by-products, wheat (WB) and oat bran (OB), as substrates for in situ vitamin B12 fortification through solid-state fermentation (SSF) using Propionibacterium freudenreichii. The impact of various precursors addition, including riboflavin, cobalt, nicotinamide and DMBI on vitamin B12 production, along with changes in microbial growth, chemical profiles, and vitamin B12 yields during fermentation was evaluated. Results showed that WB and OB possess favourable constituents for microbial growth and vitamin B12 synthesis. The substrates supplemented with riboflavin, cobalt, and DMBI demonstrated enhanced B12 production. In addition, pH levels are essential in microbial viability and cobalamin biosynthesis. Monosaccharides and organic acids play a crucial role, with maltose showing a strong positive association with B12 production in OB, while in WB, citric acid exhibits significant correlations with various factors.

The Burkholderia cepacia complex (Bcc) consists of opportunistic pathogens known to cause pneumonia in immunocompromised individuals, especially those with cystic fibrosis. Treating Bcc pneumonia is challenging due to the pathogens\' high multidrug resistance. Therefore, inhalation therapy with tobramycin powder, which can achieve high antibiotic concentrations in the lungs, is a promising treatment option. In this study, we investigated potential mechanisms that could compromise the effectiveness of tobramycin therapy. By selecting for Burkholderia cenocepacia survivors against tobramycin, we identified three spontaneous mutations that disrupt a gene encoding a key enzyme in the biosynthesis of cobalamin (Vitamin B12). This disruption may affect the production of succinyl-CoA by methylmalonyl-CoA mutase, which requires adenosylcobalamin as a cofactor. The depletion of cellular succinyl-CoA may impact the tricarboxylic acid (TCA) cycle, which becomes metabolically overloaded upon exposure to tobramycin. Consequently, the mutants exhibited significantly reduced reactive oxygen species (ROS) production. Both the wild-type and mutants showed tolerance to tobramycin and various other bactericidal antibiotics under microaerobic conditions. This suggests that compromised ROS-mediated killing, due to the impacted TCA cycle, underlies the mutants\' tolerance to bactericidal antibiotics. The importance of ROS-mediated killing and the potential emergence of mutants that evade it through the depletion of cobalamin (Vitamin B12) provide valuable insights for developing strategies to enhance antibiotic treatments of Bcc pneumonia.

BACKGROUND: Vitamin B12 deficiency is primarily associated with pernicious anaemia, polyneuropathy, and spinal-cord disease, but publications on its association with hallucinations are on the rise.
METHODS: I carried out a systematic literature search on these hallucinations in PubMed, PsycINFO, and Google Scholar, up until July 1, 2023.
RESULTS: The search yielded 50 case studies published between 1960 and 2023. The hallucinations described therein are predominantly visual and/or auditory in nature, with 20% being specified as complex, compound, or panoramic. They are often described in the context of vitamin B12-related neuropsychiatric conditions such as dementia, delirium, epilepsy, psychotic disorder, schizoaffective disorder, bipolar disorder, depressive disorder, catatonia, or obsessive-compulsive disorder. In the context of such disorders, they tend to appear first and also often appear to be the first to disappear with cobalamin treatment. Within an average of 2 months, full amelioration was thus obtained in 75% of the cases and partial amelioration in the remaining 25%. Remarkably, a quarter of the cases involved therapy-resistant hallucinations that fully resolved under cobalamin monotherapy, while other neuropsychiatric manifestations of vitamin B12 deficiency disappeared in 60% of the treated cases. Only 32% of the cases involved comorbid pernicious anaemia. This suggests that two separate or diverging pathways exist for perceptual and haematological symptoms of vitamin B12 deficiency.
CONCLUSIONS: In the light of the high prevalence rate of vitamin B12 deficiency in the general population, the findings here presented should be interpreted with great caution. Nonetheless, they offer cues for further research and experimental application in clinical practice. This may be especially relevant in light of the recent increase in the popularity of vegetarianism and the recreational use of nitrous oxide (laughing gas), which are both risk factors for vitamin B12 deficiency.

Although the green alga Chlamydomonas reinhardtii has long served as a reference organism, few studies have interrogated its role as a primary producer in microbial interactions. Here, we quantitatively investigated C. reinhardtii\'s capacity to support a heterotrophic microbe using the established coculture system with Mesorhizobium japonicum, a vitamin B12-producing α-proteobacterium. Using stable isotope probing and nanoscale secondary ion mass spectrometry (nanoSIMS), we tracked the flow of photosynthetic fixed carbon and consequent bacterial biomass synthesis under continuous and diurnal light with single-cell resolution. We found that more 13C fixed by the alga was taken up by bacterial cells under continuous light, invalidating the hypothesis that the alga\'s fermentative degradation of starch reserves during the night would boost M. japonicum heterotrophy. 15NH4 assimilation rates and changes in cell size revealed that M. japonicum cells reduced new biomass synthesis in coculture with the alga but continued to divide-a hallmark of nutrient limitation often referred to as reductive division. Despite this sign of starvation, the bacterium still synthesized vitamin B12 and supported the growth of a B12-dependent C. reinhardtii mutant. Finally, we showed that bacterial proliferation could be supported solely by the algal lysis that occurred in coculture, highlighting the role of necromass in carbon cycling. Collectively, these results reveal the scarcity of fixed carbon in this microbial trophic relationship (particularly under environmentally relevant light regimes), demonstrate B12 exchange even during bacterial starvation, and underscore the importance of quantitative approaches for assessing metabolic coupling in algal-bacterial interactions.

The causes and risk factors of vitamin B12 deficiency are many and varied. Importantly, they vary considerably across the lifespan, from infancy to old age. The complexity of the physiology of vitamin B12 bespeaks the myriad of possible causes of deficiency and possible disruptions of its functional integrity. These lead ultimately to the pathobiological effects witnessed in deficiency of this fascinating micronutrient. This brief overview of the multiplicity of mechanisms that can result in vitamin B12 deficiency, and the panoply of its manifestations explores the underlying reasons for the protean presentations of the disease. As the human organism progresses through the chronology and milestones of age, various susceptibility factors arise resulting from the interplay of environmental and genetic factors. Acting independently and in concert, these factors produce the common denominator of vitamin B12 deficiency. However, the rate at which such deficiency develops and the way in which it presents clinically vary widely, subject to such influences as genetic variability, end-organ susceptibility, and concomitant micronutrient status. Some examples of unusual cases of vitamin B12 deficiency are described. Much has been learned about the last of the numbered vitamins in almost a century. Much yet remains to be discovered.

UNASSIGNED: Little attention has been given to prenatal cobalamin insufficiency in settings where dietary cobalamin intake is presumed adequate, such as populations with habitual intake of foods from animal sources.
UNASSIGNED: However, low cobalamin status in women of fertile age has been reported in Europe, United States, and Canada. In India, where cobalamin deficiency is highly prevalent, it has been associated with an increased risk of miscarriage, intrauterine growth retardation, as well as insulin resistance and lower neurodevelopment scores in the offspring. Low cobalamin status in pregnancy has been associated with similar outcomes as those reported in the Indian studies although the evidence is scant and conflicting.
UNASSIGNED: Consideration should be given to maternal cobalamin status in the context of prevention of adverse pregnancy outcomes as well as cobalamin insufficiency both in the mother and the offspring during lactation. Further attention is now justified with the increasing tendency toward plant-based diets. Reference intervals for cobalamin status during each trimester of pregnancy are needed and further investigation of the long-term conse-quences of low cobalamin status during pregnancy for health and development in the offspring is warranted.
Plain language titleInadequate cobalamin status during critical periods of growth and development can have negative consequences on maternal and childhood health.

UNASSIGNED: An optimal cobalamin status is necessary for normal neurodevelopment.
UNASSIGNED: To give a description of the epidemiology, pathophysiology and diagnostic challenges related to cobalamin insufficiency in neonates and infants in order to prevent its occurence.
UNASSIGNED: Inadequate cobalamin status is prevalent among neonates and young infants, due to a high prevalence of maternal cobalamin deficiency, exclusive breastfeeding for extended periods and late introduction of animal food. Cobalamin insufficiency is associated with delayed neurodevelopment and subtle clinical symptoms like feeding difficulties, regurgitations and constipation in young infants. Early diagnosis and treatment of impaired cobalamin status is important to prevent neurologic damage.
UNASSIGNED: Clinical suspicion of cobalamin insufficiency in infants should infer immediate biochemical testing and a plasma total homocysteine > 5.0 µmol/L indicate cobalamin insufficiency in need of intramuscular treatment with hydroxycobalamin, followed by introduction of animal food after 4 months of age.
Plain language titleVitamin B12 Is Important for Normal Development in Young ChildrenPlain language summaryVitamin B12, also called cobalamin, is found only in animal-sourced food. As low-meat, vegetarian, and vegan diets are increasingly popular in Western countries, vitamin B12 deficiency has become common, also in pregnant women and babies. Vitamin B12 status is essential for normal development and adequate levels of this vitamin is particularly important during pregnancy and the first years of life. In pregnancy, vitamin B12 is transferred from the mother to the fetus, so the baby has a store of this vitamin at birth. However, if the mother has vitamin B12 deficiency or the baby is born premature or with a low birth weight, the vitamin store may be insufficient and the baby may develop vitamin B12 deficiency. Maternal vitamin B12 status is important as long as the baby is exclusively breastfed. Breast milk contains vitamin B12, but the concentration decreases after 4 to 6 weeks and may be too low to support the baby until animal-sourced foods are introduced. The vitamin B12 content in formula milk is higher than in breast milk, and vitamin B12 deficiency is more common in exclusively breastfed babies. Vitamin B12 deficiency is associated with diffuse symptoms in small babies and may be difficult to detect, and the diagnosis have a mean delay of 4 months in this age-group. Typical symptoms are regurgitations or spitting up, constipation, problems with feeding and swallowing, and delayed psychomotor development. Suspicion of vitamin B12 insufficiency in babies should prompt immediate biochemical testing. Plasma total homocysteine is a metabolic marker of vitamin B12 status and can be measured in a blood sample from the baby. A level >5.0 µmol/L indicates probable vitamin B12 insufficiency and the baby should receive vitamin B12 supplementation, followed by introduction of animal-sourced foods at 3 to 4 months of age.

OBJECTIVE: Nutrition plays a crucial role in the development and health of the human brain, from early stages to adulthood. The complex process of neurodevelopment necessitates interaction among various factors, with balance in the concentration of vital macronutrients and micronutrients being essential. Regarding micronutrients, vitamin B12 stands out, playing a vital role in the development and functioning of the motor nervous system. The objective was to investigate the influence of reduced levels of vitamin B12 on infant motor development and analyze the effects of supplementation on this aspect of development.
METHODS: For this purpose, the criteria of the PRISMA method and registration in the PROSPERO database were used. The search was conducted in the following databases: PubMed (Medline), Scopus, PsycINFO, Web of Science, and ScienceDirect. A total of 684 records were initially identified.
RESULTS: Of the eight included articles, there was diversity regarding geographical contexts and study designs. The final sample comprised a total of 1,559 participants of both sexes. Studies aimed at correcting low levels of vitamin B12 opted for supplementation, following various protocols that varied in dose, administration method, and duration. At the end of the studies, the serum level of this vitamin ranged from 131 pmol/L to 1141 pmol/L.
CONCLUSIONS: There is a complex array of factors contributing to reduced levels of vitamin B12, especially in the early stages of life, which significantly impacts infant motor development. Despite methodological variations among studies, evidence suggests that low levels of vitamin B12 may affect motor development and that supplementation could be an effective means of enhancing motor aspects in healthy children. However, due to the diversity of outcomes, it is important to promote comprehensive public policies to encourage appropriate interventions in this area.

Currently, obesity is a critical global public health burden. Numerous studies have demonstrated the regulation of the pathogenesis of obesity and metabolic abnormalities by the gut microbiota and microbial factors; however, their involvement in the various degrees of obesity is not yet well understood. Previously, obesity has been shown to be associated with decreased levels of vitamin B12. Considering exclusive microbial production of vitamin B12, we hypothesized that a decrease in cobalamin levels in obese individuals may be at least partially caused by its depleted production in the intestinal tract by the commensal microbiota. In the present study, our aim was to estimate the abundance of enzymes and metabolic pathways for vitamin B12 synthesis in the gut microbiota of mouse models of alimentary and genetically determined obesity, to evaluate the contribution of the obesogenic microbiome to vitamin B12 synthesis in the gut. We have defined a significantly lower predicted abundance of enzymes and metabolic pathways for vitamin B12 biosynthesis in obese mice compared to non-obese mice, wherein enzyme depletion was more pronounced in lepr(-/-) (db/db) mice, which developed severe obesity. The predicted abundance of enzymes involved in cobalamin synthesis is strongly correlated with the representation of several microbes in high-fat diet-fed mice, while there were almost no correlations in db/db mice. Therefore, the degree of obesity and the composition of the correspondent microbiota are the main contributors to the representation of genes and pathways for cobalamin biosynthesis in the mouse gut.