Interest toward the human microbiome, particularly gut microbiome has flourished in recent decades owing to the rapidly advancing sequence-based screening and humanized gnotobiotic model in interrogating the dynamic operations of commensal microbiota. Although this field is still at a very preliminary stage, whereby the functional properties of the complex gut microbiome remain less understood, several promising findings have been documented and exhibit great potential toward revolutionizing disease etiology and medical treatments. In this review, the interactions between gut microbiota and the host have been focused on, to provide an overview of the role of gut microbiota and their unique metabolites in conferring host protection against invading pathogen, regulation of diverse host physiological functions including metabolism, development and homeostasis of immunity and the nervous system. We elaborate on how gut microbial imbalance (dysbiosis) may lead to dysfunction of host machineries, thereby contributing to pathogenesis and/or progression toward a broad spectrum of diseases. Some of the most notable diseases namely Clostridium difficile infection (infectious disease), inflammatory bowel disease (intestinal immune-mediated disease), celiac disease (multisystemic autoimmune disorder), obesity (metabolic disease), colorectal cancer, and autism spectrum disorder (neuropsychiatric disorder) have been discussed and delineated along with recent findings. Novel therapies derived from microbiome studies such as fecal microbiota transplantation, probiotic and prebiotics to target associated diseases have been reviewed to introduce the idea of how certain disease symptoms can be ameliorated through dysbiosis correction, thus revealing a new scientific approach toward disease treatment. Toward the end of this review, several research gaps and limitations have been described along with suggested future studies to overcome the current research lacunae. Despite the ongoing debate on whether gut microbiome plays a role in the above-mentioned diseases, we have in this review, gathered evidence showing a potentially far more complex link beyond the unidirectional cause-and-effect relationship between them.

/pdf/the-human-gut-microbiome-a-potential-controller-of-wellness-4iblq6fqqr.pdf

The human gut microbiome - A potential controller of wellness and disease

Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification.

VITAMIN B12 OR COBALAMIN DEFICIENCY occurs frequently (> 20%) among elderly people, but it is often unrecognized because the clinical manifestations are subtle; they are also potentially serious, particularly from a neuropsychiatric and hematological perspective. Causes of the deficiency include, most frequently, food-cobalamin malabsorption syndrome (> 60% of all cases), pernicious anemia (15%–20% of all cases), insufficent dietary intake and malabsorption. Food-cobalamin malabsorption, which has only recently been identified as a significant cause of cobalamin deficiency among elderly people, is characterized by the inability to release cobalamin from food or a deficiency of intestinal cobalamin transport proteins or both. We review the epidemiology and causes of cobalamin deficiency in elderly people, with an emphasis on food-cobalamin malabsorption syndrome. We also review diagnostic and management strategies for cobalamin deficiency.

/pdf/vitamin-b12-cobalamin-deficiency-in-elderly-patients-4am8cz9m0v.pdf

Vitamin B12 (cobalamin) deficiency in elderly patients

The human gut microbiota supplies its host with essential nutrients, including B-vitamins. Using the PubSEED platform, we systematically assessed the genomes of 256 common human gut bacteria for the presence of biosynthesis pathways for eight B-vitamins: biotin, cobalamin, folate, niacin, pantothenate, pyridoxine, riboflavin, and thiamin. On the basis of the presence and absence of genome annotations, we predicted that each of the eight vitamins was produced by 40-65% of the 256 human gut microbes. The distribution of synthesis pathways was diverse; some genomes had all eight biosynthesis pathways, whereas others contained no de novo synthesis pathways. We compared our predictions to experimental data from 16 organisms and found 88% of our predictions to be in agreement with published data. In addition, we identified several pairs of organisms whose vitamin synthesis pathway pattern complemented those of other organisms. This analysis suggests that human gut bacteria actively exchange B-vitamins among each other, thereby enabling the survival of organisms that do not synthesize any of these essential cofactors. This result indicates the co-evolution of the gut microbes in the human gut environment. Our work presents the first comprehensive assessment of the B-vitamin synthesis capabilities of the human gut microbiota. We propose that in addition to diet, the gut microbiota is an important source of B-vitamins, and that changes in the gut microbiota composition can severely affect our dietary B-vitamin requirements.

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Systematic genome assessment of B-vitamin biosynthesis suggests co-operation among gut microbes.

http://www.med.monash.edu.au/assets/docs/scs/psychiatry/psychopharmacology/turnheim_meds_elderly_2011.pdf

When drug therapy gets old: pharmacokinetics and pharmacodynamics in the elderly.

Summary

Background: It has been suggested that oral cobalamin (vitamin B12) therapy may be an effective therapy for treating cobalamin deficiencies related to food-cobalamin malabsorption. However, the duration of this treatment was not determined.



Patients and method: In an open-label, nonplacebo study, we studied 30 patients with established cobalamin deficiency related to food-cobalamin malabsorption, who received between 250 and 1000 μg of oral crystalline cyanocobalamin per day for at least 1 month.



Endpoints: Blood counts, serum cobalamin and homocysteine levels were determined at baseline and during the first month of treatment.



Results: During the first month of treatment, 87% of the patients normalized their serum cobalamin levels; 100% increased their serum cobalamin levels (mean increase, +167 pg/dl; P < 0.001 compared with baseline); 100% had evidence of medullary regeneration; 100% corrected their initial macrocytosis; and 54% corrected their anemia. All patients had increased hemoglobin levels (mean increase, +0.6 g/dl) and reticulocyte counts (mean increase, +35 × 106/l) and decreased erythrocyte cell volume (mean decrease, 3 fl; all P < 0.05).



Conclusion: Our findings suggest that crystalline cyanocobalamin, 250–1000 μg /day, given orally for 1 month, may be an effective treatment for cobalamin deficiencies not related to pernicious anemia.

Efficacy of short-term oral cobalamin therapy for the treatment of cobalamin deficiencies related to food-cobalamin malabsorption: a study of 30 patients.

OBJECTIVES The aim of this trial was to demonstrate the efficacy of one month of oral cobalamin (vitamin B12) therapy in elderly patients with cobalamin deficiency related to food-cobalamin malabsorption (FCM). PATIENTS AND METHOD Twenty elderly patients (mean age: 78+/-17 years) with established cobalamin deficiency related to FCM were included in an open-label, non-randomized, non-placebo trial. They were treated with a maximum of 1,000 microgram per day of oral crystalline cyanocobalamin for at least 1 month. Serum cobalamin levels (primary endpoint), blood count abnormalities and reticulocytes count (secondary endpoints) were determined at baseline and during the first month of treatment. RESULTS 85% of the patients normalized their serum cobalamin levels with a mean increase of+167 pg/ml (p<0.001 compared with baseline). 100% of the patients corrected their initial macrocytosis and 25% their anemia; 100% of the patients had medullar regeneration with a mean increase of reticulocytes count of 32+/-11.3 x 106/l (p=0.03 compared with baseline). CONCLUSIONS Our findings support the view that one month of oral crystalline cyanocobalamin is effective to correct serum vitamin B12 levels and to obtain hematological responses in elderly patients with cobalamin deficiency related to FCM.

Hematological response to short-term oral cyanocobalamin therapy for the treatment of cobalamin deficiencies in elderly patients.

Propos : Le traitement classique des hypovitaminoses B12 repose sur l'administration intra-musculaire de cobalamine. Le but de cette etude est de montrer que les hypovitaminoses B12 par carence d'apport et surtout par non dissociation de la vitamine B12 de ses proteines porteuses peuvent etre rapidement corrigees par un traitement oral chez les personnes âgees. Patients et methodes : Il s'agit d'une etude prospective incluant 20 personnes âgees de plus de 80 ans ayant une hypovitaminose B12 par non dissociation de la vitamine B12 (n = 14) et par carence d'apport (n = 6). Tous les patients ont ete traites par 1 000 μg de cyanocobalamine administree quotidiennement par voie orale. Les dosages de la vitaminemie B12 et des parametres hematologiques ont ete effectues avant traitement, puis une semaine plus tard. Resultats: Apres 8 jours de traitement en moyenne, les valeurs de la vitaminemie B12 se sont normalisees chez 17 patients sur 20; la vitamine B12 serique a augmente en moyenne de 0,23 μg/L (p < 0,01), les reticulocytes de 27 400/mm 3 (p < 0,05), le taux d'hemoglobine de 0,7 g/dL (NS) et le volume globulaire moyen a diminue de 0,7 fL (NS). Conclusion: Cette etude prospective montre que les hypovitaminoses B12 par carence d'apport et surtout par non dissociation de la vitamine B12 peuvent etre rapidement corrigees en une semaine par de la cyanocobalamine administree par voie orale. Des injections intra-musculaires repetees et douloureuses peuvent ainsi etre evitees chez les personnes âgees.

Early response to oral cobalamin therapy in older patients with vitamin B12 deficiency

https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1532-5415.2002.50533.x

M. Noblet-Dick

Papers

Vitamin B12 (cobalamin) deficiency in elderly patients

Efficacy of short-term oral cobalamin therapy for the treatment of cobalamin deficiencies related to food-cobalamin malabsorption: a study of 30 patients.

Hematological response to short-term oral cyanocobalamin therapy for the treatment of cobalamin deficiencies in elderly patients.

Early response to oral cobalamin therapy in older patients with vitamin B12 deficiency

Early Normalization of Low Vitamin B12 Levels by Oral Cobalamin Therapy in Three Older Patients With Pernicious Anemia