Nutrition, Inflammation, and the Gut Microbiota among Outpatients with Active Tuberculosis Disease in India.

India has the highest rates of tuberculosis (TB) globally and a high prevalence of malnutrition; however, the interplay between host nutritional status, inflammation, and the gut microbiome in active tuberculosis disease (ATBD) is less well-studied. We examined differences in gut microbial composition and diversity based on undernutrition and inflammation status among outpatients with ATBD at the time of treatment initiation. During this exploratory cross-sectional study, outpatients (N = 32) with ATBD (confirmed by Xpert MTB/RIF) were enrolled in anti-TB treatment initiated at a hospital in rural southern India. The 16S rRNA sequencing was used to assess the composition of the gut microbiome. We assessed multiple markers of nutritional status, including micronutrient status concentrations (vitamin D [25(OH)D], vitamin B12, ferritin), anthropometry (body mass index, mid-upper arm circumference, and height), and C-reactive protein (CRP), as indicators of inflammation. We found that 25(OH)D was positively associated with the relative abundance of Oscillospira spp., a butyrate-producing genus linked with anti-inflammation effects, and that ferritin was positively associated with Proteobacteria taxa, which have been associated with worse inflammation in other studies. Finally, we found a greater abundance of inflammation-associated taxa from the Proteobacteria phylum and lower alpha-diversity indices among those who were underweight or who had low mid-upper arm circumference or short stature. In summary, we found differences in the gut microbiota composition and diversity among those with undernutrition compared with those with adequate nutrition status at the time of initiation of treatment among patients with ATBD in India. Clinical implications of these findings will need to be examined by larger longitudinal studies.

The impact of vitamin B12 deficiency on infant gut microbiota.

Although physiologic and neurologic consequences of micronutrient deficiencies have been addressed extensively, less is known about their impact on developing gut microbiota. Vitamin B12 deficiency is a common micronutrient deficiency in infants. We aimed to analyze the gut microbial composition of exclusively breastfed infants aged between 4 and 6 months with and without vitamin B12 deficiency by 16S rRNA gene sequencing. In a subgroup of infants with vitamin B12 deficiency, stool samples are recollected and reanalyzed after vitamin B12 supplementation. A total of 88 infants' stool samples (median age 4 months [IQR 4-5], 50% males) were analyzed, of which 28 (31.8%) were vitamin B12 sufficient and 60 (68.2%) were vitamin B12 insufficient. Comparisons between vitamin B12-sufficient and vitamin B12-insufficient infants revealed no evidence of differences in the microbiota. Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes were the most abundant phyla in all groups. There was no difference between the pre- and post-treatment composition of gut microbiota.Conclusion: Vitamin B12-deficient infants have similar gut microbial composition as vitamin B12-sufficient infants. Since the samples were collected at an early period of life and the exposure to deficiency was relatively short, it may be possible that the effects were not fully established.What is Known: • Vitamin B12 is an essential vitamin for humans and also a crucial compound for human gut microbiota. • Vitamin B12 deficiency is common in exclusively breastfed infants. • In contrast to the adult gut microbiota, infant gut microbiota has been shown to have decreased capacity for de novo synthesis of vitamin B12 and depend on dietary source of vitamin B12.What is New: • There is no difference in the gut microbial composition of vitamin B12-deficient and vitamin B12-sufficient infants.

The Relation of Cytotoxin-Associated Gene-A Seropositivity with Vitamin B12 Deficiency in Helicobacter pylori-Positive Patients.

BACKGROUND AND AIM: As a worldwide infectious bacterium, H. pylori leads to stomach pathologies such as gastritis, peptic ulcer, gastric cancer, MALToma, and various extragastric manifestations. In our study, we aimed to investigate the association between serum vitamin B12 level and cytotoxin-associated gene-A (CagA) seropositivity, which is one of the virulence factors of Helicobacter pylori (H. pylori). METHOD: This study has been conducted on 289 patients who have met the inclusion criteria. Within these patients, 213 of them were H. pylori positive and 76 were negative. Vitamin B12 and CagA-IgG levels were assessed in consecutive dyspeptic patients undergoing upper endoscopy. RESULTS: Out of 289 patients, 51.9% were women (n = 150) and H. pylori was detected in 213 (73.7%) patients. Histopathological evaluation with modified Sydney classification revealed lymphocyte infiltration in 66.8% (n = 193), activation in 46% (n = 133), metaplasia in 11.4% (n = 33), atrophy in 11.4% (n = 33), and lymphoid follicles in 21.1% (n = 61) of the patients. Within H. pylori-positive patients, the ratio of CagA positivity was 57.3% (n = 122). Low B12 vitamin level was significantly correlated with existence of H. pylori (p=0.02), CagA (p=0.002), lymphocyte (p=0.006), metaplasia (p=0.001), atrophy (p=0.001), and lymphoid follicles (p=0.006). Positivity of CagA has been detected to be statistically corelated with lymphocyte (p=0.001) and activation (p=0.005); however, the same relation was not present with atrophy (p=0.236). CONCLUSION: In conclusion, B12 deficiency was positively correlated with CagA positivity and gastric inflammatory activity.

Helicobacter pylori and hematological disorders.

Helicobacter pylori (H. pylori) is one of the most common worldwide infections, which can affect both adults and children. The prevalence of this bacterium is variable in different countries, depending on various hygienic and socioeconomic conditions and living customs. The major damaged tissues of the infection are in the upper gastrointestinal tract, causing gastritis, gastric and duodenal ulcer and gastrointestinal malignancy. Nevertheless, other disorders are associated with this pathogen, including several hematological diseases, such as iron deficiency anemia, immune thrombocytopenia and vitamin B12 deficiency. A huge of data in literature support these associations, enough to recognize them in the last Maastricht V/Florence Consensus Report by European Study Group. The pathogenic mechanisms underlying the linkage between H. pylori and these hematological disorders are not clearly identified, but certainly the good hematological response reaches after eradication therapy confirm a central role of the bacterium in this scenario. Instead, the pathogenic mechanisms of H. pylori infection, which lead to the occurrence of mucosa-associated lymphoid tissue (MALT) lymphoma are clearer and more consolidated; so much that nowadays eradication therapy alone represents the only treatment in this disorder, when localized and with a concomitant H. pylori infection. This review focuses on the hematologic diseases related to H. pylori, particularly on iron deficiency anemia, vitamin B12 deficiency, immune thrombocytopenia and gastric MALT lymphoma.

Interplay between mitochondria and diet mediates pathogen and stress resistance in Caenorhabditis elegans.

Diet is a crucial determinant of organismal biology; interactions between the host, its diet, and its microbiota are critical to determining the health of an organism. A variety of genetic and biochemical means were used to assay stress sensitivity in C. elegans reared on two standard laboratory diets: E. coli OP50, the most commonly used food for C. elegans, or E. coli HT115, which is typically used for RNAi-mediated gene knockdown. We demonstrated that the relatively subtle shift to a diet of E. coli HT115 had a dramatic impact on C. elegans's survival after exposure to pathogenic or abiotic stresses. Interestingly, this was independent of canonical host defense pathways. Instead the change arises from improvements in mitochondrial health, likely due to alleviation of a vitamin B12 deficiency exhibited by worms reared on an E. coli OP50 diet. Increasing B12 availability, by feeding on E. coli HT115, supplementing E. coli OP50 with exogenous vitamin B12, or overexpression of the B12 transporter, improved mitochondrial homeostasis and increased resistance. Loss of the methylmalonyl-CoA mutase gene mmcm-1/MUT, which requires vitamin B12 as a cofactor, abolished these improvements, establishing a genetic basis for the E. coli OP50-incurred sensitivity. Our study forges a mechanistic link between a dietary deficiency (nutrition/microbiota) and a physiological consequence (host sensitivity), using the host-microbiota-diet framework.

Helicobacter pylori and extragastric diseases.

Many studies have been performed in the last year concerning the potential role of Helicobacter pylori in different extragastric diseases, reinforcing the idea that specific microorganisms may cause diseases even far from the primary site of infection. While the role of H. pylori on idiopathic thrombocytopenic purpura, sideropenic anemia, and vitamin B12 deficiency has been well established, there is a growing interest in other conditions, such as cardiovascular, neurologic, dermatologic, obstetric, immunologic, and metabolic diseases. Concerning neurologic diseases, there is a great interest in cognitive impairment and neurodegeneration. The aim of this review was to summarize the results of the most relevant studies published over the last year on this fascinating topic.

Hepatic fungal infection in a young beagle with unrecognised hereditary cobalamin deficiency (Imerslund-Gräsbeck syndrome).

A 12-month-old beagle presented for anorexia, pyrexia and vomiting. The dog had been treated intermittently with antibiotics and corticosteroids for inappetence and lethargy since five months of age. Previous laboratory abnormalities included macrocytosis and neutropenia. At presentation, the dog was lethargic, febrile and thin. Laboratory examination findings included anaemia, a left shift, thrombocytopenia, hypoglycaemia and hyperbilirubinaemia. Multiple, small, hypoechoic, round hepatic lesions were observed on abdominal ultrasound. Cytological examination of hepatic fine needle aspirates revealed a fungal infection and associated pyogranulomatous inflammation. The dog's general condition deteriorated despite supportive measures and treatment with fluconazole, and owners opted for euthanasia before hypocobalaminaemia was identified. Subsequent genomic analysis revealed a CUBN:c.786delC mutation in a homozygous state, confirming hereditary cobalamin malabsorption (Imerslund-Gräsbeck syndrome). Similar to human infants, dogs with Imerslund-Gräsbeck syndrome may rarely be presented for infectious diseases, distracting focus from the underlying primary disorder.

Helicobacter pylori and extragastric diseases.

While Helicobacter pylori infection was initially revealed to be associated only with some gastroduodenal diseases, further studies have shown its possible role in several extragastric diseases. For idiopathic thrombocytopenic purpura, sideropenic anemia, and vitamin B12 deficiency, the diagnosis of H. pylori infection is recommended, and there are many other conditions such as cardiovascular, neurological, dermatological, and respiratory diseases in which H. pylori may possibly play a role. Interestingly, a potential role has also been described for GI neoplastic diseases, including colorectal and pancreatic cancer. Different mechanisms of action have been proposed, ranging from the induction of a low grade inflammatory state to the occurrence of molecular mimicry mechanisms. This review summarizes the results of the most relevant studies published on this topic over the last year.

Ultrastructure of the H. pylori microbe in individuals having macrocytosis and B12 deficiency.

The incidence of Helicobacter pylori gastritis is high in India and the number of individuals with vitamin B12 deficiency is also large. An association has been found between these two factors. It is necessary to determine whether H. pylori infection may be a factor in the causation of B12 deficiency and whether it is associated with any morphological changes on ultrastructural examination. A cohort-based study has been performed, which includes 505 young asymptomatic males. These cases have been investigated for presence of H. pylori and macrocytosis. The study confirms an association between H. pylori infection and B12 deficiency. It is recommended that H. pylori infection be looked for in subjects having macrocytosis of unknown etiology.

[Helicobacter pylori and Arteriosclerosis].

Helicobacter pylori (H. pylori) infection-related diseases are known to include gastritis, gastric and duodenal ulcer, gastric cancer, gastric MALT lymphoma, idiopathic thrombocytopenic purpura, iron-deficient anemia, urticaria, reflux esophagitis, and some lifestyle-related diseases. It is indicated that homocysteine involved with arteriosclerosis induces lifestyle-related diseases. Homocysteine is decomposed to methionine and cysteine (useful substances) in the liver, through the involvement of vitamin B12 (VB12) and folic acid. However, deficiency of VB12 and folic acid induces an increase in unmetabolized homocysteine stimulating active oxygen and promoting arteriosclerosis. VB12 and folic acid are activated by the intrinsic factors of gastric parietal cells and gastric acid. The question of whether homocysteine, as a trigger of arteriosclerosis, was influenced by H. pylori infection was investigated. H. pylori infection induces atrophy of the gastric mucosa, and the function of parietal cells decreases with the atrophy to inactivate its intrinsic factor. The inactivation of the intrinsic factor causes a deficiency of VB12 and folic acid to increase homocysteine's chances of triggering arteriosclerosis. The significance and usefulness of H. pylori eradication therapy was evaluated for its ability to prevent arteriosclerosis that induces lifestyle-related diseases. Persons with positive and negative results of H. pylori infection were divided into a group of those aged 65 years or more (early and late elderly) and a group of those under 65 years of age, and assessed for gastric juice. For twenty-five persons from each group who underwent gastrointestinal endoscopy, the degree of atrophy of the gastric mucosa was observed. Blood homocysteine was measured as a novel index of arteriosclerosis, as well as VB12 and folic acid that affect the metabolism of homocysteine, and then activated by gastric acid and intrinsic factors. Their arterioscleroses, measured by pulse wave velocity (PWV), were investigated and compared. The levels of homocysteine were significantly high in the elderly persons and those with H. pylori infection. On the contrary, the levels of VB12 and folic acid were low in these persons. The results of PWV showed a positive correlation with the levels of gastrin and homocysteine and an inverse correlation with the levels of VB12 and folic acid. Persons with a negative result of H. pylori infection showed a lower degree of arteriosclerosis than those with a positive result who were of the same age group. Persons with a positive result of H. pylori infection tended to show an improvement from arteriosclerosis after eradication therapy without a significant difference. 1 ) It is suggested that severity of atrophy of the gastric mucosa are correlated with the severity of arteriosclerosis. 2 ) It is hypothesized that H. pylori infection may induce arteriosclerosis.

Association of autoimmune type atrophic corpus gastritis with Helicobacter pylori infection.

AIM: To study the association between Helicobacter pylori (H. pylori) infection and autoimmune type atrophic gastritis. METHODS: Twenty-three patients with different grades of atrophic gastritis were analysed using enzyme immunoassay-based serology, immunoblot-based serology, and histology to reveal a past or a present H. pylori infection. In addition, serum markers for gastric atrophy (pepsinogen I, pepsinogen I/II and gastrin) and autoimmunity [parietal cell antibodies (PCA), and intrinsic factor (IF), antibodies] were determined. RESULTS: Of the 14 patients with severe gastric atrophy, as demonstrated by histology and serum markers, and no evidence for an ongoing H. pylori infection, eight showed H. pylori antibodies by immunoblotting. All eight had elevated PCA and 4/8 also had IF antibodies. Of the six immunoblot-negative patients with severe corpus atrophy, PCA and IF antibodies were detected in four. Among the patients with low to moderate grade atrophic gastritis (all except one with an ongoing H. pylori infection), serum markers for gastric atrophy and autoimmunity were seldom detected. However, one H. pylori negative patient with mild atrophic gastritis had PCA and IF antibodies suggestive of a pre-atrophic autoimmune gastritis. CONCLUSION: Signs of H. pylori infection in autoimmune gastritis, and positive autoimmune serum markers in H. pylori gastritis suggest an etiological role for H. pylori in autoimmune gastritis.

Long-term effect of Helicobacter pylori eradication on plasma homocysteine in elderly patients with cobalamin deficiency.

BACKGROUND: Helicobacter pylori gastritis may lead to impairment of the production of pepsinogen and acid, which are essential to cobalamin absorption. In turn, cobalamin deficiency leads to hyperhomocysteinaemia, a risk factor for cardio and cerebrovascular diseases. AIM: To evaluate the effect of H pylori eradication on plasma homocysteine levels in elderly patients. PATIENTS: Sixty-two H pylori-positive elderly patients with cobalamin deficiency were prospectively studied. METHODS: Homocysteine and cobalamin concentrations were determined before, 6 and 12 months after H pylori eradication. RESULTS: Corpus atrophy was observed in a few patients; otherwise, in most of them, the degree of corpus gastritis was moderate to severe. The initial homocysteine mean (SD) levels decreased from 41.0 (27.1) to 21.6 (10.1) micromol/l at the 6 month follow-up (p<0.001) and to 13.1 (3.8) micromol/l 12 months after H pylori eradication (p<0.001). Conversely, initial cobalamin mean levels increased from 145.5 (48.7) pmol/l to 209.8 (87.1) pmol/l and to 271.2 (140.8) pmol/l, 6 and 12 months after treatment, respectively (p<0.001 for both). Although the erythrocyte mean corpuscular volume was within reference intervals, it decreased significantly 6 (p = 0.002) and 12 (p<0.001) months after treatment. CONCLUSIONS: The results of the current study demonstrated that the eradication of H pylori in elderly patients with cobalamin deficiency is followed by increasing of cobalamin and decreasing of homocysteine blood levels.

[Macrocytic megaloblastic anaemia in a patient with Helicobacter pylori infection]. / Niedokrwistosc makrocytarna megaloblastyczna u chorego z zakazeniem Helicobacter pylori.

We present 62 yrs old patient in whom megaloblastic anaemia due to vitamin B12 depletion was caused by Helicobacter pylori infection. An eradication treatment with the vitamin B12 supplementation within 7 days resulted in withdrawal of the abnormalities in the blood smear. The inflammation of gastric mucosa with intestine metaplasia is still observed. According to the letters these changes may persist up to 2-3 years after treatment ending.

Metabolism of mycotoxins, intracellular functions of vitamin B12, and neurological manifestations in patients with chronic toxigenic mold exposures. A review.

This paper evaluates the possible reasons for consistent vitamin B12 deficiency in chronic toxigenic mold exposures and the synergistic relationships with the possible mycotoxic effects on one-carbon metabolism that lead to the manifestations of clinical neuropathological symptomology. Vitamins are first defined in general and the nutritional sources of vitamin B12 are evaluated in particular. Since patients with chronic exposures to toxigenic molds manifest vitamin B12 deficiencies, the role of mycotoxins in vitamin B12 metabolism is assessed, and since vitamin B12 plays important biochemical roles in one-carbon metabolism, the synergistic effects with mycotoxins on humans are reviewed. An outline of the proposed mechanism by which mycotoxins disrupt or interfere with the normal functions of vitamin B12 on one-carbon metabolism is proposed. The overall functions of vitamin B12 as a source of coenzymes, in intracellular recycling of methionine, in methionine synthase reaction, in the prevention of chromosome breakage, in methylation, and in maintaining a one-carbon metabolic balance are reviewed. Signs, symptoms, and clinical neurological indications of vitamin B12 deficiency are also cited. By implication and derivation, it is likely that the interruption of the structure and function of vitamin B12 would in turn interfere with the one-carbon metabolism leading to the neurological manifestations. This review is an attempt to formulate a basis for an ongoing research investigation on the subject.

[Helicobacter pylori can in rare cases be the cause of iron and vitamin B 12 deficiency. No increased risk of iron and vitamin B 12 deficiency due to proton pump inhibitors]. / Helicobacter pylori kan i sällsynta fall orsaka järn- och vitamin B12-brist. Ingen ökad risk för järn- eller B12-brist med protonpumpshämmare.

This article reviews iron and vitamin B12 malabsorption due to the use of proton pump inhibitors (PPI) and infection with Helicobacter pylori. The bacterium is in some studies associated with low serum values of both ferritin and cobalamin and has in several cases been shown to cause reversible deficiency of these nutrients. PPI depresses absorption of vitamin B12, but only one case of deficiency has been reported in standard reflux therapy. Case reports exist of PPI-related iron deficiency, but studies have not confirmed these risks. General substitution with iron or B12 supplements in PPI therapy can't be advocated. The safety of long-term use of PPI is well documented, but it is still unclear whether PPI accelerates the development of atrophic corpus gastritis in the presence of H pylori.

Vitamin B12 status and its association with Helicobacter pylori infection in alcohol dependent patients.

Both infection with Helicobacter pylori and alcohol abuse have been associated with low vitamin B12 serum levels. The interaction between both risk factors is unknown. The aim of this study was to determine whether Helicobacter pylori infection is associated with low vitamin B12 levels in alcohol dependent patients. Blood samples were obtained from adult alcohol dependent patients undergoing detoxification and analyzed for serum vitamin B12 levels. Helicobacter pylori infection was serologically measured. Patient characteristics, medication use and alcohol consumption at admission were assessed by interview. A total of 6 out of 89 patients included presented low vitamin B12 levels, all were sub clinical deficient (<250 pmol/L) and none were clinical deficient (<150 pmol/L). Infection with Helicobacter pylori was present in 29% of the patients. The average vitamin B12 levels in Helicobacter pylori seropositive and seronegative patients were 1,033 pmol/L (SD 741) and 971 pmol/L (SD 717), respectively. The relation between Helicobacter pylori infection and vitamin B12 deficiency was not of significance (OR=0.48; 95% CI [0.05-4.32]). In conclusion, Helicobacter pylori infection is not a risk factor for low vitamin B12 levels in alcohol dependent patients.

Helicobacter pylori infection, vitamin B12 and homocysteine. A review.

It has been suggested that there is an association between Helicobacter pylori infection, reduced cobalamin absorption and cobalamin status and, consequently, elevated homocysteine levels. This would offer an explanation why H. pylori infection is associated with coronary heart disease. To date, more than 25 studies have been published that either deal with H. pylori infection and homocysteine, H. pylori infection and cobalamin status, or both. The design of these studies differs widely in terms of definition of H. pylori status, measuring cobalamin status, selection of study cohorts and geographical study areas. Therefore, results are fairly inconclusive at present and do not suggest a major role of H. pylori infection in the development of cobalamin deficiency and elevated homocysteine levels.