Comparison of Oral and Esophageal Microbiota in Patients with Achalasia Before and After Peroral Endoscopic Myotomy.

BACKGROUND/AIMS: Patients with achalasia have a high incidence of esophageal squamous cell carcinoma (ESCC), which may be associated with alterations in oral and esophageal microbiota caused by food stasis. This study compared the oral and esophageal microbiota of patients with achalasia before and after peroral endoscopic myotomy (POEM). It also compared patients with achalasia to those with ESCC. MATERIALS AND METHODS: The study prospectively examined 6 patients with achalasia and 14 with superficial ESCC. Oral samples obtained from the buccal mucosa using a swab and esophageal samples obtained from the mid-esophagus using a brush via endoscopy were analyzed by 16S rRNA metagenome sequencing. Additionally, endoscopic and histological findings of patients with achalasia before and after POEM were prospectively compared. RESULTS: In patients with achalasia, Streptococcus was most abundant in both the oral and the esophageal microbiota, and these microbiota were significantly different. Although the overall structure of the oral and esophageal microbiota did not change after POEM, the relative abundance rate of Haemophilus and Neisseria increased in the esophagus, and endoscopic findings of inflammation improved after POEM (P = .04). The relative abundance of microbiota was not different among patients with achalasia from those with ESCC. CONCLUSIONS: The oral and esophageal microbiota were significantly different in patients with achalasia, and some of the composition of the esophageal microbiota changed after POEM. However, these findings and disease-specific microbiota should be further evaluated in large-scale studies.

Mycobacterium Fortuitum infection associated with achalasia.

The association between achalasia and no tuberculosis mycobacterial   lung infection is well described in the literature. MycobactériumFortuitum is often responsible, and the clinical's presentation   is an aspiration pneumonia resistant to usual antibiotic therapy. We report the case of a 15 year-old patient with the history of Allgrove syndrome. The chest imaging showed right lung congestion; the diagnosis was bacteriological and MycobactériumFortuitum resistant to rifampicin, isoniazid, pyrazinamide and ethambutol was isolated. The patient was treated by the association cotrimoxazole, ciprofloxacin and clarithromycin for 12 months and the clinical, radiological and bacteriological outcomes were favorable. To prevent the recurrence the patient benefited from a cardiomyotomy.

Larger amounts of nitrite and nitrate-reducing bacteria in megaesophagus of Chagas' disease than in controls.

In the megaesophagus of Chagas' disease, chronic esophagitis is caused by stasis of swallowed food and saliva. In this environment, the overgrowth of aerobic and anaerobic bacteria, including nitrate-reducing bacteria, is observed. The reduction of nitrate into nitrite by the action of these bacteria has been associated with the formation of volatile nitrosamines in different situations of gastric bacterial overgrowth. We have hypothesized that this phenomenon could occur in the esophageal lumen of patients with megaesophagus. To evaluate the concentration of nitrite, the presence of volatile nitrosamines and the concentration of nitrate-reducing bacteria in the esophageal lumen of patients with non-advanced megaesophagus of Chagas' disease and in a group of patients without esophageal disease. Fifteen patients with non-advanced megaesophagus [megaesophagus group (MG)] and 15 patients without any esophageal disease [control group (CG)] were studied. Saliva samples were taken for nitrate and nitrite quantitative determination and esophageal stasis liquid samples were taken for nitrate and nitrite quantitative determination, volatile nitrosamines qualitative determination and reductive bacteria quantitative determination. MG and CG were equivalent in nitrate and nitrite saliva concentration and in nitrate esophageal concentration. Significant difference was found in nitrite (p = 0.003) and reductive bacteria concentration (p < 0.0001), both higher in MG. Volatile nitrosamines were identified in three MG patients and in none of the CG patients, but this was not significant (p = 0.113). There is a higher concentration of reductive bacteria in MG, responsible for the rise in nitrite concentration at the esophageal lumen and, eventually, for the formation of volatile nitrosamines.

Apoptosis and autoimmunity as proposed pathogenetic links between Helicobacter pylori infection and idiopathic achalasia.

Achalasia is a disorder of the oesophagus characterised by increased lower oesophageal sphincter (LOS) tone, lack of LOS relaxation with swallowing and aperistalsis of the body of the oesophagus. The aetiology and pathogenesis of idiopathic achalasia are still unclear, although a viral cause, genetic influences (associations with HLA loci) and autoimmune processes have been postulated. Degeneration and significant loss of nerve fibres, associated with an inflammatory infiltrate of the myenteric plexus in idiopathic achalasia, provide evidence of an immune mediated destruction of the myenteric plexus, possibly through apoptotic process. This concept is reinforced by the concomitant appearance of achalasia and Guillain-Barré syndrome (GBS) and/or Parkinson's disease, where inappropriate initiation of apoptosis has been proposed to underlie the neuronal attrition. In the same respect, Helicobacter pylori (H. pylori) infection has been associated with gastric autoimmunity, and patients infected with H. pylori have been shown to possess autoantibodies that cross-react with antigens expressed on the gastric mucosa. Furthermore, H. pylori is thought to be associated with the development of autoimmune sequelae observed in peripheral neuropathies and GBS, where autoantibodies to specific neural targets have been found to impair native neural function by inducing nerve tissue damage, possibly by apoptosis. Taken together, we assume that H. pylori infection might be a pathogenetic factor of achalasia through induction of autoimmunity and apoptosis. Whether eradication of H. pylori infection may indirectly offer benefit to the pathophysiology of idiopathic achalasia by ameliorating the apoptotic loss of ganglion cells and their axons in the oesophageal wall remains to be elucidated.

[Megaesophagus microbiota and carcinogenesis]. / Microbiota do megaesôfago e carcinogênese.

BACKGROUND: The risk of development of spin cell carcinoma of the esophagus is 33 times higher in patients with chagasic achalasia. It is possible that the production of N-nitroso compounds in the esophageal lumen by of bacterial action in the stasis liquid that reduce nitrates from diet into nitrites may play a role in this process. AIM: To analyze qualitatively and quantitatively the microbiota in chagasic megaesophagus with special attention to bacteria capable of transforming nitto reduction. PATIENTS: Fifteen patients (six men and nine women) were prospectively studied, with ages varying from 28 to 73 years. Patients were divided into three sub-groups according to Rezende et al. classification of esophageal dilation (grade I, grade II and grade III). METHOD: The sample collection was performed using a method specially developed to avoid contamination with microorganisms of the oral cavity and oropharynx, using a Levine catheter n 14 and a 7,5 oro-traqueal tube. RESULTS: Ninety three point three percent of the cultures were positive, with great bacterial variability and predominance of a variety of aerobic Gram-positive and anaerobic bacteria. The bacterial concentrations were generally more elevated in grade III in comparison to grade I and grade II. Among the microorganisms found, Staphylococcus sp, Corynebacterium sp, Peptostreptococcus sp e a Veillonella sp were those with the capability of nitrate reduction. CONCLUSION: It was concluded that patients with megaesophagus present some bacteria in the esophageal lumen that are able to reduce nitrates intro nitrites, an important step in the formation of N-nitroso compounds.

Microbiota do megaesôfago e carcinogênese / Megaesophagus microbiota and carcinogenesis

INTRODUÇAO: O risco de desenvolvimento de carcinoma esofágico em portadores de megaesôfago é 33 vezes superior ao da populaçäo em geral. Possível explicaçäo para este fenômeno poderia estar relacionada à produçäo de compostos N-nitrosos na luz do órgäo, a partir da transformaçäo de nitratos da dieta em nitritos, mediada por bactérias em suspensäo no líquido de estase e com o contato crônico destes carcinógenos com a mucosa esofágica. OBJETIVO: Analisar a microbiota esofágica em pacientes portadores de megaesôfago de etiologia chagásica, com especial atençäo para a presença de bactérias com capacidade de reduçäo de nitratos. CASUíSTICA: Foram estudados prospectivamente 15 pacientes portadores de megaesôfago chagásico com idades variando de 28 a 73 anos, sendo 9 do sexo feminino e 6 do sexo masculino, que foram divididos em 3 grupos iguais de 5, de acordo com o grau de dilataçäo do esôfago, segundo a classificaçäo de Rezende et al. (Grau I, Grau II e Grau III). MÉTODO: A coleta do líquido de estase para estudo microbiológico era realizada através de sonda de Levine nº 14, que era passada pela boca, por dentro de uma cânula de intubaçäo orotraqueal nº 7,5, mantendo-se sua extremidade escondida, a fim de evitar sua contaminaçäo. RESULTADOS: Foram obtidas 93,3 por cento de culturas positivas com grande variedade de microrganismos e predomínio de aeróbios Gram-positivos e anaeróbios. As concentrações de microrganismos foram tanto maiores, quanto maior o grau de dilataçäo do esôfago. Entre os microrganismos encontrados, o Staphylococcus sp, Corynebacterium sp, Peptostreptococcus sp e a Veillonella sp foram aqueles identificados como tendo a capacidade de reduçäo de nitratos a nitritos. CONCLUSÄO: No megaesôfago chagásico há bactérias na luz do órgäo com capacidade de reduçäo de nitratos da dieta, passo importante na produçäo de compostos N-nitrosos.

Cryptococcal pyelonephritis in a dog.

A 5-year-old castrated male Golden Retriever was evaluated for polyuria, polydipsia, and progressive regurgitation thought to be a result of bacterial pyelonephritis and megaesophagus. Bacteriologic culture of urine failed to yield clinically relevant growth, and results of a urine sediment examination were normal. With time, intention tremors and progressive neurologic dysfunction were also observed. At necropsy, a diagnosis of cryptococcal disease was confirmed histologically and immunohistochemically. Findings in the dog of this report were indicative of nephrogenic diabetes insipidus with polyuria and polydipsia caused by cryptococcal pyelonephritis. Neurologic manifestations of systemic cryptococcus infection included megaesophagus, esophageal hypomotility, and regurgitation attributed to localization of cryptococcal organisms in the brain stem in the region of the dorsal motor nucleus of the vagus nerve. To the authors' knowledge, this is the first report of polyuria secondary to cryptococcal pyelonephritis.

Megaesophagus microbiota: a qualitative and quantitative analysis.

Bacterial overgrowth in the esophageal lumen in patients with megaesophagus can be the cause of recurring pulmonary infections, infectious complications due to surgical or endoscopic procedures, and the development of dysplasia of the esophageal mucosa and cancer. Despite this, esophageal microbiota in the megaesophagus have never been studied. The aim of this study was to analyze qualitatively and quantitatively the microbiota in chagasic megaesophagus in comparison to the normal esophagus. Twenty-five patients (10 men and 15 women), ranging in age from 24 to 74 years (mean years), were prospectively studied from March to September 2000. Fifteen patients with chagasic megaesophagus were divided into three subgroups (n = 5 patients in each) according to the grade of esophageal dilation: MG1 = megaesophagus grade I; MG2 = megaesophagus grade II; and MG3 = megaesophagus grade III. Another group of 10 patients without esophageal disease served as a control group. Samples were collected using a method especially developed to avoid contamination with microorganisms of the oral cavity and oropharynx. In the control group, 40% of the cultures were positive with the genus Streptococcus predominating and concentrations varying from 10(1) to 10(2) colony-forming units/ml. In the megaesophagus group, 93.3% of the cultures were positive, with great variability in the bacteria and a predominance of various aerobic gram-positive bacteria (Streptococcus was most common) and anaerobic bacteria (Veillonella was most frequent) in concentrations that ranged from 10(1) to 10(5) colony-forming units/ml. The bacterial concentrations were generally more elevated in MG3 patients in comparison to MG1 and MG2 patients and the control group (P < 0.05). It was concluded that patients with megaesophagus have a variety of microbiota consisting mostly of aerobic gram-positive and anaerobic bacteria, in concentrations that varied according to the degree of esophageal dilation.

[Microflora in chagasic megaesophagus]. / Estudo da microflora do megaesôfago chagásico.

Chagasic patients with megaesophagus were submitted to an endoscopy of the upper digestive tract and the samples were collected with special instruments under sterilized conditions. One of the four samples collected was from the stase liquid and the other three samples were collected from fragments of the esophageal mucosa at one, three and five centimeters from the esophageal-stomach transition (Z line). The samples were analyzed by the Microbiology and Pathologic labs for the identification of microorganisms. After that, the results were correlated with the degree of mega esophagus according to Ferreira-Santos. We observed that the incidence of pathogenic microorganism is very high in megaesophagus, with no relation with the degree of dilatation making the surgery for the treatment of this affection potentially contaminated. There was no significant difference concerning the positivity of the culture relating to the degree of esophagus dilatation.

Estudo da microflora do megaesofago chagásico / Microflora in chagasic megaesophagus

Chagasic patients with megaesophagus were submitted to an endoscopy of the upper digestive tract and the samples were collected with special instruments under sterilized conditions. One of the four samples collected was from the stase liquid and the other three samples were collected from fragments of the esophageal mucosa at one, three and five centimeters from the esophageal-stomach transition (Z line). The samples were analyzed by the Microbiology and Pathologic labs for the identification of microorganisms. After that, the results were correlated with the degree of mega esophagus according to Ferreira-Santos. We observed that the incidence of pathogenic microorganism is very high in megaesophagus, with no relation with the degree of dilatation making the surgery for the treatment of this affection potentially contaminated. There was no significant difference concerning the positivity of the culture relating to the degree of esophagus dilatation.

Achalasia: a critical review of epidemiological studies.

Achalasia is one of the earliest recognized gastroenterological conditions. However, several centuries after it was first described, it remains also among the least understood. One of the main reasons for this is the relative rarity of the disease, which has resulted in limited opportunities to conduct investigative research. Few epidemiological studies have been conducted to date, and their data suggest a worldwide incidence estimated at between 0.03-1.1/10(5)/yr. This review of the literature on the epidemiology of achalasia lends support to the idea that pooling of resources and collaboration at an international level is required, if any significant progress in the cause, treatment, and prevention of the disease is to be made.

Are human herpes viruses or measles virus associated with esophageal achalasia?

In order to test the hypothesis that esophageal achalasia may be due to neurotropic viral damage to the esophageal myenteric plexus, esophageal tissue with or without achalasia was analyzed by polymerase chain reaction for the presence of human herpes virus DNA or measles virus RNA. The DNA and RNA were extracted from the esophageal muscle of 12 patients with achalasia and six patients with upper esophageal carcinoma. Peripheral blood mononuclear cells from eight adult volunteers and two samples of umbilical blood mononuclear cells were also used as controls. PCR amplification with a pair of primers specific for herpes simplex type 1 and 2 viruses identified 92-bp fragments in nearly all specimens, including those without achalasia. Each 92-bp fragment was confirmed to be identical to a single herpes simplex virus sequence by automated DNA sequence analysis. No amplification for five other herpes viruses or measles virus was detected. Therefore, a specific viral etiology for achalasia was not identified in this study.

Flora do delgado em megas chagásicos: estudo pelo teste do H2 respiratório / Small intestine flora in chagasic megas: study by H2 breath test

O teste do H2 respiratório é utilizado para estudar a flora do delgado de chagásicos portadores de megaesôfago e/ou megacólon. Compara-se com um grupo controle assintomático, demonstando um aumento significante (P < 0,05) da flora do delgado no grupo chagásico. Conclui-se que o teste usado se mostrou útil na detecçäo da flora intestinal alterada, podendo ser empregado como uma alternativa simples à cultura de suco entérico

[Small intestine flora in chagasic patients with megaesophagus and/or megacolon: study using the H2 breath test]. / Flora do delgado em megas chagásicos: estudo pelo teste do H2 respiratório.

The author use the H2 breath test to study the small bowel microflora of chagasic patients with megaesophagus and/or megacolon. Compare this group with a control one. Find a significant increase (P < 0.05) in the small bowel flora of chagasic group. It is concluded that H2 breath is a simple and useful test to detect alteration in intestinal flora.

Guillain-Barre syndrome and achalasia: two manifestations of a viral disease or coincidental association?

Guillain-Barre' syndrome and achalasia are rare diseases of uncertain cause. However, viral etiologies have been postulated for each disorder. The concomitant presence of both disorders in a patient suggests a common etiology, because a coincidental association would be exceedingly rare. Indeed, to our knowledge, the concomitant appearance of Guillain-Barre' syndrome and achalasia has not been previously reported. We now report our observation of a patient who developed dysphagia shortly after onset of Guillain-Barre' syndrome. Achalasia was subsequently diagnosed by manometry and was successfully treated by pneumatic dilation. The concomitant appearance of Guillain-Barre' syndrome and achalasia in our patient supports the notion of a viral etiology for achalasia.

Varicella-zoster virus DNA in the oesophageal myenteric plexus in achalasia.

In a search for past or present infection with herpes viruses, serum antibody titres to herpes simplex type 1 virus, cytomegalovirus, and varicella-zoster virus were measured by complement fixation test in 58 patients with achalasia. Serum was also taken from 40 age and sex matched patients without oesophageal symptoms who formed a control group. All titres were low, and those for herpes simplex type 1 virus and cytomegalovirus did not differ in the achalasia patients and the controls. However, the incidence of varicella-zoster virus antibodies was significantly greater in the achalasia than in the control group (p < 0.05). Using oesophageal tissue containing myenteric plexus removed at the time of cardiomyotomy in nine patients with achalasia, in situ DNA hybridisation showed evidence of varicella-zoster virus in three, but all were negative for the other two viruses. No positive results were obtained for herpes simplex type 1 virus, cytomegalovirus, or varicella-zoster virus in oesophageal tissue from 20 patients undergoing oesophageal resection for diseases other than achalasia. The incidence of positivity for varicella-zoster virus was significantly increased in the achalasia group compared with the controls (p < 0.02). The findings indicate that varicella-zoster virus DNA may persist in the oesophageal myenteric plexus in some patients with achalasia and raise the possibility that this virus is of aetiological importance in achalasia.