Trimethylamine N-oxide and kidney diseases: what do we know? / N-óxido de trimetilamina e doenças renais: o que sabemos?

Abstract In the human gut, there is a metabolically active microbiome whose metabolic products reach various organs and are used in the physiological activities of the body. When dysbiosis of intestinal microbial homeostasis occurs, pathogenic metabolites may increase and one of them is trimethyl amine-N-oxide (TMAO). TMAO is thought to have a role in the pathogenesis of insulin resistance, diabetes, hyperlipidemia, atherosclerotic heart diseases, and cerebrovascular events. TMAO level is also associated with renal inflammation, fibrosis, acute kidney injury, diabetic kidney disease, and chronic kidney disease. In this review, the effect of TMAO on various kidney diseases is discussed.

Resumo No intestino humano, existe um microbioma metabolicamente ativo cujos produtos metabólicos alcançam diversos órgãos e são utilizados nas atividades fisiológicas do corpo. Quando ocorre disbiose da homeostase microbiana intestinal, os metabólitos patogênicos podem aumentar, e um deles é o N-óxido de trimetilamina (TMAO). Acredita-se que o TMAO tenha um papel na patogênese da resistência à insulina, diabetes, hiperlipidemia, doenças cardíacas ateroscleróticas e eventos cerebrovasculares. O nível de TMAO também está associado à inflamação renal, fibrose, lesão renal aguda, doença renal diabética e doença renal crônica. Nesta revisão, discute-se o efeito do TMAO em diversas doenças renais.

Isolation and characterization of bacteria associated with silkworm gut under antibiotic-treated larval feeding / Isolamento e caracterização de bactérias associadas ao trato intestinal do bicho-da-seda sob alimentação larval tratada com antibióticos

Abstract The impact of antibiotics on growth, cocoon production was assessed in addition to isolation and characterization of bacteria associated with silkworm gut of infected larvae. Larval rearing was maintained at recommended conditions of temperature and humidity. Silkworm larvae showing abnormal symptoms were collected from the control group and dissected for gut collection. Bacteria were isolated from the gut content by spreading on agar plates and incubated at 37 °C for 48 hrs. Bacterial identification and phylogenetic analysis were carried out by 16S rRNA gene sequencing. The isolated bacteria were subjected to antimicrobial susceptibility test (disc diffusion methods) by using Penicillin (10 µg/mL), Tetracycline (30 µg/mL), Amoxicillin (25 µg/mL), Ampicillin (10 µg/mL), and Erythromycin (15 µg/mL). All isolated strains showed positive results for the catalase test. We isolated and identified bacterial strains (n = 06) from the gut of healthy and diseased silkworm larvae. Based on the 16S rRNA gene sequence, isolated bacteria showed close relation with Serratia, Bacillus, and Pseudomonas spp. Notably, 83.3% of strains were resistant to Penicillin, Tetracycline, Amoxicillin, Ampicillin, and Erythromycin but 16.6% showed antibiotic susceptibility to the above-mentioned commonly used antibiotics. Silkworm larvae fed on penicillin-treated leaves showed significant improvement in larval weight, larval length, and cocoon production. Significantly higher larval weight (6.88g), larval length (5.84cm), and cocoon weight (1.33g) were recorded for larvae fed on leaves treated with penicillin as compared to other antibiotics. Isolated bacterial strains showed close relation with Serratia spp., Bacillus spp. and Pseudomonas spp.

Resumo O impacto dos antibióticos no crescimento e na produção do casulo foi avaliado, além do isolamento e caracterização das bactérias associadas ao intestino de larvas infectadas do bicho-da-seda. A criação das larvas foi mantida nas condições recomendadas de temperatura e umidade. As larvas do bicho-da-seda com sintomas anormais foram coletadas do grupo controle e dissecadas para coleta do intestino. As bactérias foram isoladas do conteúdo intestinal por espalhamento em placas de ágar e incubadas a 37° C durante 48 horas. A identificação bacteriana e a análise filogenética foram realizadas pelo sequenciamento do gene 16S rRNA. As bactérias isoladas foram submetidas a teste de sensibilidade antimicrobiana (métodos de difusão em disco) com penicilina (10 µg / mL), tetraciclina (30 µg / mL), amoxicilina (25 µg / mL), ampicilina (10 µg / mL) e eritromicina (15 µg / mL). Todas as cepas isoladas apresentaram resultados positivos para o teste da catalase. Isolamos e identificamos cepas bacterianas (n = 06) do intestino de larvas de bicho-da-seda saudáveis e doentes. Com base na sequência do gene 16S rRNA, as bactérias isoladas mostraram estreita relação com Serratia, Bacillus e Pseudomonas spp. Notavelmente, 83,3% das cepas eram resistentes a penicilina, tetraciclina, amoxicilina, ampicilina e eritromicina, mas 16,6% mostraram suscetibilidade aos antibióticos comumente usados mencionados acima. As larvas do bicho-da-seda alimentadas com folhas tratadas com penicilina apresentaram melhora significativa no peso larval, comprimento larval e produção de casulo. Peso larval significativamente maior (6,88g), comprimento larval (5,84cm) e peso do casulo (1,33g) foram registrados para larvas alimentadas com folhas tratadas com penicilina, em comparação com outros antibióticos. Cepas bacterianas isoladas mostraram estreita relação com Serratia spp., Bacillus spp. e Pseudomonas spp.

The combination of berberine and cinnamon polyphenol can improve glucose metabolism in T2DM rats through Bas-TGR5-GLP-1 / 药学学报

Berberine (BBR) is the main pharmacological active ingredient of Coptidis, which has hypoglycemic effect, but its clinical application is limited due to its poor oral bioavailability. Polyphenols, derived from cinnamon, are beneficial for type 2 diabetes mellitus (T2DM). The combination of both may have an additive effect. The aim of this study was to investigate the hypoglycemic effect and mechanism of combined medication in diabetic rats. The modeling rats were randomly divided into 5 groups (berberine group, cinnamon group, combined group, metformin group, diabetic control group) and normal control group. The animal experiments were approved by the Animal Ethics Committee (approval number: HMUIRB2022003). The subjects were given orally, and the control group was given equal volume solvent and body weight was measured weekly. Thirty days after administration, oral glucose tolerance test and insulin sensitivity test were performed, and fasting blood glucose (FBG), glycated serum protein (GSP), and serum insulin (INS) levels were detected; high-throughput sequencing technology was used to detect intestinal microbiota structure; real-time quantitative PCR (RT-qPCR) and Western blot were used to detect G protein-coupled receptor 5 (TGR5) and glucagon-like peptide-1 (GLP-1) expression levels. The results showed that, compared with the diabetic control group, the levels of FBG (P < 0.01) and GSP (P < 0.01) in the combined group were lower, and the insulin resistance was improved, which was better than that in the berberine group. Combined treatment increased the relative abundance of Bacteroides, Prevotella and Lactobacillus, reversed the decrease in Lactobacillus in the berberine alone induction group, and the combination of the two could promote the expression of TGR5 and GLP-1. In summary, the combined application of cinnamon and berberine can regulate glucose metabolism better than the application of berberine alone. Berberine combined with cinnamon can improve the function of pancreatic islet β cells in diabetes mellitus type 2 rats by changing the intestinal microbiota, increasing the expression of TGR5 and GLP-1 proteins, and thereby better regulating glucose metabolism.

Mechanism of Flavonoids in Patriniae Herba in Affecting Occurrence and Development of Colorectal Cancer / 中国实验方剂学杂志

Colorectal cancer is a common malignant tumor in the digestive system， ranking third in incidence and second in the cause of death worldwide. In recent years， the incidence of colorectal cancer is on the rise， and the age of patients with colorectal cancer tends to be younger， with a heavy cancer burden. It is of great significance to prevent the occurrence， development， recurrence， and metastasis of colorectal cancer to reduce the incidence and mortality of colorectal cancer. Patriniae Herba has the effects of clearing heat， removing toxins， eliminating carbuncle， and discharging pus and shows good therapeutic efficacy on inflammatory bowel disease， digestive tract tumors， pelvic inflammation， gynecological tumor， and so on. Patriniae Herba is often used in the clinical treatment of colorectal cancer， but its mechanism of action is not clear. Modern studies have found that Patriniae Herba contains triterpenoids， saponins， iridoids， flavonoids， and other chemical components， with antioxidant， anti-tumor， anti-bacterial， and other pharmacological effects. The main anti-tumor components of Patriniae Herba are flavonoids. The analysis of network pharmacology and the spectrum-effect relationship has suggested that quercetin， luteolin， apigenin， isoorientin， and isovitexin play a major role in inhibiting the occurrence and development of colorectal cancer. In vivo and in vitro studies have shown that flavonoids in Patriniae Herba can play an anti-tumor role in various ways， such as preventing precancerous lesions of colorectal cancer， inhibiting the growth and proliferation of cancer cells， blocking cancer cell cycle， promoting cancer cell apoptosis， and reversing drug resistance of colorectal cancer. The oral availability of flavonoids is low. The gut is the main metabolic site of flavonoids in the body， its metabolic pathway is closely related to gut microbiota. This paper reviewed the anti-tumor mechanism of flavonoids and their influence on gut microbiota to provide a reference for further research on the mechanism of Patriniae Herba against colorectal cancer and its clinical application.

Connotation of Traditional Chinese Medicine in Treatment of Chronic Obstructive Pulmonary Disease by Regulating Gut Microbiota Based on "Lung and Large Intestine Being Interior-exterior Related" / 中国实验方剂学杂志

Chronic obstructive pulmonary disease （COPD） is a heterogeneous lung condition characterized by persistent and often progressive airflow obstruction， including airway abnormalities （e.g.， bronchitis and bronchiolitis） and chronic respiratory symptoms （e.g.， dyspnea， cough， and expectoration）. It is one of the leading causes of death worldwide. According to the theory of traditional Chinese medicine （TCM）， the lung and large intestine are interior-exterior related. Therefore， COPD can be treated from both the lung and intestine by the methods of tonifying and invigorating lung， spleen， and kidney， dispelling phlegm， and expelling stasis. Gut microbiota plays a key role in human immunity， nerve， and metabolism and may act on COPD by affecting the structures and functions of lung and intestine tissue and regulating lung inflammation and immunity. TCM can restore the balance of gut microbiota， which is conducive to the recovery from COPD. For example， the treatment method of tonifying lung and invigorating kidney can regulate gut microbiota， alleviate pulmonary and intestinal injuries， and improve lung immunity. The treatment methods of dispelling phlegm and expelling stasis can regulate gut microbiota and reduce pulmonary inflammation. According to the TCM theory of lung and large intestine being interior-exterior related， this review elaborates on the connotation of TCM in the treatment of COPD by regulating gut microbiota， aiming to provide new ideas for the clinical treatment of COPD via gut microbiota.

Isolation and characterization of bacteria associated with silkworm gut under antibiotic-treated larval feeding

Abstract The impact of antibiotics on growth, cocoon production was assessed in addition to isolation and characterization of bacteria associated with silkworm gut of infected larvae. Larval rearing was maintained at recommended conditions of temperature and humidity. Silkworm larvae showing abnormal symptoms were collected from the control group and dissected for gut collection. Bacteria were isolated from the gut content by spreading on agar plates and incubated at 37 °C for 48 hrs. Bacterial identification and phylogenetic analysis were carried out by 16S rRNA gene sequencing. The isolated bacteria were subjected to antimicrobial susceptibility test (disc diffusion methods) by using Penicillin (10 µg/mL), Tetracycline (30 µg/mL), Amoxicillin (25 µg/mL), Ampicillin (10 µg/mL), and Erythromycin (15 µg/mL). All isolated strains showed positive results for the catalase test. We isolated and identified bacterial strains (n = 06) from the gut of healthy and diseased silkworm larvae. Based on the 16S rRNA gene sequence, isolated bacteria showed close relation with Serratia, Bacillus, and Pseudomonas spp. Notably, 83.3% of strains were resistant to Penicillin, Tetracycline, Amoxicillin, Ampicillin, and Erythromycin but 16.6% showed antibiotic susceptibility to the above-mentioned commonly used antibiotics. Silkworm larvae fed on penicillin-treated leaves showed significant improvement in larval weight, larval length, and cocoon production. Significantly higher larval weight (6.88g), larval length (5.84cm), and cocoon weight (1.33g) were recorded for larvae fed on leaves treated with penicillin as compared to other antibiotics. Isolated bacterial strains showed close relation with Serratia spp., Bacillus spp. and Pseudomonas spp.

Resumo O impacto dos antibióticos no crescimento e na produção do casulo foi avaliado, além do isolamento e caracterização das bactérias associadas ao intestino de larvas infectadas do bicho-da-seda. A criação das larvas foi mantida nas condições recomendadas de temperatura e umidade. As larvas do bicho-da-seda com sintomas anormais foram coletadas do grupo controle e dissecadas para coleta do intestino. As bactérias foram isoladas do conteúdo intestinal por espalhamento em placas de ágar e incubadas a 37° C durante 48 horas. A identificação bacteriana e a análise filogenética foram realizadas pelo sequenciamento do gene 16S rRNA. As bactérias isoladas foram submetidas a teste de sensibilidade antimicrobiana (métodos de difusão em disco) com penicilina (10 µg / mL), tetraciclina (30 µg / mL), amoxicilina (25 µg / mL), ampicilina (10 µg / mL) e eritromicina (15 µg / mL). Todas as cepas isoladas apresentaram resultados positivos para o teste da catalase. Isolamos e identificamos cepas bacterianas (n = 06) do intestino de larvas de bicho-da-seda saudáveis e doentes. Com base na sequência do gene 16S rRNA, as bactérias isoladas mostraram estreita relação com Serratia, Bacillus e Pseudomonas spp. Notavelmente, 83,3% das cepas eram resistentes a penicilina, tetraciclina, amoxicilina, ampicilina e eritromicina, mas 16,6% mostraram suscetibilidade aos antibióticos comumente usados mencionados acima. As larvas do bicho-da-seda alimentadas com folhas tratadas com penicilina apresentaram melhora significativa no peso larval, comprimento larval e produção de casulo. Peso larval significativamente maior (6,88g), comprimento larval (5,84cm) e peso do casulo (1,33g) foram registrados para larvas alimentadas com folhas tratadas com penicilina, em comparação com outros antibióticos. Cepas bacterianas isoladas mostraram estreita relação com Serratia spp., Bacillus spp. e Pseudomonas spp.

Papel de la plasticidad celular en la regeneración intestinalinducida por lesiones / Role of cell plasticity in injury-induced intestinal regeneration

El sistema intestinal posee una capacidad regenerativa intrínseca y fisiológica que tiene lugar a partir de las células madreLgr5+ ubicadas en el fondo de las criptas intestinales, las cuales se diferencian hacia las células progenitoras secretoras y absortivas con sus respectivas células especializadas mediante la activación de señalizaciones intracelulares como Wnt, Hippo y Notch. Condiciones adversas como lesiones e infecciones tisulares inducen esta actividad regenerativa promovida por variados mecanismos que influyen en el microambiente celular. El sistema inmunológico detecta alteraciones en el tejido intestinal y, a través de la activación de células inmunocompetentes y la secreción de citoquinas proinflamatorias, favorece la desdiferenciación de células especializadas hacia células madre para desencadenar la respuesta regenerativa. En cuanto al sistema nervioso entérico, su influencia está sujeta a modificaciones en la microbiota y los hábitos alimenticios, y se encuentra determinada en gran parte, por las células gliales entéricas y la expresión de distintos marcadores de plasticidad, que permiten limitar la lesión y reparar el tejido. Por su parte, la epigenéticamodifica la expresión genética y consecuentemente, la capacidadregenerativa intestinal, variando de acuerdo a cada paciente porla influencia de factores externos como la dieta o el estadopsicobiológico. De esta forma, la respuesta regenerativa intestinalinducida por lesiones, integra múltiples mecanismos y poseeimportantes repercusiones clínicas en cuanto a EII, disbiosise incluso tumorogénesis; conocer los mecanismos que regulanesta actividad puede sentar las bases para la creación de terapias innovadoras en el mismo ámbito(AU)

The intestinal system has an intrinsic and physiological regenerative capacity that takes place from the Lgr5+ stem cells located at the bottom of the intestinal crypts, which differentiate into secretory and absorptive progenitor cells with their specialized cells by activating intracellular signalslike Wnt, Hippo and Notch. Adverse conditions such asinjuries and tissue infections induce this regenerative activity promoted by various mechanisms that influence the cellular microenvironment. The immune system senses disturbances in the intestinal tissue and, through the activation of immunocompetent cells and the secretion of proinflammatorycytokines, favors the dedifferentiation of specialized cells intostem cells to trigger the regenerative response. Regarding theenteric nervous system, its influence is subject to modificationsin the microbiota and dietary habits, and is largely determinedby enteric glial cells and the expression of different plasticitymarkers, which enable to limit injuries and repair tissue. On the other hand, epigenetics modifies genetic expressionand, consequently, intestinal regenerative capacity, varying according to each patient due to the influence of external factors such as diet or psychobiological status. There fore, the intestinal regenerative response induced by lesions integrates multiple mechanisms and has important clinical repercussions in terms of IBD, dysbiosis, and even tumorigenesis; knowing themechanisms that regulate this activity can lay the foundations for the creation of innovative therapies in the same field (AU)

Capsaicin fails to produce changes in contractile tension in large gut of neonate rats

Objectives: Capsaicin, the most pungent constituent of chilli pepper (Capsicum annuum L.), is known to alter the physiological activity of the gut. Capsaicin mediates its action through a transient receptor potential vanilloid type 1 (TRPV1) channel. The action of capsaicin on gut smooth muscle varies from segment to segment in different species. The earlier studies were carried out in adult animals only, and its status in the neonate gut, which is in a development stage, is not known. Objective: Therefore, the present study was done to assess the effect of capsaicin on the large gut of neonates. Materials and Methods: In an organ bath preparation, isometric contractions were recorded from segments of dissected rat colon and rectum. The gut segments were exposed to cumulative concentrations of capsaicin (0.01 nM–3 µM) and a capsaicin-induced contractile response was observed. TRPV1 receptor antagonist capsazepine (1 µM) and a nitric oxide synthase inhibitor, L-NAME (100 µM), were used to assess their blocking effect on capsaicin-induced contractile response. Results: Capsaicin raised contractile tension in the colon and rectum of adult rats but not in neonate rats. In adult rats, capsazepine pre-treatment (1 µM) failed to block the capsaicin-induced response in the colon, but in the lower concentrations, it increased contractile tension in the rectum. Pre-application of L-NAME (100 µM) potentiated capsaicin-induced response in the adult rectum and neonate’s colon but had no effect in the neonate rectum and adult colon. Capsaicin with a low concentration (0.01 nM–0.01 µM) increased contractile frequency in both the colon and rectum of adult rats. However, the effect of capsaicin on frequency was abolished at higher concentrations (0.01 µM–3 µM). A capsaicin-evoked change in contractile frequency in adult rats was blocked by capsazepine and L-NAME. At lower concentrations (0.01 nM–0.01 µM), capsaicin did not show any change in frequency in the neonatal colon, while a decrease in contractile frequency was observed with the higher concentrations (0.1 µM–3 µM) of capsaicin. In neonates, capsazepine pre-treatment produced changes in frequency for both the colon and rectum. However, pre-application of L-NAME decreased frequency in the neonate rectum but not in the colon. Conclusion: Capsaicin-induced changes in contractile activity may or may not involve TRPV1 or the Nitric Oxide (NO) pathway, depending on the part of the large gut and developmental maturity.

A Deep Insight into the Correlation Between Gut Dysbiosis and Alzheimer’s Amyloidopathy

Recent research has shown a strong correlation between gut dysbiosis and Alzheimer’s disease (AD). The purpose of this review is to investigate the relationship between gut dysbiosis, immune system activation, and the onset of AD and to examine current breakthroughs in microbiota-targeted AD therapeutics. A review of scientific literature was conducted to assess the correlation between gut dysbiosis and AD and the various factors associated. Gut dysbiosis produces an increase in harmful substances, such as bacterial amyloids, which makes the gut barrier and blood-brain barrier more permeable. This leads to the stimulation of immunological responses and an increase in cytokines such as interleukin-1? (IL-1?). As a result, gut dysbiosis accelerates the progression of AD. The review highlights the connection between gut dysbiosis and AD and the potential for microbiota-targeted therapies in AD treatment.

Brief review of pathophysiological disorders as consequence of psychological stress / Breve revisión de los trastornos fisiopatológicos como consecuencia del estrés psicológico

Background: Psychological stress is a reaction to an unexpected situation that favours adaptation and response to the event. However, when psychological stress is chronic or very intense, it can induce changes in various systems and tissues, causing diseases or aggravating existing ones. Objective: To briefly analyse the pathophysiological conditions caused by psychological stress. Method: A narrative review of the scientific literature on pathophysiological conditions as a consequence of psychological stress was performed. Results: Psychological stress can induce various conditions at the gastrointestinal, immune and cardiovascular levels. This is mainly due to the neurobiological and endocrine response because when faced with a stressful stimulus, a deregulated release of glucocorticoids and catecholamines is generated, altering the normal physiology of the organism. Gastrointestinal disorders are mainly due to goblet cell dysfunction, resulting in intestinal hyperpermeability, inflammation and infection. Changes at the immune level lead to an increase in inflammatory responses but a decrease in the protective activities of the immune system. Finally, cardiovascular conditions include atherosclerosis, increased blood pressure and stroke. Conclusion: Psychological stress can induce real physiological pathologies and, in some cases, fatal ones. Some of the molecular mechanisms involved in these pathologies have already been studied and identified. Knowledge of these molecular mechanisms can help clinicians and therapists to improve the treatment and therapy of patients.

Introducción: El estrés psicológico es una respuesta a una situación inesperada que favorece la adaptación y la respuesta ante dicho evento. Sin embargo, cuando el estrés psicológico es crónico o muy intenso, se pueden desencadenar afecciones en diversos sistemas y tejidos, generando enfermedades o empeorando las ya existentes. Objetivo: Analizar brevemente las afecciones fisiopatológicas causadas por el estrés psicológico. Método: Se realizó una revisión narrativa con la literatura científica sobre las afecciones fisiopatológicas debidas al estrés psicológico. Resultados: El estrés psicológico puede desencadenar diversas afecciones a nivel gastrointestinal, inmunitario y cardiovascular. Esto se debe principalmente a la respuesta neurobiológica y endócrina, ya que ante estímulos estresores, se genera una liberación desregulada de glucocorticoides y catecolaminas que alteran la fisiología normal del organismo. Las afecciones a nivel gastrointestinal se deben principalmente a la disfunción de las células caliciformes, dando como consecuencia hiperpermeabilidad intestinal, inflamación e infecciones. Las alteraciones a nivel inmunitario generan un aumento en las respuestas inflamatorias pero una reducción en las actividades protectoras del sistema inmune. Por último, las afecciones cardiovasculares incluyen ateroesclerosis, aumento de la presión arterial y derrames cerebrales, entre otros. Conclusión: El estrés psicológico puede causar patologías fisiológicas reales y, en algunos casos, mortales. Algunos de los mecanismos moleculares implicados en estas patologías ya han sido estudiados y establecidos. Conocer estos mecanismos moleculares puede ayudar a los médicos y terapeutas a mejorar el tratamiento y la terapia del paciente.

Potential relationship between Tourette syndrome and gut microbiome

Abstract Objective: In this article, the author aims to discuss and review the relationship between gut microbiota and Tourette syndrome, and whether the change in gut microbiota can affect the severity of Tourette syndrome. Sources: Literature from PubMed, Google Scholar, and China National Knowledge Infrastructure was mainly reviewed. Both original studies and review articles were discussed. The articles were required to be published as of May 2022. Summary of the findings: Current studies on the gut microbiome have found that the gut microbiome and brain seem to interact. It is named the brain-gut-axis. The relationship between the brain-gut axis and neurological and psychiatric disorders has been a topic of intense interest. Tourette syndrome is a chronic neurological disease that seriously affects the quality of life of children, and there appears to be an increase in Ruminococcaceae and Bacteroides in the gut of patients with Tourette syndrome. After clinical observation and animal experiments, there appear to be particular gut microbiota changes in Tourette syndrome. It provides a new possible idea for the treatment of Tourette syndrome. Probiotics and fecal microbial transplantation have been tried to treat Tourette syndrome, especially Tourette syndrome which is not sensitive to drugs, and some results have been achieved. Conclusions: The relationship between gut microbiota and Tourette syndrome and how to alleviate Tourette syndrome by improving gut microbiota are new topics, more in-depth and larger sample size research is still needed.

A doença de Alzheimer e sua relação com o eixo microbiota-intestino-cérebro / Alzheimer's disease and its relationship with the microbiota-gut-brain axis

ABSTRACT Background: Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease, characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain. Several pathways enable bidirectional communication between the central nervous system (CNS), the intestine and its microbiota, constituting the microbiota-gut-brain axis. Objective: Review the pathophysiology of AD, relate it to the microbiota-gut-brain axis and discuss the possibility of using probiotics in the treatment and/or prevention of this disease. Methods: Search of articles from the PubMed database published in the last 5 years (2017 to 2022) structure the narrative review. Results: The composition of the gut microbiota influences the CNS, resulting in changes in host behavior and may be related to the development of neurodegenerative diseases. Some metabolites produced by the intestinal microbiota, such as trimethylamine N-oxide (TMAO), may be involved in the pathogenesis of AD, while other compounds produced by the microbiota during the fermentation of food in the intestine, such as D-glutamate and fatty acids short chain, are beneficial in cognitive function. The consumption of live microorganisms beneficial to health, known as probiotics, has been tested in laboratory animals and humans to evaluate the effect on AD. Conclusion: Although there are few clinical trials evaluating the effect of probiotic consumption in humans with AD, the results to date indicate a beneficial contribution of the use of probiotics in this disease.

RESUMO Contexto: A doença de Alzheimer (DA) é uma doença neurodegenerativa progressiva e irreversível, caracterizada pelo acúmulo de placas amiloides e emaranhados neurofibrilares no cérebro. Diversas vias possibilitam uma comunicação bidirecional entre o sistema nervoso central (SNC), o intestino e sua microbiota, constituindo o eixo microbiota-intestino-cérebro. Objetivo Revisar a fisiopatogenia da DA, relacioná-la com o eixo microbiota-intestino-cérebro e discutir sobre a possibilidade do uso de probióticos no tratamento e/ou prevenção desta doença. Métodos: Busca de artigos da base de dados PubMed publicados nos últimos 5 anos (2017 a 2022) para estruturar a revisão narrativa. Resultados A composição da microbiota intestinal influencia o SNC, resultando em modificações no comportamento do hospedeiro e pode estar relacionada com o desenvolvimento de doenças neurodegenerativas. Alguns metabólitos produzidos pela microbiota intestinal, como o N-óxido de trimetilamina (TMAO), podem estar envolvidos na patogênese da DA, enquanto, outros compostos produzidos pela microbiota durante a fermentação de alimentos no intestino, como o D-glutamato e os ácidos graxos de cadeia curta, são profícuos na função cognitiva. O consumo de microrganismos vivos benéficos à saúde, os probióticos, tem sido testado em animais de laboratório e humanos para avaliação do efeito na DA. Conclusão Embora haja poucos ensaios clínicos que avaliem o efeito do consumo de probióticos em humanos com DA, os resultados até o momento indicam uma contribuição benéfica do uso de probióticos nesta doença.

Cambios en la microbiota durante el embarazo: revisión narrativa / Changes in the microbiota during pregnancy: a narrative review

OBJETIVO: Evaluar la evidencia científica de los cambios en la microbiota durante el embarazo. METODOLOGÍA: Revisión de la bibliografía publicada entre el 2013 y el 2022 efectuada mediante la búsqueda de artículos científicos escritos en español e inglés resguardados en las bases de datos bibliográficas NICE, CENETEC-SALUD, BIREME y Portal OMS, OPS, Portal de Evidencias de la Biblioteca Virtual de Salud - BVS, LILACS, BIREME, EVIPNET, PubMed y Cochrane. La selección de artículos se basó en los descriptores: microbiota; embarazo-pregnancy; microbiota, gut microbiome, fetus-feto; microbiota, placenta; microbiota, combinadas entre sí con el operador boleano "and". RESULTADOS: Se identificaron 3038 posibles artículos y 137 se encontraron adecuados para el objetivo de la revisión en virtud de estar relacionados directamente con el embarazo y la microbiota. Se revisaron estudios transversales, ensayos, revisiones, cohortes, casos y controles, revisiones sistemáticas o matanálisis. CONCLUSIONES: La microbiota se encuentra en diversos tejidos u órganos que anteriormente se creían estériles durante el embarazo. Se sugiere que todos los cambios que implica esta etapa pueden influir en la microbiota de la madre y el feto. A pesar de las crecientes investigaciones en el área aún quedan preguntas por contestar para ayudar a solucionar el enigma de los cambios en la diversidad en las diferentes complicaciones del embarazo y saber si los probióticos tendrían efecto o no en la disminución del riesgo a padecerlas.

Abstract OBJECTIVE: to evaluate the scientific evidence on changes in the microbiota during pregnancy. METHODOLOGY: A review of the literature published between 2013 and 2022 was carried out through the search of scientific articles in Spanish and English in the bibliographic databases NICE, CENETEC-SALUD, BIREME AND PORTAL WHO, PAHO, Portal of Evidence of the Virtual Health Library - BVS, LILACS, BIREME, EVIPNET, PUBMED and COCHRANE. The selection of articles was based on the descriptors: Microbiota, pregnancy, Gut microbiome, Fetus-Microbiota, Placenta - Microbiota, combined with each other with the Boolean "and". RESULTS: A total of 3,038 possible articles were identified and 137 were found suitable for the objective of the review because they were directly related to pregnancy and microbiota. Cross-sectional studies, trials, reviews, cohorts, case-controls, systematic review, or meta-analysis were reviewed. CONCLUSIONS: Microbiota has been found in various tissues or organs that were previously believed to be sterile during pregnancy, and with this, it is suggested that all the changes that this stage entails can influence the maternal and fetal microbiota. However, despite the growing research in the area, there are still questions to be resolved to help solve the enigma of the changes in diversity in the different complications of pregnancy and whether the use of probiotics would influence reducing the risk to present them.

Heavy metal resistance in the Yanomami and Tunapuco microbiome

BACKGROUND The Amazon Region hosts invaluable and unique biodiversity as well as mineral resources. Consequently, large illegal and artisanal gold mining areas exist in indigenous territories. Mercury has been used in gold mining, and some has been released into the environment and atmosphere, primarily affecting indigenous people such as the Yanomami. In addition, other heavy metals have been associated with gold mining and other metal-dispersing activities in the region. OBJECTIVE Investigate the gut microbiome of two semi-isolated groups from the Amazon, focusing on metal resistance. METHODS Metagenomic data from the Yanomami and Tunapuco gut microbiome were assembled into contigs, and their putative proteins were searched against a database of metal resistance proteins. FINDINGS Proteins associated with mercury resistance were exclusive in the Yanomami, while proteins associated with silver resistance were exclusive in the Tunapuco. Both groups share 77 non-redundant metal resistance (MR) proteins, mostly associated with multi-MR and operons with potential resistance to arsenic, nickel, zinc, copper, copper/silver, and cobalt/nickel. Although both groups harbour operons related to copper resistance, only the Tunapuco group had the pco operon. CONCLUSION The Yanomami and Tunapuco gut microbiome shows that these people have been exposed directly or indirectly to distinct scenarios concerning heavy metals.

Assessing multiple factors affecting the gut microbiome structure of very preterm infants

The composition and diversity of the gut microbiota are essential for the health and development of the immune system of infants. However, there is limited information on factors that influence the gut microbiota of very preterm infants. In this study, we analyzed factors that affect the gut microbiota of very preterm infants. The stool samples from 64 very preterm infants with a gestational age less than 32 weeks were collected for 16S rRNA gene sequencing. The infants were divided according to the delivery mode, antibiotic use during pregnancy, and feeding methods. The abundance of Proteobacteria was high in both cesarean (92.7%) and spontaneous (55.5%) delivery groups and then shifted to Firmicutes after the first week of birth. In addition, Proteobacteria was also the dominant phylum of infant gut microbiome for mothers with antibiotic use, with more than 50% after the first week of birth. In comparison, the dominant phylum for mothers without antibiotic use was Firmicutes. Proteobacteria level was also high in breastfeeding and mixed-feeding groups, consisting of more than 90% of the community. By contrast, Proteobacteria was the dominant phylum at the first week of birth but then shifted to Firmicutes for the formula-fed group. The alterations of gut microbiota in infants can affect their health condition during growth. This study confirmed that the different feeding types, delivery modes, and use of antibiotics during pregnancy can significantly affect the composition of the gut microbiota of very preterm infants.

Structural mechanism of a dual-functional enzyme DgpA/B/C as both a C-glycoside cleaving enzyme and an O- to C-glycoside isomerase

The C-glycosidic bond that connects the sugar moiety with aglycone is difficult to be broken or made due to its inert nature. The knowledge of C-glycoside breakdown and synthesis is very limited. Recently, the enzyme DgpA/B/C cascade from a human intestinal bacterium PUE was identified to specifically cleave the C-glycosidic bond of puerarin (daidzein-8-C-glucoside). Here we investigated how puerarin is recognized and oxidized by DgpA based on crystal structures of DgpA with or without substrate and biochemical characterization. More strikingly, we found that apart from being a C-glycoside cleaving enzyme, DgpA/B/C is capable of efficiently converting O- to C-glycoside showing the activity as a structure isomerase. A possible mechanistic model was proposed dependently of the simulated complex structure of DgpB/C with 3″-oxo-daidzin and structure-based mutagenesis. Our findings not only shed light on understanding the enzyme-mediated C-glycosidic bond breakage and formation, but also may help to facilitate stereospecific C-glycoside synthesis in pharmaceutical industry.

Parkinson's Disease: A Multisystem Disorder / 神经科学通报·英文版

The way sporadic Parkinson's disease (PD) is perceived has undergone drastic changes in recent decades. For a long time, PD was considered a brain disease characterized by motor disturbances; however, the identification of several risk factors and the hypothesis that PD has a gastrointestinal onset have shed additional light. Today, after recognition of prodromal non-motor symptoms and the pathological processes driving their evolution, there is a greater understanding of the involvement of other organ systems. For this reason, PD is increasingly seen as a multiorgan and multisystemic pathology that arises from the interaction of susceptible genetic factors with a challenging environment during aging-related decline.

Isolation of a foodborne Bacillus cereus strain and its effect on intestinal mucosal immunity-associated factors and gut microbial community in mice / 生物工程学报

Bacillus cereus is a common foodborne pathogen. Accidently eating food contaminated by B. cereus will cause vomiting or diarrhea, and even death in severe cases. In the present study, a B. cereus strain was isolated from spoiled rice by streak culture. The pathogenicity and drug resistance of the isolated strain were analyzed by drug sensitivity test and PCR amplification of virulence-associated gene respectively. Cultures of the purified strain were injected intraperitoneally into mice to examine their effects on intestinal immunity-associated factors and gut microbial communities, to provide references for the pathogenic mechanism and medication guidance of these spoilage microorganisms. The results showed that the isolated B. cereus strain was sensitive to norfloxacin, nitrofurantoin, tetracycline, minocycline, ciprofloxacin, spectinomycin, clindamycin, erythrocin, clarithromycin, chloramphenicol, levofloxacin, and vancomycin, but resistant to bactrim, oxacillin and penicillin G. The strain carries seven virulence-associated genes including hblA, hblC, hblD, nheA, nheB, nheC and entFM, which are involved in diarrhea-causing toxins production. After infecting mice, the isolated B. cereus strain was found to cause diarrhea in mice, and the expression levels of immunoglobulins and inflammatory factors in the intestinal mucosae of the challenged mice were significantly up-regulated. Gut microbiome analysis showed that the composition of gut microbial community in mice changed after infection with B. cereus. The abundance of the uncultured_bacterium_f_Muribaculaceae in Bacteroidetes, which is a marker of body health, was significantly decreased. On the other hand, the abundance of uncultured_bacterium_f_Enterobacteriaceae, which is an opportunistic pathogen in Proteobacteria and a marker of dysbacteriosis, was significantly increased and was significantly positively correlated with the concentrations of IgM and IgG. These results showed that the pathogenic B. cereus carrying diarrhea type virulence-associated gene can activate the immune system by altering the composition of gut microbiota upon infection.

Gut dysbiosis, inflammation and type 2 diabetes in mice using synthetic gut microbiota from diabetic humans / Disbiose intestinal, inflamação e diabetes tipo 2 em camundongos usando microbiota intestinal sintética de humanos diabéticos

Abstract The study was aimed to assess impact of high fat diet (HFD) and synthetic human gut microbiota (GM) combined with HFD and chow diet (CD) in inducing type-2 diabetes (T2D) using mice model. To our knowledge, this is the first study using selected human GM transplantation via culture based method coupled dietary modulation in mice for in vivo establishment of inflammation leading to T2D and gut dysbiosis. Twenty bacteria (T2D1-T2D20) from stool samples of confirmed T2D subjects were found to be morphologically different and subjected to purification on different media both aerobically and anerobically, which revealed seven bacteria more common among 20 isolates on the basis of biochemical characterization. On the basis of 16S rRNA gene sequencing, these seven isolates were identified as Bacteroides stercoris (MT152636), Lactobacillus acidophilus (MT152637), Lactobacillus salivarius (MT152638), Ruminococcus bromii (MT152639), Klebsiella aerogenes (MT152640), Bacteroides fragilis (MT152909), Clostridium botulinum (MT152910). The seven isolates were subsequently used as synthetic gut microbiome (GM) for their role in inducing T2D in mice. Inbred strains of albino mice were divided into four groups and were fed with CD, HFD, GM+HFD and GM+CD. Mice receiving HFD and GM+modified diet (CD/HFD) showed highly significant (P<0.05) increase in weight and blood glucose concentration as well as elevated level of inflammatory cytokines (TNF-α, IL-6, and MCP-1) compared to mice receiving CD only. The 16S rRNA gene sequencing of 11 fecal bacteria obtained from three randomly selected animals from each group revealed gut dysbiosis in animals receiving GM. Bacterial strains including Bacteroides gallinarum (MT152630), Ruminococcus bromii (MT152631), Lactobacillus acidophilus (MT152632), Parabacteroides gordonii (MT152633), Prevotella copri (MT152634) and Lactobacillus gasseri (MT152635) were isolated from mice treated with GM+modified diet (HFD/CD) compared to strains Akkermansia muciniphila (MT152625), Bacteriodes sp. (MT152626), Bacteroides faecis (MT152627), Bacteroides vulgatus (MT152628), Lactobacillus plantarum (MT152629) which were isolated from mice receiving CD/HFD. In conclusion, these findings suggest that constitution of GM and diet plays significant role in inflammation leading to onset or/and possibly progression of T2D. .

Resumo O estudo teve como objetivo avaliar o impacto da dieta rica em gordura (HFD) e da microbiota intestinal humana sintética (GM) combinada com HFD e dieta alimentar (CD) na indução de diabetes tipo 2 (T2D) usando modelo de camundongos. Para nosso conhecimento, este é o primeiro estudo usando transplante de GM humano selecionado através do método baseado em cultura acoplada à modulação dietética em camundongos para o estabelecimento in vivo de inflamação que leva a T2D e disbiose intestinal. Vinte bactérias (T2D1-T2D20) de amostras de fezes de indivíduos T2D confirmados verificaram ser morfologicamente diferentes e foram submetidas à purificação em meios diferentes aerobicamente e anaerobicamente, o que revelou sete bactérias mais comuns entre 20 isolados com base na caracterização bioquímica. Com base no sequenciamento do gene 16S rRNA, esses sete isolados foram identificados como Bacteroides stercoris (MT152636), Lactobacillus acidophilus (MT152637), Lactobacillus salivarius (MT152638), Ruminococcus bromii (MT152639), Klebsiella aerogenides (MT152640), Bacteroides fragilis (MT152909), Clostridium botulinum (MT152910). Esses sete isolados foram, posteriormente, usados ​​como microbioma intestinal sintético (GM) por seu papel na indução de T2D em camundongos. Linhagens consanguíneas de camundongos albinos foram divididas em quatro grupos e foram alimentadas com CD, HFD, GM + HFD e GM + CD. Camundongos que receberam a dieta modificada com HFD e GM + (CD / HFD) mostraram um aumento altamente significativo (P < 0,05) no peso e na concentração de glicose no sangue, bem como um nível elevado de citocinas inflamatórias (TNF-α, IL-6 e MCP-1) em comparação com os ratos que receberam apenas CD. O sequenciamento do gene 16S rRNA de 11 bactérias fecais obtidas de três animais selecionados aleatoriamente de cada grupo revelou disbiose intestinal em animais que receberam GM. Cepas bacterianas, incluindo Bacteroides gallinarum (MT152630), Ruminococcus bromii (MT152631), Lactobacillus acidophilus (MT152632), Parabacteroides gordonii (MT152633), Prevotella copri (MT152634) e Lactobacillus Gasseri (MT152635D), foram tratadas com dieta modificada / CD) em comparação com as linhagens Akkermansia muciniphila (MT152625), Bacteriodes sp. (MT152626), Bacteroides faecis (MT152627), Bacteroides vulgatus (MT152628), Lactobacillus plantarum (MT152629), que foram isoladas de camundongos recebendo CD / HFD. Em conclusão, esses resultados sugerem que a constituição de GM e dieta desempenham papel significativo na inflamação levando ao início ou/e possivelmente à progressão de T2D.

Study on the relationship between intestinal flora analysis and CD4 +T lymphocyte subsets in patients with systemic lupus erythematosus / 中华风湿病学杂志

Objective:To explore the characteristics of intestinal microbiota in patients with systemic lupus erythematosus (SLE), and further explore the relationship between microbiota and CD4 +T lymphocyte subsets and disease activity. Methods:Fecal samples were collected from 96 patients with SLE, and 96 sex- and age-matched healthy controls (HCs). The gut microbiota were investigated via 16s rRNA sequencing. Flow cytometry was used to detect peripheral CD4 +T lymphocyte subsets of Th1, Th2, Th17 and Treg cells. Indicators of disease activity such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), complement C3 and C4, Systemic lupus erythematosus disease activity index(SLEDAI) for each patient were recorded. Differential abundance analysis was carried out using the edgeR algorithm. The Wilcoxon rank-sum test was used to compare alpha diversity indices, bacterial abundances, and the F/B ratio between groups. R (version 4.0.1) was used for comparative statistics, and Pearson′s correlation analysis was used to assess the correlations between the relative abundances of bacterial genera and serum levels of ESR, CRP, C3 and C4 in the samples. Results:The alpha estimators of richness (ACE and Chao 1) were significantly reduced in SLE feces samples compared with those of HCs ( P<0.01). Bacterial diversity estimators, including the Shannon ( P<0.01) and Simpson′s ( P<0.01) indices, were also significantly lower in SLE. Significant differences in gut microbiota composition between SLE and HCs were found using the edgeR algorithm. Compared with HC, 24 species of bacteria were significantly different in SLE patients at the genus level ( P<0.05). Moreover, there was a significant positive correlation between CRP and Coprococcus ( r=0.30, P=0.014), C4 and Corynebacterium ( r=0.31, P=0.013) and Faecalibacterium( r=0.25, P=0.048), Hemoglobin and Morganella( r=0.41, P=0.001), as well as SLIDA and Corynebacterium( r=0.25, P=0.047). In terms of lymphocyte subsets, there was significant positive correlation between B cells, Treg cells and Eubacterium eligens group, as well as CD8 +T, CD4 +T, NK cells and Corynebacterium. In additional, Th1 was positively correlated with Shigella Escherichia coli ( r=0.52, P=0.008), and Th2 was positively correlated with Dielma ( r=0.51, P<0.001). Conclusion:The abundance and diversity of intestinal flora in SLE patients were significantly reduced, and the differentially expressed bacteria were closely related to the CD4 +T lymphocyte subsets and disease activity indicators of patients.