Repercussion of inflammatory bowel disease on lung homeostasis: The role of photobiomodulation.

Inflammatory bowel diseases (IBD) are chronic and multifactorial diseases characterized by dysfunction of the intestinal mucosa and impaired immune response. Data show an important relationship between intestine and respiratory tract. The treatments of IBD are limited. Photobiomodulation (PBM) is an effective anti-inflammatory therapy. Our objective was to evaluate the repercussion of IBD as well as its treatment with PBM on pulmonary homeostasis. Male Wistar rats were submitted to IBD induction by acetic acid and treated or not with PBM. Rats were irradiated with red LED on both right and left sides of the ventral surface and beside the external anal region during 3 consecutive days (wavelenght 660 nm, power 100 mw, total energy 15 J and time of irradiation 150 s per point). Our results showed that IBD altered pulmonary homeostasis, since we observed an increase in the histopathological score, in myeloperoxidase activity (MPO), in mast cell degranulation, and in the release and gene expression of cytokines. We also showed that PBM treatment reduced biomarkers of IBD and reverted all augmented parameters in the lung, restoring its homeostasis. Thus, we confirm experimentally the important gut-lung axis and the role of PBM as a promising therapy.

Intravascular laser irradiation of blood (ILIB) used to treat lung diseases: a short critical review.

Intravascular laser irradiation of blood (ILIB) was developed to treat cardiovascular diseases due to its rheological effects. In its original form, ILIB was applied by an intravenous optical fiber, restricting its application. However, this technique was modified to non-invasive irradiation through the radial artery, now called vascular photobiomodulation (VPBM). Many studies have used both, ILIB and VPBM, to treat lung diseases. It is well established that lung diseases affect more than 300 million people worldwide with high morbidity and mortality rates. In this short critical review, we discuss the potential benefits of photobiomodulation to treat lung diseases using these two approaches. The search was performed in the electronic database of MEDLINE (Medical Literature Analysis and Retrieval System Online) via PubMed. The data search was carried out from 1991 to 2017. We selected a total of 10 clinical studies using either ILIB or VPBM, in addition to 2 experimental studies in animals. The respiratory diseases treated in these studies included bronchitis, asthma, pneumonia, and tuberculosis. The results showed overall beneficial effects on lung diseases, characterized by a reduction in the inflammatory cascade and antioxidant effects, improvement of hemodynamic parameters, the efficiency of gas exchange, and reduction of hospitalization periods. In conclusion, all studies showed promising effects of ILIB in both animal and human studies. The studies did not discuss any disadvantages or contraindications. However, further studies are needed in order to understand the dosimetry, and the literature is lacking in randomized, controlled clinical trials. Thus, this review highlights the need for additional studies using this approach.

Comparison between local abdominal and transcutaneous tail vein photobiomodulation in experimental rat model of ulcerative colitis.

Ulcerative colitis (UC) is a chronic autoimmune disease that impacts the quality of life, but current pharmacological treatments are limited. Photobiomodulation (PBM) is a light-based treatment that can be applied either locally or systemically. Here, we compare the effects of local and vascular PBM (VPBM) in an experimental rat model of UC. Male Wistar rats were induced with UC by rectal instillation of acetic acid and treated with either local abdominal PBM or VPBM to the tail vein using a 660-nm LED. The findings indicated that local PBM but not VPBM reduced intestinal histological scores. Both local and VPBM increased mucus production, decreased mast cell degranulation, and modulated TNF-α and IL-1 ß levels in the intestines. Local PBM also affected the expression of the mRNAs for IL-6, TNF-α, and IFN-γ. In conclusion, we suggest that local PBM appears to be more promising than VPBM for treating UC. However, further research is needed to fully understand the mechanisms and to optimize the parameters of PBM for UC treatment.

Effects of photobiomodulation in the experimental acetic acid-induced colitis: comparison between male and female.

Ulcerative colitis (UC) is an important chronic and multifactorial disease, which alters the colon mucosal with a significant impact on life quality affecting both men and women. The difference between genders causes changes in the inflammatory processes, modulating the development of several diseases. The available drugs to treat UC exhibit limited outcomes and side effects; thus, new therapies are needed. Photobiomodulation (PBM) emerges as potential treatment by modulating the inflammatory process without side effects and low costs. The aim of this study was to evaluate the effects of PBM in acetic acid-induced UC comparing the responses between male and females. For this purpose, male and female Wistar rats (36) were submitted to induction of UC by rectal administration of 10% acetic acid (colitis group) and treated or not with PBM (colitis-PBM group) (LED, 660 nm, 100 mW, 150 s) in three points: right side and left of the ventral surface and in the external anal region. Non-manipulated rats were used as control (basal group). We investigated the disease activity index (DAI score), myeloperoxidase enzyme activity (MPO) and release of cytokines in the intestine homogenates, and histological analysis. PBM reduces DAI score, MPO activity, and mast cell degranulation while increased mucous production in both females and males. Moreover, PBM reduced histopathological score as well as the levels of IL-6 and IL-4 in the bowel only in males. We also showed reduced levels of IL-1beta and TNF-alpha after PBM in both males and females, while the levels of IL-10 and IFN-gamma were increased. In conclusion, despite our study has shown some differences between males and females, PBM attenuated the biomarkers of UC in both genders constituting a potential combined treatment that is non-invasive and low cost.

High dose of formaldehyde exposure during pregnancy increases neutrophils lung influx evoked by ovalbumin in the offspring.

OBJECTIVE: Considering that asthma might have their onset in the intrauterine life and the exposure to FA during pregnancy interferes in the immune system of offspring, here we hypothesized that high dose of FA exposure during pregnancy could to contribute for development and severity of asthma in the offspring. METHODS: Pregnant Wistar rats were submitted to FA inhalation (6.13 mg/m(3), 1 h/day, 5 days/week, for 21 days) or vehicle (distillated water). After 30 days of birth, the offspring was sensitized with ovalbumin (OVA)-alum and challenged with aerosolized OVA (1%, 15 min, 3 days). After 24 h the OVA challenge, the analyses were performed. Non-manipulated rats were used as basal parameters. RESULTS: Our data show that the exposure to high dose of FA during pregnancy predisposes the development of neutrophilic lung inflammation in the offspring, as observed by the profile of cells and cytokines in the lung. CONCLUSION: This study contributes to the understanding of effects of pollution on the development of lung diseases.

The brain-gut-microbiota axis in the treatment of neurologic and psychiatric disorders.

The human gut microbiota is a complex ecosystem made of trillions of microorganisms. The composition can be affected by diet, metabolism, age, geography, stress, seasons, temperature, sleep, and medications. The increasing evidence about the existence of a close and bi-directional correlation between the gut microbiota and the brain indicates that intestinal imbalance may play a vital role in the development, function, and disorders of the central nervous system. The mechanisms of interaction between the gut-microbiota on neuronal activity are widely discussed. Several potential pathways are involved with the brain-gut-microbiota axis, including the vagus nerve, endocrine, immune, and biochemical pathways. Gut dysbiosis has been linked to neurological disorders in different ways that involve activation of the hypothalamic-pituitary-adrenal axis, imbalance in neurotransmitter release, systemic inflammation, and increase in the permeability of the intestinal and the blood-brain barrier. Mental and neurological diseases have become more prevalent during the coronavirus disease 2019pandemic and are an essential issue in public health globally. Understanding the importance of diagnosing, preventing, and treating dysbiosis is critical because gut microbial imbalance is a significant risk factor for these disorders. This review summarizes evidence demonstrating the influence of gut dysbiosis on mental and neurological disorders.

A microbiota intestinal humana é um ecossistema complexo feito de trilhões de microrganismos, cuja composição pode ser afetada pela dieta, pelo metabolismo, pela idade, geografia, pelo estresse, pelas estações do ano, pela temperatura, pelo sono e por medicamentos. A crescente evidência sobre a existência de uma correlação estreita e bidirecional entre a microbiota intestinal e o cérebro indica que o desequilíbrio intestinal pode desempenhar um papel vital no desenvolvimento, na função e nos distúrbios do sistema nervoso central. Os mecanismos de interação entre a microbiota intestinal e a atividade neuronal são amplamente discutidos. Várias vias potenciais estão envolvidas com o eixo microbiota-intestino-cérebro, incluindo o nervo vago e as vias endócrinas, imunes e bioquímicas. A disbiose intestinal tem sido associada a distúrbios neurológicos de diferentes maneiras que envolvem a ativação do eixo hipotálamo-hipófise-adrenal, o desequilíbrio na liberação de neurotransmissores, a inflamação sistêmica e o aumento da permeabilidade das barreiras intestinal e hematoencefálica. As doenças mentais e neurológicas tornaram-se mais prevalentes durante a pandemia de coronavirus disease 2019 e são uma questão global essencial na saúde pública. Compreender a importância de diagnosticar, prevenir e tratar a disbiose é fundamental porque o desequilíbrio microbiano intestinal é um fator de risco significativo para esses distúrbios. Esta revisão resume as evidências que demonstram a influência da disbiose intestinal em distúrbios mentais e neurológicos.

Experimental allergic airway inflammation impacts gut homeostasis in mice.

Background: /Aims: Epidemiological data show that there is an important relationship between respiratory and intestinal diseases. To improve our understanding on the interconnectedness between the lung and intestinal mucosa and the overlap between respiratory and intestinal diseases, our aim was to investigate the influence of ovalbumin (OVA)-induced allergic airway inflammation on gut homeostasis. Methods: A/J mice were sensitized and challenged with OVA. The animals were euthanized 24 h after the last challenge, lung inflammation was determined by evaluating cells in Bronchoalveolar lavage fluid, serum anti-OVA IgG titers and colon morphology, inflammation and integrity of the intestinal mucosa were investigated. IL-4 and IL-13 levels and myeloperoxidase activity were determined in the colon samples. The expression of genes involved in inflammation and mucin production at the gut mucosa was also evaluated. Results: OVA challenge resulted not only in lung inflammation but also in macroscopic alterations in the gut such as colon shortening, increased myeloperoxidase activity and loss of integrity in the colonic mucosal. Neutral mucin intensity was lower in the OVA group, which was followed by down-regulation of transcription of ATOH1 and up-regulation of TJP1 and MUC2. In addition, the OVA group had higher levels of IL-13 and IL-4 in the colon. Ova-specific IgG1 and OVA-specific IgG2a titers were higher in the serum of the OVA group than in controls. Conclusions: Our data using the OVA experimental model suggested that challenges in the respiratory system may result not only in allergic airway inflammation but also in the loss of gut homeostasis.

Effects of kefir fermented milk beverage on sodium dextran sulfate (DSS)-induced colitis in rats.

Background and aim: The etiopathogenesis of inflammatory bowel disease (IBD) is associated with different factors such as genetic, infectious, immunological, and environmental, including modification of the gut microbiota. IBD's conventional pharmacological therapeutic approaches have become a challenge due to side effects, complications from prolonged use, and higher costs. Kefir fermented milk beverage is a functional food that has demonstrated multiple beneficial effects including anti-inflammatory and antioxidant activity. Alternative therapeutic strategies have been used for IBD as more natural products with low-cost and easy acquisition. The aim of this study is to evaluate the anti-inflammatory effects of kefir fermented milk beverage on sodium dextran sulfate (DSS)-induced colitis in rats. Methods: We used 4 groups to perform this study: baseline control (BC), kefir control (KC), 5% untreated DSS-induced colitis (DSS), and 5% DSS-induced colitis treated with kefir (DSSK). The animals received fermented kefir milk beverage ad libitum for six days and the disease activity index was recorded daily. Colon samples were processed for Transmission Electron Microscopy and histopathological evaluation. We analyzed short fatty chain acids through the fecal sample using gas chromatography. Results: Kefir supplementation was able to reduce the clinical activity index and inflammatory process evidenced by decreased neutrophil accumulation, decreased reticulum edema, and increased autophagosomes. Also, showed a trend to increase the levels of acetate and propionate. Conclusions: Our results suggest that kefir fermented milk beverage may have an anti-inflammatory effect minimizing the intestinal damage of DSS-induced colitis.

Butyrate: Connecting the gut-lung axis to the management of pulmonary disorders.

Short-chain fatty acids (SCFAs) are metabolites released by bacterial components of the microbiota. These molecules have a wide range of effects in the microbiota itself, but also in host cells in which they are known for contributing to the regulation of cell metabolism, barrier function, and immunological responses. Recent studies indicate that these molecules are important players in the gut-lung axis and highlight the possibility of using strategies that alter their intestinal production to prevent or treat distinct lung inflammatory diseases. Here, we review the effects of the SCFA butyrate and its derivatives in vitro and in vivo on murine models of respiratory disorders, besides discussing the potential therapeutic use of butyrate and the other SCFAs in lung diseases.

Salivary Microbiological and Gingival Health Status Evaluation of Adolescents With Overweight and Obesity: A Cluster Analysis.

Given the high prevalence of obesity in children and adolescents, the investigation of early markers is of clinical importance to better manage this condition. Thus, the aim was to evaluate the cross-sectional relationship between salivary microbiota, gingival health status, and excess weight in adolescents. A total of 248 students (14-17 y; 119 girls) were included, free of caries lesions and periodontal pockets. Physical examination included measures of height, weight, and body fat percentage (%BF). Oral examination was performed to gather information on dental (DMFT index) and gingival health status. Unstimulated saliva was submitted to qPCR reactions to quantify Streptococcus mutans, Porphyromonas gingivalis, Bifidobacteria, and Streptococcus pneumoniae percentages and the NFKappaB expression. Two-way ANOVA was applied considering group (normal-weight/overweight/obesity) and sex factors, in addition to cluster analysis. Group effect was significant for %S. mutans (partial eta2 = 0.20; p < 0.001) and %Bifidobacteria (partial eta2 = 0.19; p < 0.001), with overweight and obesity groups showing the highest levels compared to normal-weight ones, with no significant sex effect. There was no difference in the frequency of gingivitis, P. gingivalis, and S. pneumoniae percentages or NFKappaB expression between groups. Cluster analysis generated three clusters according to body fat accumulation: "Higher %BF," "Moderate %BF," and "Lower %BF." "Higher %BF" cluster was characterized by higher body fat percentage and higher salivary %Bifidobacteria, while cluster "Lower %BF" was characterized by lower body fat percentage and lower frequency of gingivitis ("Moderate %BF" cluster was the contrast). According to nutritional status, a difference in salivary S. mutans and Bifidobacteria percentages was found, with overweight or obesity adolescents showing the highest percentages than normal-weight ones. Besides, a positive relationship between body fat accumulation and Bifidobacteria count was observed, indicating a possible interaction between oral bacteria communities and weight gain.

Use of Gas Chromatography to Quantify Short Chain Fatty Acids in the Serum, Colonic Luminal Content and Feces of mice.

Short-Chain Fatty Acids (SCFAs) are a product of the fermentation of resistant starches and dietary fibers by the gut microbiota. The most important SCFA are acetate (C2), propionate (C3) and butyrate (C4). These metabolites are formed and absorbed in the colon and then transported through the hepatic vein to the liver. SCFAs are more concentrated in the intestinal lumen than in the serum. Butyrate is largely consumed in the gut epithelium, propionate in the liver and acetate in the periphery. SCFAs act on many cells including components of the immune system and epithelial cells by two main mechanisms: activation of G-protein coupled receptors (GPCRs) and inhibition of histone deacetylase. Considering the association between changes in SCFA concentrations and the development of diseases, methods to quantify these acids in different biological samples are important. In this study, we describe a protocol using gas chromatography to quantify SCFAs in the serum, feces and colonic luminal content. Separation of compounds was performed using a DB-23 column (60 m x 0.25 mm internal diameter [i.d.]) coated with a 0.15 µm thick layer of 80.2% 1-methylnaphatalene. This method has a good linear range (15-10,000 µg/ml). The precision (relative standard deviation [RSD]) is less than 15.0% and the accuracy (error relative [ER]) is within ± 15.0%. The extraction efficiency was higher than 97.0%. Therefore, this is cost effective and reproducible method for SCFA measurement in feces and serum.

The brain-gut-microbiota axis in the treatment of neurologic and psychiatric disorders / O eixo microbiota-intestino-cérebro no tratamento de desordens neurológicas e psiquiátricas

Abstract The human gut microbiota is a complex ecosystem made of trillions of microorganisms. The composition can be affected by diet, metabolism, age, geography, stress, seasons, temperature, sleep, and medications. The increasing evidence about the existence of a close and bi-directional correlation between the gut microbiota and the brain indicates that intestinal imbalance may play a vital role in the development, function, and disorders of the central nervous system. The mechanisms of interaction between the gut-microbiota on neuronal activity are widely discussed. Several potential pathways are involved with the brain-gut-microbiota axis, including the vagus nerve, endocrine, immune, and biochemical pathways. Gut dysbiosis has been linked to neurological disorders in different ways that involve activation of the hypothalamic-pituitary-adrenal axis, imbalance in neurotransmitter release, systemic inflammation, and increase in the permeability of the intestinal and the blood-brain barrier. Mental and neurological diseases have become more prevalent during the coronavirus disease 2019pandemic and are an essential issue in public health globally. Understanding the importance of diagnosing, preventing, and treating dysbiosis is critical because gut microbial imbalance is a significant risk factor for these disorders. This review summarizes evidence demonstrating the influence of gut dysbiosis on mental and neurological disorders.

Resumo A microbiota intestinal humana é um ecossistema complexo feito de trilhões de microrganismos, cuja composição pode ser afetada pela dieta, pelo metabolismo, pela idade, geografia, pelo estresse, pelas estações do ano, pela temperatura, pelo sono e por medicamentos. A crescente evidência sobre a existência de uma correlação estreita e bidirecional entre a microbiota intestinal e o cérebro indica que o desequilíbrio intestinal pode desempenhar um papel vital no desenvolvimento, na função e nos distúrbios do sistema nervoso central. Os mecanismos de interação entre a microbiota intestinal e a atividade neuronal são amplamente discutidos. Várias vias potenciais estão envolvidas com o eixo microbiota-intestino-cérebro, incluindo o nervo vago e as vias endócrinas, imunes e bioquímicas. A disbiose intestinal tem sido associada a distúrbios neurológicos de diferentes maneiras que envolvem a ativação do eixo hipotálamo-hipófise-adrenal, o desequilíbrio na liberação de neurotransmissores, a inflamação sistêmica e o aumento da permeabilidade das barreiras intestinal e hematoencefálica. As doenças mentais e neurológicas tornaram-se mais prevalentes durante a pandemia de coronavirus disease 2019 e são uma questão global essencial na saúde pública. Compreender a importância de diagnosticar, prevenir e tratar a disbiose é fundamental porque o desequilíbrio microbiano intestinal é um fator de risco significativo para esses distúrbios. Esta revisão resume as evidências que demonstram a influência da disbiose intestinal em distúrbios mentais e neurológicos.

Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases.

The recently discovered histone post-translational modification crotonylation connects cellular metabolism to gene regulation. Its regulation and tissue-specific functions are poorly understood. We characterize histone crotonylation in intestinal epithelia and find that histone H3 crotonylation at lysine 18 is a surprisingly abundant modification in the small intestine crypt and colon, and is linked to gene regulation. We show that this modification is highly dynamic and regulated during the cell cycle. We identify class I histone deacetylases, HDAC1, HDAC2, and HDAC3, as major executors of histone decrotonylation. We show that known HDAC inhibitors, including the gut microbiota-derived butyrate, affect histone decrotonylation. Consistent with this, we find that depletion of the gut microbiota leads to a global change in histone crotonylation in the colon. Our results suggest that histone crotonylation connects chromatin to the gut microbiota, at least in part, via short-chain fatty acids and HDACs.

New insights into therapeutic strategies for gut microbiota modulation in inflammatory diseases.

The interaction between the gut microbiota and the host immune system is very important for balancing and resolving inflammation. The human microbiota begins to form during childbirth; the complex interaction between bacteria and host cells becomes critical for the formation of a healthy or a disease-promoting microbiota. C-section delivery, formula feeding, a high-sugar diet, a high-fat diet and excess hygiene negatively affect the health of the microbiota. Considering that the majority of the global population has experienced at least one of these factors that can lead to inflammatory disease, it is important to understand strategies to modulate the gut microbiota. In this review, we will discuss new insights into gut microbiota modulation as potential strategies to prevent and treat inflammatory diseases. Owing to the great advances in tools for microbial analysis, therapeutic strategies such as prebiotic, probiotic and postbiotic treatment and fecal microbiota transplantation have gained popularity.

The central role of the gut microbiota in chronic inflammatory diseases.

The commensal microbiota is in constant interaction with the immune system, teaching immune cells to respond to antigens. Studies in mice have demonstrated that manipulation of the intestinal microbiota alters host immune cell homeostasis. Additionally, metagenomic-sequencing analysis has revealed alterations in intestinal microbiota in patients suffering from inflammatory bowel disease, asthma, and obesity. Perturbations in the microbiota composition result in a deficient immune response and impaired tolerance to commensal microorganisms. Due to altered microbiota composition which is associated to some inflammatory diseases, several strategies, such as the administration of probiotics, diet, and antibiotic usage, have been utilized to prevent or ameliorate chronic inflammatory diseases. The purpose of this review is to present and discuss recent evidence showing that the gut microbiota controls immune system function and onset, development, and resolution of some common inflammatory diseases.