Lactobacillus rhamnosus Modulates Lung Inflammation and Mitigates Gut Dysbiosis in a Murine Model of Asthma-COPD Overlap Syndrome.

The asthma-COPD overlap syndrome (ACOS) presents lung inflammation similar to both asthma and chronic obstructive pulmonary disease (COPD). Due to the immune response between the lung and gut, it is possible that ACOS individuals present gut dysbiosis. Due to therapeutic limitations in ACOS, Lactobacillus rhamnosus (Lr) have received attention once Lr has been effective in asthma and COPD. However, there is no data about the Lr effect on both lung inflammation and gut dysbiosis in ACOS. Thus, our study investigated the Lr effect on lung inflammation, bronchoconstriction, airway remodeling, and gut dysbiosis in the murine ACOS model. Treated mice with Lr were exposed to HDM and cigarette smoke to induce ACOS. Sixty days after ACOS induction, mice were euthanized. Lung inflammation was evaluated in leukocytes in bronchoalveolar lavage fluid (BALF), airway remodeling, cytokine secretion, and transcription factor expression in the lung. The gut microbiota was assayed by 16S mRNA sequencing from a fecal sample. Leukocyte population, bronchial hyperreactivity, pro-inflammatory cytokines, and airway remodeling were attenuated in Lr-treated ACOS mice. Likewise, IL-4, IL-5, and IL-13, STAT6 and GATA3, as well as IL-17, IL-21, IL-22, STAT3, and RORÉ£t were reduced after Lr. In addition, IL-2, IL-12, IFN-γ, STAT1, and T-bet as well as IL-10, TGF-ß, STAT5, and Foxp3 were restored after the Lr. Firmicutes was reduced, while Deferribacteres was increased after Lr. Likewise, Lr decreased Staphylococcus and increased Mucispirillum in ACOS mice. Lr improves fecal bacterial ß-diversity. Our findings show for the first time the Lr effect on lung inflammation and gut dysbiosis in murine ACOS.

Composição da microbiota intestinal durante a gestação e puerpério em mulheres com diferentes intensidades de sintomas depressivos / Composition of Gut Microbiota During Pregnancy and Postpartum in Women with Varying Degrees of Depressive Symptoms

Os sintomas depressivos durante a gravidez e o período pós-parto (PP) são prevalentes e podem ter implicações profundas para o bem-estar materno e infantil. Evidências emergentes sugerem que a microbiota intestinal pode desempenhar um papel na regulação do humor. Este estudo explora a relação entre a composição da microbiota intestinal e os sintomas depressivos em mulheres grávidas e no pós-parto com diferentes intensidade de sintomas. Foram recrutadas gestantes que faziam acompanhamento nos hospitais HCFMUSP e HU- USP. A partir do preenchimento do questionário de Escala de Edimburgo as participantes foram triadas para os grupos de sintomas ausentes ou leves (AL) e sintomas graves ou moderados (MG). Para a análise de microbiota, as participantes forneceram amostras de fezes em três momentos diferentes. Uma no terceiro trimestre de gestação (G) e duas no período pós-parto. A primeira amostra deste período foi coletada durante a internação do pós-parto (P1), e a segunda durante a consulta de retorno um mês após o parto (P2). A composição da microbiota intestinal foi analisada usando técnicas de sequenciamento de alto rendimento e os ácidos graxos de cadeia curta (AGCC) foram quantificados por cromatografia gasosa acoplada à espectrometria de massas (GC-MS). Análises bioinformáticas e estatísticas foram realizadas utilizando os softwares QIIME 2 (2022.2) e R (4.3.1) para identificar possíveis associações entre a composição da microbiota intestinal e a gravidade dos sintomas depressivos. Os resultados indicam que a familia Enterobacteriacea aparece com maior abundância nas mulheres do grupo MG, especialmente durante o período P1 (p<0,05) e que há uma diminuição significativa (p<0,05) de sintomas depressivos nas participantes do grupo MG desde sua triagem até o fim do acompanhamento do estudo, indicando que conduta terapêutica está sendo eficaz. Apesar de não ter sido estabelecida diferença estatística na abundância relativa da microbiota entre os grupos durante a gestação e nos índices de alfa e beta diversidade entre grupos e entre os períodos, é possivel observar uma tendência de mudança de microbiota ao longo do tratamento com aumento do gênero Bifidobacterium, diminuição da familia Enterobacteraceae e é possivel observar uma aparente correlação inversa entre a diminuição da intensidade de sintomas depressivos e o aumento da abundância dos gêneros Bifidobacterium e Clostridium, além do aumento das concentrações de AGCC. Em conclusão, a composição da microbiota intestinal parece ser influenciada pela gravidade dos sintomas depressivos em mulheres grávidas e no pós-parto. Pesquisas adicionais são necessárias para explorar a relação entre a microbiota intestinal e a depressão perinatal e determinar as implicações clínicas dessas descobertas para a saúde materna e infantil.

Depressive symptoms during pregnancy and the postpartum period (PP) are prevalent and can have profound implications for maternal and infant well-being. Emerging evidence suggests that the gut microbiota may play a role in mood regulation. This study explores the relationship between gut microbiota composition and depressive symptoms in pregnant and postpartum women with different symptom severities. A cohort of pregnant women were recruited from HCFMUSP and HU-USP. Participants completed standardized depression assessment tools and were allocate in groups of absent or mild depressive symptoms (AL) and moderate or severe depressive symptoms (MG) and provided stool samples in three different time periods. One at the third gestation trimester (G) and two at the postpartum period. The first sample from this period was collected during postpartum hospitalization(P1), and the second during the onemonth postpartum follow-up appointment (P2). Their gut microbiota composition was analyzed using high-throughput sequencing techniques and Gas chromatography mass spectrometry (GS-MS) for quantification of short-chain fatty acids (SCFAs). Bioinformatic and statistical analyses were performed using softwares QIIME 2 (2022.2) and R (4.3.1) to identify potential associations between gut microbiota composition and depressive symptom severity. Findings that the Enterobacteriaceae family appears more abundantly in women of the MG group, especially during period P1 (p<0.05), and that there is a significant decrease (p<0.05) in depressive symptoms among the participants of the MG group from their screening to the end of the study follow-up, suggesting that the therapeutic approach is effective. Although no statistical differences in alpha and beta diversity indices were established between groups and across periods, it is possible to observe a trend of microbiota change during the treatment, with an increase in the Bifidobacterium genus, a decrease in the Enterobacteriaceae family, and an apparent inverse correlation between the reduction in the intensity of depressive symptoms and the increased abundance of the Bifidobacterium, Clostridium, and Dorea genera, as well as an increase in the concentrations of SCFAs. In conclusion, composition of gut microbiota appears to be influenced by the severity of depressive symptoms in pregnant and postpartum women. Further research is warranted to explore links between gut microbiota and perinatal depression and to determine the clinical implications of these findings for maternal and infant health