Unveiling contrasts in microbiota response: A1c control improves dysbiosis in low-A1c T2DM, but fails in high-A1c cases-a key to metabolic memory?

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is associated with dysbiosis in the gut microbiota (MB). Individually, each medication appears to partially correct this. However, there are no studies on the response of the MB to changes in A1c. Therefore, we investigated the MB's response to intensive glycemic control. RESEARCH DESIGN AND METHODS: We studied two groups of patients with uncontrolled T2DM, one group with an A1c <9% (18 patients-G1) and another group with an A1c >9% (13 patients-G2), aiming for at least a 1% reduction in A1c. We collected A1c and fecal samples at baseline, 6, and 12 months. G1 achieved an average A1c reduction of 1.1%, while G2 a reduction of 3.13%. RESULTS: G1's microbiota saw a decrease in Erysipelotrichaceae_UCG_003 and in Mollicutes order (both linked to metabolic syndrome and associated comorbidities). G2, despite having a more significant reduction in A1c, experienced an increase in the proinflammatory bacteria Megasphaera and Acidaminococcus, and only one beneficial genus, Phascolarctobacterium, increased, producer of butyrate. CONCLUSION: Despite a notable A1c outcome, G2 could not restore its MB. This seeming resistance to change, leading to a persistent inflammation component found in G2, might be part of the "metabolic memory" in T2DM.

Chronic consumption of orange juice modifies urinary excretion of flavanone gut-derived metabolites through gut microbiota modulation.

The metabolism and absorption of citrus flavanones are intrinsically linked to the gut microbiota, creating a bidirectional relationship where these compounds influence the microbiome, and in turn, the microbiota affects their metabolism. This study evaluates the effect of acute and chronic consumption of orange juice (OJ) on the urinary excretion of gut-derived flavanone metabolites and the gut microbiota. Health volunteers ingested 500 mL of OJ for 60 days in a single-arm human intervention study. Blood and feces were collected at baseline and after 60 days, with an additional 24-hour urine collection after a single dose on day 1 and day 63. LC-MS/MS analyzed urinary flavanone metabolites, while 16S rRNA sequencing characterized gut microbiota. Total urinary hesperetin conjugates excretion significantly decreased over 60 days, while gut-derived total phenolic acids, particularly three hydroxybenzoic acids, increased. Moreover, the heterogeneity of the total amount of flavanone conjugates, initially categorizing individuals into high-, medium- and low- urinary excretor profiles, shifted towards medium-excretor, except for five individuals who remained as low-excretors. This alteration was accompanied by a decrease in intestinal ß-glucosidase activity and a shift in the relative abundance of specific genera, such as decreases in Blautia, Eubacterium hallii, Anaerostipes, and Fusicatenibacter, among which, Blautia was associated with higher urinary flavanone conjugates excretion. Conversely, an increase in Prevotella was observed. In summary, chronic OJ consumption induced transient changes in gut microbiota and altered the metabolism of citrus flavanones, leading to distinct urinary excretion profiles of flavanone metabolites.

Establishment of oral microbiome in very low birth weight infants during the first weeks of life and the impact of oral diet implementation.

Very low birth weight (VLBW) infants, mostly preterm, have many barriers to feeding directly from the mother's breast, and need to be fed alternatively. Feeding is a major influencer in oral microbial colonization, and this colonization in early life is crucial for the promotion of human health. Therefore, this research aimed to observe the establishment of oral microbiome in VLBW infants during their first month of life through hospitalization, and to verify the impact caused by the implementation of oral diet on the colonization of these newborns. We included 23 newborns followed during hospitalization and analyzed saliva samples collected weekly, using 16S rRNA gene sequencing. We observed a significant decrease in richness and diversity and an increase in dominance over time (q-value < 0.05). The oral microbiome is highly dynamic during the first weeks of life, and beta diversity suggests a microbial succession in early life. The introduction of oral diet does not change the community structure, but affects the abundance, especially of Streptococcus. Our results indicate that although time is related to significant changes in the oral microbial profile, oral feeding benefits genera that will remain colonizers throughout the host's life.

Fecal microbiota transplantation in patients with metabolic syndrome and obesity: A randomized controlled trial.

BACKGROUND: Metabolic syndrome is a multifactorial disease, and the gut microbiota may play a role in its pathogenesis. Obesity, especially abdominal obesity, is associated with insulin resistance, often increasing the risk of type two diabetes mellitus, vascular endothelial dysfunction, an abnormal lipid profile, hypertension, and vascular inflammation, all of which promote the development of atherosclerotic cardiovascular disease. AIM: To evaluate the outcomes of fecal microbiota transplantation (FMT) in patients with metabolic syndrome. METHODS: This was a randomized, single-blind placebo-controlled trial comparing FMT and a sham procedure in patients with metabolic syndrome. We selected 32 female patients, who were divided into eight groups of four patients each. All of the patients were submitted to upper gastrointestinal endoscopy. In each group, two patients were randomly allocated to undergo FMT, and the other two patients received saline infusion. The patients were followed for one year after the procedures, during which time anthropometric, bioimpedance, and biochemical data were collected. The patients also had periodic consultations with a nutritionist and an endocrinologist. The primary end point was a change in the gut microbiota. RESULTS: There was evidence of a postprocedural change in microbiota composition in the patients who underwent FMT in relation to that observed in those who underwent the sham procedure. However, we found no difference between the two groups in terms of the clinical parameters evaluated. CONCLUSION: There were no significant differences in biochemical or anthropometric parameters, between the two groups evaluated. Nevertheless, there were significant postprocedural differences in the microbiota composition between the placebo group. To date, clinical outcomes related to FMT remain uncertain.

The gut microbiome of obese postpartum women with and without previous gestational diabetes mellitus and the gut microbiota of their babies.

BACKGROUND: The incidence of gestational diabetes mellitus (GDM) is increasing worldwide, and has been associated with some changes in the gut microbiota. Studies have shown that the maternal gut microbiota pattern with hyperglycemia can be transmitted to the offspring. The study aimed to evaluate the gut microbiota of obese postpartum women with and without previous GDM and their offspring. METHODS: We evaluated a total of 84 puerperal women who had (n = 40) or not GDM (n = 44), and their infants were also included. Stool samples were obtained 2-6 months after delivery. The molecular profile of the fecal microbiota was obtained by sequencing V4 region of 16S rRNA gene (Illumina® MiSeq). RESULTS: We found that the gut microbiota structures of the puerperal women and their infants were similar. Stratifying according to the type of delivery, the relative abundance of Victivallis genus was higher in women who had natural delivery. Exposure to exclusive breastfeeding was associated with a greater abundance of Bacteroides and Staphylococcus. The differential abundance test showed correlations to clinical and laboratory parameters. This work showed no difference in the microbiota of obese puerperal women with and without GDM and their offspring. However, breastfeeding contributed to the ecological succession of the intestinal microbiota of the offspring. CONCLUSION: This work can contribute to understanding the potential effects of GDM and early life events on the gut microbiome of mothers and their offspring and its possible role in metabolism later in life.

Gut Microbiota across Normal Gestation and Gestational Diabetes Mellitus: A Cohort Analysis.

The prevalence of gestational diabetes mellitus (GDM) is a global public health concern. The mechanism that leads to glucose tolerance beyond normal physiological levels to pathogenic conditions remains incompletely understood, and it is speculated that the maternal microbiome may play an important role. This study analyzes the gut microbiota composition in each trimester of weight-matched women with and without GDM and examines possible bacterial genera associations with GDM. This study followed 56 pregnant women with GDM and 59 without admitted to the outpatient clinic during their first/second or third trimester of gestation. They were submitted to a standardized questionnaire, dietary recalls, clinical examination, biological sample collection, and molecular profiling of fecal microbiota. Women with GDM were older and had a higher number of pregnancies than normal-tolerant ones. There was no difference in alpha diversity, and the groups did not differ regarding the overall microbiota structure. A higher abundance of Bacteroides in the GDM group was found. A positive correlation between Christensenellaceae and Intestinobacter abundances with one-hour post-challenge plasma glucose and a negative correlation between Enterococcus and two-hour plasma glucose levels were observed. Bifidobacterium and Peptococcus abundances were increased in the third gestational trimester for both groups. The gut microbiota composition was not dependent on the presence of GDM weight-matched women throughout gestation. However, some genera abundances showed associations with glucose metabolism. Our findings may therefore encourage a deeper understanding of physiological and pathophysiological changes in the microbiota throughout pregnancy, which could have further implications for diseases prevention.

Saccharomyces boulardii exerts renoprotection by modulating oxidative stress, renin angiotensin system and uropathogenic microbiota in a murine model of diabetes.

AIMS: We aimed to investigate whether Saccharomyces boulardii strain might exert renoprotective effects by modulating renal renin angiotensin system, oxidative stress and intestinal microbiota in streptozotocin-diabetic mice. MAIN METHODS: Thirty-six C57BL/6 male mice were divided into four groups: control (C), control + probiotic (CP), diabetes (D), diabetes + probiotic (DP). Diabetes was induced by one intraperitoneal injection of streptozotocin and Saccharomyces boulardii was administered by oral gavage for 8 weeks. Blood glucose, albuminuria and urinary volume were measured. Renal levels of angiotensin peptides (angiotensin I, II and 1-7) and the activities of angiotensin-converting enzyme (ACE) and ACE2 were determined, besides that, renal morphology, serotonin and dopamine levels and also microbiota composition were analyzed. KEY FINDINGS: Probiotics significantly increased C-peptide secretion and reduced blood glucose of diabetic animals. Saccharomyces boulardii also improved renal antioxidant defense, restored serotonin and dopamine concentration, and activated the renin-angiotensin system (RAS) vasodilator and antifibrotic axis. The modulation of these markers was associated with a beneficial impact on glomerular structure and renal function of diabetic treated animals. The phenotypic changes induced by Saccharomyces boulardii were also related to modulation of intestinal microbiota, evidenced by the decreased abundance of Proteus and Escherichia-Shigella, considered diabetic nephropathy biomarkers. SIGNIFICANCE: Therefore, probiotic administration to streptozotocin-induced diabetic mice improves kidney structure and function in a murine model and might represent a reasonable strategy to counteract nephropathy-associated maladaptive responses in diabetes.

Impact of Oropharyngeal Administration of Colostrum in Preterm Newborns' Oral Microbiome.

The initial colonization of the human microbiota is of paramount importance. In this context, the oropharyngeal administration of colostrum is a safe, viable, and well-tolerated practice even by the smallest preterm infants. Therefore, this study evaluated the effects of oropharyngeal administration of colostrum on the establishment of preterm infants' oral microbiota. A longitudinal observational study was carried out with 20 premature neonates, divided into two groups: one receiving the protocol (Oropharyngeal Administration of Colostrum; OAC) and the other one receiving Standard Caare (SC). Saliva samples were collected from the newborns weekly during the study period (from the day of birth until the 21st day of life) for analysis of oral microbiota through 16S rRNA gene sequencing. We observed that the colonization of the oral microbiota of preterm newborns preseanted a higher relative abundance of Staphylococcus on the 7th day of life, mainly in the OAC group. Additionally, an increased abundance of Bifidobacterium and Bacteroides was observed in the OAC group at the first week of life. Regarding alpha and beta diversity, time was a key factor in the oral modulation of both groups, showing how dynamic this environment is in early life.

Caracterização da microbiota vaginal, intestinal e oral durante o período gestacional / Vaginal, gut and oral microbiota characterization during pregnancy

A simbiose desenvolvida entre seres vivos e microrganismos desempenha um importante papel na relação saúde-doença do hospedeiro. Neste sentido, o corpo humano abriga uma grande e diversa comunidade de microrganismos, sendo as mucosas vaginal, intestinal e oral as principais superfícies mucosas do corpo feminino que abrigam as comunidades bacterianas de fundamental importância para a mulher. Estes microrganismos atuam no desenvolvimento e modulação do sistema imune, na manutenção e otimização de vias metabólicas e competem por sítios de colonização, prevenindo que microrganismos patogênicos estabeleçam colonização. A composição da microbiota feminina varia com a idade, pH, secreção hormonal, ciclo menstrual, uso de anticoncepcional e atividade sexual. O presente estudo buscou caracterizar a composição da microbiota do corpo feminino durante o período gestacional, comparando os achados entre gestantes e não gestantes saudáveis, através de técnicas de biologia molecular. Foram selecionadas 60 mulheres saudáveis para o estudo e coletadas amostras de secreção vaginal, fezes e swab oral de cada participante. O DNA das amostras foi extraído e submetido à sequenciamento do gene 16S rRNA e quantificado através da técnica de PCR em tempo real. Das participantes selecionadas, 42 eram gestantes e 18 eram mulheres não gestantes em idade reprodutiva. Observamos que a quantificação total de bactérias na vagina não apresentou diferenças entre gestantes e não gestantes. Houve aumento na abundância de Lactobacillus no sítio vaginal, bactérias produtoras de butirato na microbiota intestinal e Streptococcus na microbiota oral de mulheres grávidas quando comparadas com mulheres não gestantes. Além disso, observamos que a composição e a disposição dos gêneros encontrados sofrem uma modificação, tal como aumento de gêneros relacionados com a manutenção da homeostase no grupo de mulheres gestantes. O período gestacional influencia positivamente na composição da microbiota, garantindo assim a prevalência de gêneros bacterianos responsáveis pela manutenção das condições ideais para o desenvolvimento da gestação saudável

The symbiosis developed between living organisms and microorganisms plays an important role in the health-disease relationship of the host. In this sense, the human body harbor a large and diverse community of microorganisms, the vaginal, intestinal and oral mucosa are the main mucosal surfaces of the female body that harbor bacterial communities of fundamental importance for women. These microorganisms act in the development and modulation of the immune system, in the maintenance and optimization of metabolic pathways and compete for colonization sites, preventing pathogenic microorganisms from establishing colonization. The composition of the female microbiota varies with age, pH, hormonal secretion, menstrual cycle, contraceptive use and sexual activity. The present study aimed to characterize the microbiota composition of the female body during the gestational period, comparing the findings between healthy and non - pregnant women through molecular biology techniques. Sixty healthy women were selected for the study and samples of vaginal secretion, stool and oral swab from each participant were collected. The DNA of the samples was extracted and submitted to the 16S rRNA gene sequencing and quantified by the real-time PCR technique. Were select, 42 were pregnant and 18 were non-pregnant women of reproductive age. We observed that the total quantification of bacteria in the vaginal samples did not present differences between pregnant and non-pregnant women. There was an increase in the abundance of Lactobacillus in the vaginal site, butyrate producing bacteria in the intestinal microbiota and Streptococcus in the oral microbiota of pregnant women when compared to nonpregnant women. In addition, we observed that the composition and arrangement of the genera found undergo a modification, such as an increase in genera related to the maintenance of homeostasis in the group of pregnant women. The pregnancy influences the composition of the microbiota, thus ensuring the prevalence of bacterial genera responsible for the maintenance of the ideal conditions for the development of healthy pregnancy