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.

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.

Blood orange juice intake changes specific bacteria of gut microbiota associated with cardiometabolic biomarkers.

Blood orange juice is an important source of flavanones and anthocyanins, mainly hesperidin, narirutin, and cyanidin-3-O-glucoside. The benefits of these bioactive compounds have been reported, but the mechanistic details behind their biological effects are not well established. This study investigated the effects of Moro orange (Citrus sinensis L. Osbeck) juice (MOJ) on gut microbiota composition and cardiometabolic biomarkers in overweight women. In this study, 12 overweight women (BMI from 25.0 to 29.9 kg/m2), aged 18-37 years, consumed 500 mL of MOJ every day for 4 weeks. We assessed the gut microbiota composition, levels of short-chain fatty acids (SCFAs), cardiometabolic biomarkers, and insulin resistance (HOMA-IR) at baseline and after 2 weeks and 4 weeks of MOJ intake. The results suggested that MOJ intake affected the abundance of specific operational taxonomic units (OTUs) of the gut microbiota but did not significantly alter the diversity and general composition of the gut microbiota. However, MOJ intake increased the production of SCFAs, especially propionic and isobutyric acids, and significantly improved cardiometabolic biomarkers such as blood pressure and plasma VCAM-1 levels in the overweight women. Additionally, we observed significant associations between gut microbiota OTUs belonging to the Bacteroidetes phyla and Prevotella 9 genera and the cardiometabolic biomarkers. Furthermore, MOJ reduced fasting glucose and insulin levels and HOMA-IR values, thereby enhancing insulin sensitivity in the insulin-resistant overweight women. Finally, we highlighted the importance of orange juice intake duration because some beneficial changes such as blood pressure improvements were evident at the 2-week time interval of the intervention, but other changes became significant only at the 4-week interval of MOJ intake. In conclusion, our study demonstrated that changes in specific OTUs of the gut microbiota in response to MOJ intake were associated with significant improvements in some cardiometabolic biomarkers and SCFA levels in overweight women with insulin resistance.

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.

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.

Women's multisite microbial modulation during pregnancy.

The composition of female microbiome varies with age, physiological and socio-behavior conditions. Also, changes in microbiome composition are observed as pregnancy progresses, especially in the vaginal site. Together with the physiological adaptations of gestation, changes in microbiome composition seem to be fundamental for proper fetal development. This study aimed at simultaneously evaluating the vaginal, gut, and oral microbiome of healthy pregnant women, and comparing it with those observed in healthy non-pregnant women of reproductive age. In a cross-sectional study, vaginal, oral and gut samples were collected from 42 pregnant and 18 non-pregnant women, and the microbiome composition was evaluated by 16S rRNA sequencing, using Illumina platform. In the pregnant group, we observed a positive correlation between Eubacterium and Akkermansia in the gut samples; between Eubacterium and Ruminococcus in the vaginal samples; and between Streptococcus and Gemella in the oral samples. Notwithstanding, we observed a negative correlation between Lactobacillus and Atopobium and between Lactobacillus and Gardnerella in vaginal microbiome. Prevotella was the only genus found in all three sites studied; however, there was no signal of bacterial influence between sites during pregnancy. These results suggest that in addition to hormonal and immunological variations during healthy pregnancy, the female body also undergoes microbiome modulation in multiple sites in order to maintain an eubiotic status.

Gut Microbiome of Children and Adolescents With Primary Sclerosing Cholangitis in Association With Ulcerative Colitis.

Few studies reported the relation of intestinal microbiome composition and diversity in pediatric patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC). In this cross-sectional study, we selected patients younger than 19 years old from the pediatric gastroenterology and hepatology outpatient clinic of a tertiary hospital to describe the intestinal microbiome of pediatric patients with PSC associated or not to UC. Patients were divided in PSC, PSC+UC, and UC diagnosis. A stool sample was collected from each patient (n=30) and from a healthy relative/neighbor (n=23). The microbiome composition was assessed using MiSeq (Illumina) platform. Differences in microbial composition were found between PSC and PSC+UC groups. The relative abundance of Veillonella and Megasphaera genera were increased depending on patients' age at diagnosis. Veillonella was also increased in patients who were in an active status of the disease. Both genera were positively correlated to total bilirubin and gamma-glutamyl transferase. As a conclusion, the disease, the age and the disease activity status seem to influence the intestinal microbiome, highlighting the difference of intestinal microbiome profile for patients depending on age at diagnosis. We also showed an increase of Veillonella in patients with PSC and PSC+UC, and a positive correlation of dysbiosis and higher gamma-glutamyl transferase and total bilirubin in PSC+UC patients. Our findings are promising in the diagnosis, prognosis, and future therapeutic perspectives for PSC patients.

The Human Milk Microbiota is Modulated by Maternal Diet.

Human milk microorganisms contribute not only to the healthy development of the immune system in infants, but also in shaping the gut microbiota. We evaluated the effect of the maternal diet during pregnancy and during the first month of lactation on the human milk microbiota in a cross-sectional study including 94 healthy lactating women. Microbiota composition was determined by 16S rDNA profiling and nutrient intake assessed through food questionnaires. Thirteen genera were present in at least 90% of all samples, with three genera present in all samples: Streptococcus, Staphylococcus, and Corynebacterium. Cluster analysis indicated two distinct compositions: one marked by a high abundance of Streptococcus (cluster 1), and other by a high abundance of Staphylococcus (cluster 2). A global association with milk microbiota diversity was observed for vitamin C intake during pregnancy (p = 0.029), which was higher for cluster 2 individuals (cluster 2 median = 232 mg/d; cluster 1 = 175 mg/d; p = 0.02). Positive correlations were found between Bifidobacterium in the milk and intake of polyunsaturated and linoleic fatty acids during the lactation period (p < 0.01). We show that maternal diet influences the human milk microbiota, especially during pregnancy, which may contribute in shaping the gut microbiota.

Microbiome and its relation to gestational diabetes.

PURPOSE: Gestational diabetes mellitus (GDM), the major endocrine pathology in pregnancy, has been associated with the development of an intense inflammatory process and increased insulin resistance. The maternal microbiota is involved in several metabolic functions; however, its role in GDM physiopathology remains unclear. The aim of this study was to assess the composition of the microbiota at different sites and evaluate its relationship with the occurrence of GDM. METHODS: This cross-sectional study recruited women in the third trimester of gestation with and without GDM. Oral, vaginal, and stool samples were evaluated using next-generation sequencing. We included 68 participants: 26 with and 42 without GDM. RESULTS: The analysis of the oral microbiome did not show significant differences in phyla and genus among the studied groups. In contrast, GDM patients presented a specific vaginal and intestinal microbiome composition, which was less diverse than those found in the control group, showing genera related to dysbiosis. CONCLUSIONS: Our findings suggest that changes in the composition of the vaginal and intestinal microbiome might be involved in the development of GDM. The follow-up of these patients in order to evaluate vaginal and intestinal samples after delivery may contribute to understanding the development of metabolic disease in women with previous GDM.

Shifts in intestinal microbiota after duodenal exclusion favor glycemic control and weight loss: a randomized controlled trial.

BACKGROUND: In recent years, studies indicate gut microbiota as an important modulator in the pathophysiology of type 2 diabetes. Environmental and genetic factors interact to control the host's intestinal microbiota, triggering metabolic disorders such as obesity and insulin resistance. OBJECTIVES: The objective of this study was to identify the fecal microbiota in adult type 2 diabetes patients and to assess changes in composition after metabolic surgery. SETTING: University Hospital of the University of São Paulo. METHODS: Twenty-one patients were enrolled in a randomized controlled study divided into 2 arms. One group underwent duodenal-jejunal bypass surgery with minimal gastric resection, and fecal samples were collected before the operation and after 6 and 12 months. The other group received medical care (standard care group) and was followed for 12 months. Fecal samples were collected at baseline and after 6 and 12 months. Fecal microbiota was analyzed using high-throughput sequencing with V4 16 S rRNA primers. RESULTS: The fecal microbiota in duodenal-jejunal bypass surgery with minimal gastric resection group (Bacteroides, Akkermansia, and Dialister) exhibited increased abundance and diversity compared with that in the standard care group; however, the increase in A. muciniphila was only statistically significant in the surgical group, probably due to the study's small sample size. CONCLUSIONS: The data presented suggest that duodenal-jejunal bypass surgery with minimal gastric resection increases microbial richness and abundancy, mainly for those bacteria related to weight loss and metabolic control (Akkermansia), providing a better understanding of the role of microbiota in type 2 diabetes regulation and its changes after metabolic surgery.

Microbiome in normal and pathological pregnancies: A literature overview.

This review summarizes recent findings on the changes that occur during pregnancy in the composition of the vaginal and gut microbiome and their association with metabolic, hormonal, and immunological factors. Despite many studies on the topic, the vaginal and gut microbial profiles and their influence on the course of pregnancy are still unclear. We present data suggesting that, contrary to traditional understanding, the placenta is not sterile but has a microbial community. We review and discuss new findings on changes in the richness and diversity of the microbiota of pregnant women with term or preterm births, obesity, and gestational diabetes mellitus. Several factors influence the bacterial profile of these women and may explain, at least in part, some of the discrepant findings between studies. The development of and access to new molecular biology methods and techniques has expanded the possibilities of research. This will contribute to a better understanding of the microbiome and its role in normal and pathological pregnancies.