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Dynamics of gut microbiota during pregnancy in women with TPOAb-positive subclinical hypothyroidism: a prospective cohort study.
Wu, M, Chi, C, Yang, Y, Guo, S, Li, T, Gu, M, Zhang, T, Gao, H, Liu, R, Yin, C
BMC pregnancy and childbirth. 2022;22(1):592
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Subclinical hypothyroidism (SCH) in pregnancy refers to the elevation of thyroid stimulating hormone level with normal free T4 level. One third of women with SCH have been reported to test positive for anti-thyroid peroxidase antibody (TPOAb+). The aim of this study was to evaluate whether gut microbiota can be potential therapeutic targets for managing TPOAb+ SCH. This study was a nested, prospective observational cohort study. A total of 64 and 68 pregnant women with TPOAb+ and TPOAb negative SCH, respectively, were included in this study. Results showed that women who were diagnosed with TPOAb+ SCH in trimester (T)1 show distinct dynamics of gut microbiota from T2 to T3. Furthermore, changes in the abundances of three types of bacterial species were abnormal in the presence of levothyroxine treatment. Authors conclude that gut microbiota can serve as potential therapeutic targets for TPOAb+ SCH during pregnancy.
Abstract
BACKGROUND Anti-thyroid peroxidase antibody (TPOAb) positivity can contribute to inhibit thyroxine synthesis. Gut microbiota can interact with metabolic or immune diseases. However, dynamics of gut microbiota from the second (T2) to the third trimester (T3) in women with TPOAb-positive/negative subclinical hypothyroidism (TPOAb+/TPOAb- SCH) have not been reported. Therefore, we aimed to evaluate whether gut microbiota can be potential therapeutic targets for managing TPOAb+ SCH. METHODS In this single-center prospective cohort study, we observed gut microbiota dynamics by sequencing 16S rRNA from fecal samples collected in T2 (20-23+ 6 weeks) and T3 (28-33+ 6 weeks). TPOAb+/TPOAb- SCH were stratified depending on whether or not they used levothyroxine (LT4) during the pregnancy (LT4+/LT4-). Microbiome bioinformatics analyses were performed using QIIME2. The linear discriminant analysis effect size (LEfSe) was used for the quantitative analysis of biomarkers. Functional profiling was performed with PICRUSt2. RESULTS Distinct gut microbiota dynamics from T2 to T3 were noted in the TPOAb- (n = 68) and TPOAb+ (n = 64) SCH groups. The TPOAb+ LT4- group was characterized by enriched bacterial amplicon sequence variants (ASVs) of Prevotella in T2 and Bacteria, Lachnospirales, Lachnospiraceae, Blautia, and Agathobacter in T3 and by depleted ASVs of Gammaproteobacteria, Enterobacterales, and Enterobacteriaceae in T2 and Actinobacteriota, Coriobacteriia, Actinobacteria, Coriobacteriales, Bifidobacteriales, Bifidobacteriaceae, Bifidobacterium, Dorea formicigenerans, and Bifidobacterium longum in T3. The TPOAb+ LT4+ group was characterized by enriched bacterial ASVs of Blautia, Streptococcus salivarius, and Bifidobacterium longum in T3 and by depleted ASVs of Bacteroidota, Bacteroidia, Bacteroidales, and Prevotella in T2 and Agathobacter in T3. Moreover, we identified 53 kinds of metabolic functions that were mainly involved in sugar, lipid, and amino acid metabolism. CONCLUSIONS Our results indicated that low dynamics of gut microbiota composition and high dynamics of its metabolic function from T2 to T3 were associated with TPOAb+ SCH. We concluded that gut microbiota could be new targets for treatment of TPOAb+ SCH during pregnancy. TRIAL REGISTRATION This study was retrospectively registered at the Chinese Clinical Trial Registry (registration number ChiCTR2100047175 ) on June 10, 2021.
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Maternal allergen-specific IgG might protect the child against allergic sensitization.
Lupinek, C, Hochwallner, H, Johansson, C, Mie, A, Rigler, E, Scheynius, A, Alm, J, Valenta, R
The Journal of allergy and clinical immunology. 2019;144(2):536-548
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Analysis of allergen-specific IgE responses in birth cohorts with allergens has provided detailed information regarding the development of specific IgE responses in children. Data regarding early development of allergen-specific IgG is needed. The aim of this study is to investigate whether maternal allergen-specific IgG can protect against IgE sensitization in their children. Plasma samples were taken from mothers during the third trimester, cord blood, breast milk collected 2 months after delivery; and from children at 6, 12, and 60 months of age. These samples were analysed for IgG reactivity to 164 allergens in 99 families. IgE sensitizations to allergens were determined at 5 years of age in the children. Children who were IgE sensitized against an allergen at 5 years of age had significantly higher allergen-specific IgG levels than non-sensitised children. For all 164 tested allergens, children from mothers with higher levels of specific plasma IgG levels against an allergen had no IgE sensitizations against that allergen at 5 years of age. High levels of allergen-specific IgG in mothers during the third trimester and in cord blood seem to protect against allergic sensitization in offspring. This finding has implications for allergy prevention.
Abstract
BACKGROUND Analysis of allergen-specific IgE responses in birth cohorts with microarrayed allergens has provided detailed information regarding the evolution of specific IgE responses in children. High-resolution data regarding early development of allergen-specific IgG are needed. OBJECTIVE We sought to analyze IgG reactivity to microarrayed allergens in mothers during pregnancy, in cord blood samples, in breast milk, and in infants in the first years of life with the aim to investigate whether maternal allergen-specific IgG can protect against IgE sensitization in the offspring. METHODS Plasma samples from mothers during the third trimester, cord blood, breast milk collected 2 months after delivery, and plasma samples from children at 6, 12, and 60 months of age were analyzed for IgG reactivity to 164 microarrayed allergens (ImmunoCAP ISAC technology) in 99 families of the Swedish birth cohort Assessment of Lifestyle and Allergic Disease During Infancy (ALADDIN). IgE sensitizations to microarrayed allergens were determined at 5 years of age in the children. RESULTS Allergen-specific IgG reactivity profiles in mothers, cord blood, and breast milk were highly correlated. Maternal allergen-specific IgG persisted in some children at 6 months. Children's allergen-specific IgG production occurred at 6 months and reflected allergen exposure. Children who were IgE sensitized against an allergen at 5 years of age had significantly higher allergen-specific IgG levels than nonsensitized children. For all 164 tested allergens, children from mothers with increased (>30 ISAC standardized units) specific plasma IgG levels against an allergen had no IgE sensitizations against that allergen at 5 years of age. CONCLUSION This is the first detailed analysis of the molecular IgG recognition profile in mothers and their children in early life. High allergen-specific IgG reactivity in the mother's plasma and breast milk and in cord blood seemed to protect against allergic sensitization at 5 years of age.
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SunGold Kiwifruit Supplementation of Individuals with Prediabetes Alters Gut Microbiota and Improves Vitamin C Status, Anthropometric and Clinical Markers.
Wilson, R, Willis, J, Gearry, RB, Hughes, A, Lawley, B, Skidmore, P, Frampton, C, Fleming, E, Anderson, A, Jones, L, et al
Nutrients. 2018;10(7)
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Increased plasma glucose levels are linked with increased oxidative stress. An increase in the uptake of antioxidants such as vitamin C through diet has been demonstrated by several studies as contributing to the maintenance of normal glucose levels and reducing the risk factors for Type 2 diabetes. The aim of this study was to investigate the vitamin C status, anthropometric measurements and faecal microbiota of an individual on consumption of high vitamin C kiwi fruit for a period of 12 weeks. Baseline measures were compared at the end of 12 weeks resulting in significant increase in plasma vitamin C status (14 µmol/L, p < 0.001). Significant reduction in blood pressure measurement (4 mmHg, p = 0.029), reduction in waist- to- hip ratio and waist- circumference, decrease in blood glucose marker HbA1c (1 mmol/mol, p = 0.005) and increase in fasting glucose (0.1 mmol/L, p = 0.046) were also observed at the end of twelve weeks. Faecal microbiota composition showed an increase in the abundance of uncharacterised bacterial family. The authors concluded that these result were not sufficiently significant to draw conclusions and further studies with larger sample sizes are required to confirm the outcomes of this study.
Abstract
Kiwifruit are a nutrient dense food and an excellent source of vitamin C. Supplementation of the diet with kiwifruit enhances plasma vitamin C status and epidemiological studies have shown an association between vitamin C status and reduced insulin resistance and improved blood glucose control. In vitro experiments suggest that eating kiwifruit might induce changes to microbiota composition and function; however, human studies to confirm these findings are lacking. The aim of this study was to investigate the effect of consuming two SunGold kiwifruit per day over 12 weeks on vitamin C status, clinical and anthropometric measures and faecal microbiota composition in people with prediabetes. This pilot intervention trial compared baseline measurements with those following the intervention. Participants completed a physical activity questionnaire and a three-day estimated food diary at baseline and on completion of the trial. Venous blood samples were collected at each study visit (baseline, 6, 12 weeks) for determination of glycaemic indices, plasma vitamin C concentrations, hormones, lipid profiles and high-sensitivity C-reactive protein. Participants provided a faecal sample at each study visit. DNA was extracted from the faecal samples and a region of the 16S ribosomal RNA gene was amplified and sequenced to determine faecal microbiota composition. When week 12 measures were compared to baseline, results showed a significant increase in plasma vitamin C (14 µmol/L, p < 0.001). There was a significant reduction in both diastolic (4 mmHg, p = 0.029) and systolic (6 mmHg, p = 0.003) blood pressure and a significant reduction in waist circumference (3.1 cm, p = 0.001) and waist-to-hip ratio (0.01, p = 0.032). Results also showed a decrease in HbA1c (1 mmol/mol, p = 0.005) and an increase in fasting glucose (0.1 mmol/L, p = 0.046), however, these changes were small and were not clinically significant. Analysis of faecal microbiota composition showed an increase in the relative abundance of as yet uncultivated and therefore uncharacterised members of the bacterial family Coriobacteriaceae. Novel bacteriological investigations of Coriobacteriaceae are required to explain their functional relationship to kiwifruit polysaccharides and polyphenols.
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Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study.
Kang, DW, Adams, JB, Gregory, AC, Borody, T, Chittick, L, Fasano, A, Khoruts, A, Geis, E, Maldonado, J, McDonough-Means, S, et al
Microbiome. 2017;5(1):10
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Children with autism spectrum disorders (ASD) often suffer gastrointestinal problems, such as constipation or diarrhea, the severity of which often correlate with ASD severity. This open-label clinical trial evaluated the impact of Microbiota Transfer Therapy (MTT) on GI and ASD symptoms of 18 ASD-diagnosed children. Treatment involved 2 weeks of antibiotic treatment and a bowel cleanse, followed by extended fecal microbiota transplant using a high initial dose and lower maintenance doses for 7-8 weeks. Results showed significant improvements in GI symptoms, which persisted 8 weeks after treatment ended. Bacterial diversity also increased. Behavioural ASD symptoms also improved significantly and lasted 8 weeks after treatment finished. This exploratory study suggests a promising approach to alter the gut microbiome in ASD subjects, improving GI and behavioural symptoms of ASD. Further clinical research is required.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Fecal Microbiota Transfer Therapy demonstrates an effective clinical intervention in pediatric patients suffering with autistic spectrum disorder and associated gastrointestinal symptoms.
- Benefits of the therapy in this trail persisted even 2 months after treatment cessation.
- Future research on autistic spectrum disorder should address microbiota-gut-brain axis.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
The article describes an original clinical protocol in which microbiota transfer was used to ameliorate gastrointestinal (GI) and autism symptoms in pediatric patients. Common occurrence of GI pathology in patients affected by autistic spectrum disorder (ASD), poses a clinical challenge, since there is no standardised specific therapy. In light of recent insights on the importance of microbiota-gut-brain axis in health and disease, microbiota emerges as a salient treatment target in the aforementioned population.
Clinical practice applications:
Fecal microbiota transfer therapy (MTT) applied by the protocol described in the article demonstrates a longer-term effective clinical intervention in pediatric patients suffering from ASD and concomitant GI symptoms. Benefits of the therapy persisted even two months after actual treatment cessation, a highly important feature considering ASD.
Considerations for future research:
This modality could complement current treatments used for ASD-related symptomatology, but requires further validation through additional clinical experiments. The procedure also supports the efforts to focus more research on the role of microbiota in ASD pathophysiology. Further basic and clinical investigations on ASD should include addressing microbiota-gut-brain axis whenever possible, if not always.
Abstract
BACKGROUND Autism spectrum disorders (ASD) are complex neurobiological disorders that impair social interactions and communication and lead to restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. The causes of these disorders remain poorly understood, but gut microbiota, the 1013 bacteria in the human intestines, have been implicated because children with ASD often suffer gastrointestinal (GI) problems that correlate with ASD severity. Several previous studies have reported abnormal gut bacteria in children with ASD. The gut microbiome-ASD connection has been tested in a mouse model of ASD, where the microbiome was mechanistically linked to abnormal metabolites and behavior. Similarly, a study of children with ASD found that oral non-absorbable antibiotic treatment improved GI and ASD symptoms, albeit temporarily. Here, a small open-label clinical trial evaluated the impact of Microbiota Transfer Therapy (MTT) on gut microbiota composition and GI and ASD symptoms of 18 ASD-diagnosed children. RESULTS MTT involved a 2-week antibiotic treatment, a bowel cleanse, and then an extended fecal microbiota transplant (FMT) using a high initial dose followed by daily and lower maintenance doses for 7-8 weeks. The Gastrointestinal Symptom Rating Scale revealed an approximately 80% reduction of GI symptoms at the end of treatment, including significant improvements in symptoms of constipation, diarrhea, indigestion, and abdominal pain. Improvements persisted 8 weeks after treatment. Similarly, clinical assessments showed that behavioral ASD symptoms improved significantly and remained improved 8 weeks after treatment ended. Bacterial and phagedeep sequencing analyses revealed successful partial engraftment of donor microbiota and beneficial changes in the gut environment. Specifically, overall bacterial diversity and the abundance of Bifidobacterium, Prevotella, and Desulfovibrio among other taxa increased following MTT, and these changes persisted after treatment stopped (followed for 8 weeks). CONCLUSIONS This exploratory, extended-duration treatment protocol thus appears to be a promising approach to alter the gut microbiome and virome and improve GI and behavioral symptoms of ASD. Improvements in GI symptoms, ASD symptoms, and the microbiome all persisted for at least 8 weeks after treatment ended, suggesting a long-term impact. TRIAL REGISTRATION This trial was registered on the ClinicalTrials.gov, with the registration number NCT02504554.
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Antioxidant supplementation and nasal inflammatory responses among young asthmatics exposed to high levels of ozone.
Sienra-Monge, JJ, Ramirez-Aguilar, M, Moreno-Macias, H, Reyes-Ruiz, NI, Del Río-Navarro, BE, Ruiz-Navarro, MX, Hatch, G, Crissman, K, Slade, R, Devlin, RB, et al
Clinical and experimental immunology. 2004;138(2):317-22
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Exposure to air pollution has been related to an increased occurrence and severity of asthma. In this double-blind, randomised trial, a group of asthmatic children in Mexico City were given either a daily supplement containing 250mg of vitamin C and 50mg of vitamin E, or a placebo pill, for 12 weeks. Scientists measured inflammatory markers in the nasal passages of the children after being exposed to air pollution. Children who received the vitamin supplement did not experience an increase in inflammation after being exposed to air pollution, whereas children given the placebo did. The authors concluded that supplementation with antioxidants such as vitamin C and vitamin E might decrease nasal inflammation in children with asthma who are exposed to air pollution.
Abstract
The inflammatory response to ozone in atopic asthma suggests that soluble mediators of inflammation are released in response to oxidant stress. Antioxidants may alleviate additional oxidative stress associated with photochemical oxidant pollution. This study investigates the impact of antioxidant supplementation on the nasal inflammatory response to ozone exposure in atopic asthmatic children. We conducted a randomized trial using a double-blinded design. Children with asthma (n = 117), residents of Mexico City, were given randomly a daily supplement of vitamins (50 mg/day of vitamin E and 250 mg/day of vitamin C) or placebo. Nasal lavages were performed three times during the 4-month follow-up and analysed for content of interleukin-6 (IL-6), IL-8, uric acid and glutathione (GSx). IL-6 levels in the nasal lavage were increased significantly in the placebo group after ozone exposure while no increase was observed in the supplement group. The difference in response to ozone exposure between the two groups was significant (P = 0.02). Results were similar for IL-8, but with no significant difference between the groups (P = 0.12). GSx decreased significantly in both groups. Uric acid decreased slightly in the placebo group. Our data suggest that vitamin C and E supplementation above the minimum dietary requirement in asthmatic children with a low intake of vitamin E might provide some protection against the nasal acute inflammatory response to ozone.