Dysbiosis and leaky gut in hyper-inflated COPD patients: Have smoking and exercise training any role?

BACKGROUND: To characterize the leaky gut syndrome in a cohort of COPD patients with lung hyperinflation according to their clinical history (i.e. hyperinflation severity, chronic respiratory failure [CRF] presence, GOLD stage, prescribed therapy, smoking history) and with or without recent exercise training activity. METHODS: At the ambulatory visit, we evaluated selected COPD patients with lung hyperinflation [residual volume (RV)≥110% pred, TLC≤120% pred)] in clinical stability, identifying them as those who have attended a recent program of exercise training and those who were waiting for it. Clinical and respiratory characteristics (forced expiratory volume at the first second, forced vital capacity, and arterial blood gasses) were collected. Microbiota composition (CFU/ml), and intestinal permeability (i.e., Zonulin ng/ml) were measured in the stool and normalized to the normality cutoff value. RESULTS: All patients [n = 32, median age: 67 years, median RV: 185.0% pred (IQR: 162.0-206.0) and TLC 125.0% pred (IQR: 113.0-138.0)] showed depletion of Lactobacilli, Bacteroides and a great increase in E. Coli, KES (2 and 6.4 times) and Saccharomyces concentrations (2.5 times) other than normality. All evaluations on gut microbiota composition in the whole population were independent of BMI, CRF, GOLD stage or hyperinflation severity, and inhaled steroid therapy. Smoking habits (smokers vs ex-smokers) influenced only Bacteroides species (p<0.05) and no systemic inflammation was present in these patients. On the contrary, Zonulin concentration, a marker of intestinal permeability, was significantly higher than normal (2.8 times) and was correlated with Saccharomyces (p = 0.013). Zonulin (p = 0.001) and Saccharomyces (p<0.0001) were also significantly different in patients undergoing exercise training with respect to those on the waiting list for training. These findings were not influenced by smoking habits. CONCLUSIONS: A marked dysbiosis and leaky gut alteration characterize all COPD hyper-inflated patients, being worse in patients waiting for exercise training. A pre-to-post study is necessary to confirm these preliminary findings.

Characterization of Gut Microbiota Composition in Type 2 Diabetes Patients: A Population-Based Study.

(1) Background: A clinical laboratory index to assess gut dysbiosis is the F/B ratio < 0.8. In fact, an elevated proportion of Firmicutes and a reduced population of Bacteroides in diabetes type 2 (T2D) subjects has been observed. This study aimed to detail the dysbiosis status in the Italian population, focusing on some pathogenic spectra (T2D) or metabolic disorders. (2) Material and methods: A quantity of 334 fecal samples was analyzed in order to perform genetic testing and sequencing. (3) Results: A trend in over imbalance was observed in the percentage of Proteobacteria (median value: 6.75%; interquartile range (IQR): 3.57−17.29%). A statistically significant association (χ2p = 0.033) was observed between type of dysbiosis and T2D, corresponding to an Odds Ratio (OR) of 1.86. It was noted that females with cystitis/candidiasis are significantly prevalent in T2D patients (p < 0.01; OR: 3.59; 95% CI: 1.43−8.99). Although, in non-diabetic males, a sugar craving is significantly associated with the rate of dysbiosis in non-diabetic males (p < 0.05; OR 1.07; 95% CI 1.00−1.16). (4) Conclusion: In T2D patients, the Bacteroidetes/Firmicutes ratio was biased in favor of Proteobacteria, to be expected due to the nutritional habits of the patients. Thus, T2D females had altered gut permeability favoring the development of infections in the vaginal tract.

Impact of Gut Dysbiosis on the Risk of Non-Small-Cell Lung Cancer.

Background: The imbalance of gut microbiota, dysbiosis, is associated with various malignant diseases. This study aimed to identify the characteristics of gut microbiota in age-matched treatment-naïve non-small-cell lung cancer (NSCLC) patients and healthy individuals to investigate possible gut-microbe-related pathways involved in the development of NSCLC. Methods: We enrolled 34 age-matched NSCLC patients and 268 healthy individuals. Hypervariable V3−V4 amplicons of 16S rRNA in freshly collected fecal samples were sequenced. Diversity, microbial composition, functional pathways, smoking history, and gut-microbe-related comorbidities were analyzed to assess the factors associated with the risk of NSCLC. Results: Microbial alpha diversity was decreased in the patients with NSCLC, and beta diversity was significantly different between the patients and controls (p < 0.001). After adjustments for sex, smoking history, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, and 11 abundant microbes with significant differences between the patients and controls, the enrichment of Anaerotruncus spp. and Bacteroides caccae was associated with an increased risk of NSCLC (p = 0.003 and 0.007, respectively). The areas under receiver operating characteristic curves were 71.4% and 66.9% for Anaerotruncus spp. and Bacteroides caccae, respectively (both p < 0.001). Furthermore, the abundance of Bacteroides caccae was positively correlated with steroid hormone biosynthesis (p < 0.001), N-glycan biosynthesis (p = 0.023), glycosaminoglycan degradation (p < 0.001), lipoic acid metabolism (p = 0.039), peroxisome (p < 0.001), and apoptosis (p < 0.001), but inversely related to glycerolipid metabolism (p < 0.001). Anaerotruncus spp. was positively associated with decreased biosynthesis of ansamycin only (p = 0.001). No overlapping signaling pathways were modulated by Bacteroides caccae or Anaerotruncus spp. Conclusions: Our results revealed that fecal Anaerotruncus spp. and Bacteroides caccae were abundant and may be associated with the risk of NSCLC regardless of sex, smoking history, and gut-microbe-related comorbidities. Further investigations on the mechanism underlying the potential association between gut dysbiosis and the development of NSCLC are warranted.

A New Comorbidity in Periodontitis: Fusobacterium nucleatum and Colorectal Cancer.

There is very recent and strong evidence relating Fusobacterium nucleatum to colorectal cancer. In this narrative review, we update the knowledge about gingival dysbiosis and the characteristics of Fusobacterium nucleatum as one of the main bacteria related to periodontitis. We provide data on microbiome, epidemiology, risk factors, prognosis, and treatment of colorectal cancer, one of the most frequent tumours diagnosed and whose incidence increases every year. We describe, from its recent origin, the relationship between this bacterium and this type of cancer and the knowledge and emerging mechanisms that scientific evidence reveals in an updated way. A diagram provided synthesizes the pathogenic mechanisms of this relationship in a comprehensive manner. Finally, the main questions and further research perspectives are presented.

Association Between Gut Microbiota and Autoimmune Thyroid Disease: A Systematic Review and Meta-Analysis.

Background: Autoimmune thyroid disease (AITD) is characterized by thyroid dysfunction and deficits in the autoimmune system. Growing attention has been paid toward the field of gut microbiota over the last few decades. Several recent studies have found that gut microbiota composition in patients with AITD has altered, but no studies have conducted systematic reviews on the association between gut microbiota and ATID. Methods: We searched PubMed, Web of Science, Embase, and Cochrane databases without language restrictions and conducted a systematic review and meta-analysis of eight studies, including 196 patients with AITD. Results: The meta-analysis showed that the alpha diversity and abundance of certain gut microbiota were changed in patients with AITD compared to the controls. Chao1,the index of the microflora richness, was increased in the Hashimoto's thyroiditis group compared to controls (SMD, 0.68, 95%CI: 0.16 to 1.20), while it was decreased in the Graves' disease group (SMD, -0.87, 95%CI: -1.46 to -0.28). In addition, we found that some beneficial bacteria like Bifidobacterium and Lactobacillus were decreased in the AITD group, and harmful microbiota like Bacteroides fragilis was significantly increased compared with the controls. Furthermore, the percentage of relevant abundance of other commensal bacteria such as Bacteroidetes, Bacteroides, and Lachnospiraceae was increased compared with the controls. Conclusions: This meta-analysis indicates an association between AITD and alteration of microbiota composition at the family, genus, and species levels. Systematic Review Registration: PROSPERO, identifier CRD42021251557.

Association of Adherent-invasive Escherichia coli with severe Gut Mucosal dysbiosis in Hong Kong Chinese population with Crohn's disease.

Adherent invasive Escherichia Coli (AIEC) has been implicated in the pathogenesis of Crohn's disease (CD) in Western populations. Whether the presence of AIEC is also seen in CD populations of different genetic susceptibility and has negative impact on host microbiota ecology and therapeutics are unclear. AIEC presence was assessed in ileal tissues of 60 Hong Kong Chinese patients with CD and 56 healthy subjects. Mucosa microbiota was analyzed by 16s rRNA sequencing. Impact of AIEC on the gut microbiota was determined in a mouse model. AIEC was significantly more prevalent in ileal tissues of patients with CD than controls (30% vs 7.1%). Presence of AIEC in ileal tissues was associated with more severe mucosa microbiota dysbiosis in CD with decreased diversity and lower abundance of Firmicutes including butyrate producing Roseburia and probiotic Bacillus. A random forest model predicted the presence of AIEC with area under the curve of 0.89. AIEC exacerbated dysbiosis in dextran sodium sulfate (DSS)-induced colitis mice and led to resistance to restoration of normal gut microbiota by fecal microbiota transplantation (FMT). Proportion of donor-derived bacteria in AIEC-colonized mice was significantly lower than that in uninfected mice. AIEC was prevalent and associated with severe mucosa microbiota dysbiosis in CD in Hong Kong Chinese population. The presence of AIEC impeded restoration of normal gut microbiota. AIEC may serve as a keystone bacterium in CD and impact the efficacy of FMT.

The Impact of Highly Effective CFTR Modulators on Growth and Nutrition Status.

Patients with cystic fibrosis (CF) are at increased risk of malnutrition and growth failure due to multiple factors as a result of suboptimal or absent function of the CFTR chloride channel protein. Dysfunctional CFTR contributes to increased energy expenditure, exocrine pancreatic insufficiency causing impaired dietary macronutrient digestion and absorption, intestinal dysbiosis, and impaired bile acid homeostasis. Poor nutritional status as a result of these mechanisms is associated with decreased lung function, worse clinical outcomes, and ultimately, increased mortality. Nutritional interventions addressing these mechanisms, such as pancreatic enzyme-replacement therapy and enteral caloric supplementation, have improved nutritional status and, by association, clinical outcomes. In the last decade, the advent of medications targeting defective CFTR proteins has revolutionized the care of patients with CF by reducing the overall impact of CFTR dysfunction. Below, we summarize the effects of highly effective CFTR modulators on nutritional status overall as well as specific factors including bile acid metabolism, pancreatic function, energy expenditure, and intestinal dysbiosis. The future of CF nutrition care will require a paradigm shift away from focusing on methods addressing CFTR dysfunction such as excess calorie provision and toward an individualized, holistic approach in the context of specific mutations and CFTR-directed therapy.

The prevalence of intestinal dysbiosis in patients referred for antireflux surgery.

BACKGROUND: Prior to antireflux surgery, most patients with symptoms of gastroesophageal reflux disease (GERD) have been taking long-term proton pump inhibitors (PPIs). PPIs have been shown to cause changes to the intestinal microbiota, such as small intestinal bacterial overgrowth (SIBO), which is characterised by symptoms of gas bloating. Patients undergoing antireflux surgery are not routinely screened for SIBO, yet many patients experience gas-related symptoms postoperatively. METHODS: Data from consecutive patients (n = 104) referred to a speciality reflux centre were retrospectively assessed. Patients underwent a routine diagnostic workup for GERD including history, endoscopy, oesophageal manometry and 24-h pH-impedance monitoring off PPIs. Intestinal dysbiosis was determined by hydrogen and methane breath testing with a hydrogen-positive result indicative of SIBO and a methane-positive result indicative of intestinal methanogen overgrowth (IMO). RESULTS: 60.6% of patients had intestinal dysbiosis (39.4% had SIBO and 35.6% had IMO). Patients with dysbiosis were more likely to report bloating (74.6% vs 48.8%; P = 0.01) and belching (60.3% vs 34.1%; P = 0.01). The oesophageal acid exposure time and number of reflux episodes were similar between dysbiosis and non-dysbiosis groups, but patients with dysbiosis were more likely to have a positive reflux-symptom association (76.2% vs 31.7%; P < 0.001), especially for regurgitation in those with SIBO (P = 0.01). Hydrogen gas production was significantly greater in patients with a positive reflux-symptom association for regurgitation (228.8 ppm vs 129.1 ppm, P = 0.004) and belching (mean AUC 214.8 ppm vs 135.9 ppm, P = 0.02). CONCLUSIONS: The prevalence of intestinal dysbiosis is high in patients with GERD, and these patients are more likely to report gas-related symptoms prior to antireflux surgery. Independently, SIBO may be a contributory factor to refractory reflux symptoms and gas bloating in antireflux surgery candidates.

An association between chronic widespread pain and the gut microbiome.

OBJECTIVES: Chronic widespread musculoskeletal pain (CWP) is a characteristic symptom of fibromyalgia, which has been shown to be associated with an altered gut microbiome. Microbiome studies to date have not examined the milder CWP phenotype specifically nor have they explored the role of raised BMI. The aim of this study was to investigate whether the microbiome is abnormal in CWP. METHODS: CWP was assessed using a standardized screening questionnaire in female volunteers from the TwinsUK cohort including 113 CWP cases and 1623 controls. The stool microbiome was characterized using 16S rRNA amplicon sequencing and amplicon sequence variants, and associations with CWP examined using linear mixed-effects models adjusting for BMI, age, diet, family relatedness and technical factors. RESULTS: Alpha diversity was significantly lower in CWP cases than controls (Mann-Whitney test, P-values 2.3e-04 and 1.2e-02, for Shannon and Simpson indices respectively). The species Coprococcus comes was significantly depleted in CWP cases (Padj = 3.04e-03). A genome-wide association study (GWAS) performed for C. comes in TwinsUK followed by meta-analysis with three Dutch cohorts (total n = 3521) resulted in nine suggestive regions, with the most convincing on chromosome 4 near the TRAM1L1 gene (rs76957229, P = 7.4e-8). A Mendelian randomization study based on the results of the GWAS did not support a causal role for C. comes on the development of CWP. CONCLUSIONS: We have demonstrated reduced diversity in the microbiome in CWP, indicating an involvement of the gut microbiota in CWP; prospectively the microbiome may offer therapeutic opportunities for this condition.

Serum Gastrin Predicts Hydrogen-Producing Small Intestinal Bacterial Overgrowth in Patients With Abdominal Surgery: A Prospective Study.

OBJECTIVES: Small intestinal bacterial overgrowth (SIBO) might be associated with a history of abdominal surgery. We aimed to evaluate the prevalence of SIBO and to investigate serum gastrin and pepsinogen as predictors of SIBO in patients with a history of hysterectomy, gastrectomy, or cholecystectomy. METHODS: This prospective study surveyed 146 patients with a history of hysterectomy, gastrectomy, or cholecystectomy, and 30 healthy controls, who underwent a hydrogen (H2)-methane (CH4) glucose breath test (GBT) for SIBO. Serum pepsinogen I and II and gastrin levels were reviewed. RESULTS: GBT positivity (+) was significantly higher in patients with histories of abdominal surgery than that in in controls (37.6% vs 13.3%, P < 0.01). Among GBT+ patients, 36.0% (18/50), 96.2% (25/26), and 17.1% (12/70) were in the hysterectomy, gastrectomy, and cholecystectomy groups, respectively. Among the GBT subtypes, 43.6% (24/55), 10.9% (6/55), and 45.5% (25/55) of patients were in the GBT(H2)+, GBT(CH4)+, and GBT(mixed)+ groups, respectively. The gastrectomy group had significantly more GBT+ or GBT(H2)+ patients than the other surgical groups. Gastrin levels were higher in GBT(H2)+ patients and lower in GBT(CH4)+ patients than those in GBT- patients. Previous gastrectomy and elevated gastrin levels were independent predictive factors of GBT(H2)+. DISCUSSION: SIBO is not uncommon in patients with histories of abdominal surgeries, but it is more common in patients who have undergone gastrectomy. Serum gastrin level could be a serologic predictor of H2-producing SIBO. The relationship between serum gastrin and SIBO requires further research.

Effects of both Pro- and Synbiotics in Liver Surgery and Transplantation with Special Focus on the Gut-Liver Axis-A Systematic Review and Meta-Analysis.

The gut-liver axis is of upmost importance for the development of infections after surgery. Further bacterial translocation due to surgery-related dysbiosis is associated with limited detoxification function of the liver compromising outcome of surgical therapy. After liver surgery, about 30% of patients develop a bacterial infection, with the risk of bacteremia or even sepsis-associated liver failure and mortality in >40%. The potential benefit of pro-/synbiotics given before surgery is still under debate. Thus, a systematic literature search on trials comparing patients with or without supplementation and outcome after liver resection or transplantation was performed. Our search strategy revealed 12 relevant studies on perioperative administration of pro-/synbiotics in liver surgery. The pro-/synbiotic combinations and concentrations as well as administration timeframes differed between studies. Five studies were performed in liver transplantation and 7 in liver resection. All studies but one reported lower infection rates (pooled RR: 0.46, 95% CI: 0.31-0.67) with pro-/synbiotics. Liver function was assessed after LT/LR in 3 and 5 studies, respectively. Pro-/synbiotics improved function in 1/3 and 2/5 studies, respectively. Concluding, perioperative pro-/synbiotics clearly reduce infection after liver surgery. However, standard protocols with both well-defined probiotic strain preparations and administration timeframes are pending.

Gastric Microbiota in a Low-Helicobacter pylori Prevalence General Population and Their Associations With Gastric Lesions.

INTRODUCTION: Non-Helicobacter pylori microbiota might account for some cases with unexplained chronic gastritis that may in a minority eventually progress to gastric cancer through the Correa cascade. We characterized gastric microbiota by describing the normal stomach, compared it with early precancerous lesions and other disease states, and assessed whether H. pylori status affects bacterial diversity. METHODS: In a population-based study of those with and without gastrointestinal symptoms, cytology brush samples were collected during endoscopy from 316 individuals. Mucosal status was classified as normal mucosa (171), nonatrophic H. pylori gastritis (33), atrophic gastritis (12), or antral chemical gastritis (61). The 16S rRNA gene sequencing and analysis were performed to characterize the microbiota. RESULTS: Microbiota in atrophic gastritis and nonatrophic H. pylori gastritis stomachs were dysbiotic and differed from those in the normal stomach (P = 0.001). The normal stomach had the highest microbial diversity, followed by antral chemical gastritis. The atrophic gastritis and chronic H. pylori gastritis groups had the lowest diversity, a difference that was statistically significant (P = 0.01). Besides H. pylori, non-H. pylori bacteria accounted for group differences. Microbial network analysis showed that the normal group network was most highly connected, whereas the H. pylori gastritis group had the lowest connection. We found an increasing positive co-occurrence of oral bacteria in the stomach because samples deviated from the normal network, some of which were pathogens. The H. pylori-negative group had the highest microbial diversity (Shannon index) compared with the H. pylori-positive group (P = 0.001). DISCUSSION: In this low-H. pylori prevalence general population, the gastric mucosal microbiota of the normal stomach differed significantly from those with nonatrophic or atrophic gastritis. There was an increasing abundance of pathogenic bacteria from the normal state to early precancerous states.

Microbiota and Lifestyle: A Special Focus on Diet.

It is widely known that a good balance and healthy function for bacteria groups in the colon are necessary to maintain homeostasis and preserve health. However, the lack of consensus on what defines a healthy gut microbiota and the multitude of factors that influence human gut microbiota composition complicate the development of appropriate dietary recommendations for our gut microbiota. Furthermore, the varied response to the intake of probiotics and prebiotics observed in healthy adults suggests the existence of potential inter- and intra-individual factors, which might account for gut microbiota changes to a greater extent than diet. The changing dietary habits worldwide involving consumption of processed foods containing artificial ingredients, such as sweeteners; the coincident rise in emotional disorders; and the worsening of other lifestyle habits, such as smoking habits, drug consumption, and sleep, can together contribute to gut dysbiosis and health impairment, as well as the development of chronic diseases. This review summarizes the current literature on the effects of specific dietary ingredients (probiotics, prebiotics, alcohol, refined sugars and sweeteners, fats) in the gut microbiota of healthy adults and the potential inter- and intra-individual factors involved, as well as the influence of other potential lifestyle factors that are dramatically increasing nowadays.

Thyroid-Gut-Axis: How Does the Microbiota Influence Thyroid Function?

A healthy gut microbiota not only has beneficial effects on the activity of the immune system, but also on thyroid function. Thyroid and intestinal diseases prevalently coexist-Hashimoto's thyroiditis (HT) and Graves' disease (GD) are the most common autoimmune thyroid diseases (AITD) and often co-occur with Celiac Disease (CD) and Non-celiac wheat sensitivity (NCWS). This can be explained by the damaged intestinal barrier and the following increase of intestinal permeability, allowing antigens to pass more easily and activate the immune system or cross-react with extraintestinal tissues, respectively. Dysbiosis has not only been found in AITDs, but has also been reported in thyroid carcinoma, in which an increased number of carcinogenic and inflammatory bacterial strains were observed. Additionally, the composition of the gut microbiota has an influence on the availability of essential micronutrients for the thyroid gland. Iodine, iron, and copper are crucial for thyroid hormone synthesis, selenium and zinc are needed for converting T4 to T3, and vitamin D assists in regulating the immune response. Those micronutrients are often found to be deficient in AITDs, resulting in malfunctioning of the thyroid. Bariatric surgery can lead to an inadequate absorption of these nutrients and further implicates changes in thyroid stimulating hormone (TSH) and T3 levels. Supplementation of probiotics showed beneficial effects on thyroid hormones and thyroid function in general. A literature research was performed to examine the interplay between gut microbiota and thyroid disorders that should be considered when treating patients suffering from thyroid diseases. Multifactorial therapeutic and preventive management strategies could be established and more specifically adjusted to patients, depending on their gut bacteria composition. Future well-powered human studies are warranted to evaluate the impact of alterations in gut microbiota on thyroid function and diseases.

Is periodontal disease a risk factor for severe COVID-19 illness?

Periodontal disease (PD) comprises a group of diseases involving inflammatory aspects of the host and dysbiotic events that affect periodontal tissues and could have systemic implications. Diverse factors and comorbidities have been closely associated with PD such as diabetes, obesity, aging, hypertension, and so on; although, underlying mechanisms or causal associations have not been established completely. Interestingly, these same factors have been widely associated with progression or severe coronavirus disease 2019 (COVID-19), an illness caused by coronavirus SARS-CoV-2. Since inflammatory and dysbiotic factors as well as comorbidities affect systemic health, it is possible that periodontal status indicates the risk of complication of COVID-19. However, assessment of oral health history including periodontal status in COVID-19 patients has not been reported. Knowing PD is associated with severe COVID-19 could help identify risk groups and establish pertinent recommendations.

Liver cirrhosis contributes to the disorder of gut microbiota in patients with hepatocellular carcinoma.

BACKGROUND: Gut microbiota (GM) of patients with liver cancer is disordered, and syet no study reported the GM distribution of liver cirrhosis-induced HCC (LC-HCC) and nonliver cirrhosis-induced HCC (NLC-HCC). In this study, we aimed to characterize gut dysbiosis of LC-HCC and NLC-HCC to elucidate the role of GM in the pathogenesis of HCC. METHODS: A consecutive series of fecal samples of patients with hepatitis (24 patients), liver cirrhosis (24 patients), HCC (75 patients: 35 infected by HBV, 25 infected by HCV, and 15 with alcoholic liver disease), and healthy controls (20 patients) were obtained and sequenced on the Illumina Hiseq platform. The HCC group contains 52 LC-HCC and 23 NLC-HCC. Bioinformatic analysis of the intestinal microbiota was performed with QIIME and MicrobiomeAnalyst. RESULTS: Alpha-diversity analysis showed that fecal microbial diversity was significantly decreased in the LC group, and there were significant differences in 3 phyla and 27 genera in the LC group vs the other groups (the healthy, hepatitis, and HCC groups). Beta-diversity analysis showed that there were large differences between LC and the others. Gut microbial diversity was significantly increased from LC to HCC. Characterizing the fecal microbiota of LC-HCC and NLC-HCC, we found that microbial diversity was increased from LC to LC-HCC rather than NLC-HCC. Thirteen genera were discovered to be associated with the tumor size of HCC. Three biomarkers (Enterococcus, Limnobacter, and Phyllobacterium) could be used for precision diagnosis. We also found that HBV infection, HCV infection, or ALD (alcoholic liver disease) was not associated with intestinal microbial dysbiosis in HCC. CONCLUSION: Our results suggest that GM disorders are more common in patients with LC-HCC. The butyrate-producing genera were decreased, while genera producing-lipopolysaccharide (LPS) were increased in LC-HCC patients. Further studies of GM disorders may achieve early diagnosis and new therapeutic approaches for HCC patients.

HIV, Sexual Orientation, and Gut Microbiome Interactions.

Recent studies have raised interest in the possibility that dysbiosis of the gut microbiome (i.e., the communities of bacteria residing in the intestine) in HIV-infected patients could contribute to chronic immune activation, and, thus, to elevated mortality and increased risk of inflammation-related clinical diseases (e.g., stroke, cardiovascular disease, cancer, long-bone fractures, and renal dysfunction) found even in those on effective antiretroviral therapy. Yet, to date, a consistent pattern of HIV-associated dysbiosis has not been identified. What is becoming clear, however, is that status as a man who has sex with men (MSM) may profoundly impact the structure of the gut microbiota, and that this factor likely confounded many HIV-related intestinal microbiome studies. However, what factor associated with MSM status drives these gut microbiota-related changes is unclear, and what impact, if any, these changes may have on the health of MSM is unknown. In this review, we outline available data on changes in the structure of the gut microbiome in HIV, based on studies that controlled for MSM status. We then examine what is known regarding the gut microbiota in MSM, and consider possible implications for research and the health of this population. Lastly, we discuss knowledge gaps and needed future studies.

Aberrant cervical innate immunity predicts onset of dysbiosis and sexually transmitted infections in women of reproductive age.

Sexually transmitted infections (STIs) and vaginal dysbiosis (disturbed resident microbiota presenting with abnormal Nugent score or candidiasis) have been associated with mucosal inflammation and risk of HIV-1 infection, cancer and poor reproductive outcomes. To date, the temporal relationships between aberrant cervical innate immunity and the clinical onset of microbial disturbance have not been studied in a large population of reproductive age women. We examined data from a longitudinal cohort of 934 Ugandan and Zimbabwean women contributing 3,274 HIV-negative visits who had complete laboratory, clinical and demographic data. Among those, 207 women later acquired HIV, and 584 women were intermittently diagnosed with C. trachomatis (CT), N. gonorrhoeae (NG), genital herpes (HSV-2), T. vaginalis (TV), candidiasis, and abnormal intermediate (4-6) or high (7-10) Nugent score, i.e. bacterial vaginosis (BV). Immune biomarker concentrations in cervical swabs were analyzed by generalized linear and mixed effect models adjusting for site, age, hormonal contraceptive use (HC), pregnancy, breastfeeding, genital practices, unprotected sex and overlapping infections. High likelihood ratios (1.5-4.9) denoted the values of cervical immune biomarkers to predict onset of abnormal Nugent score and candidiasis at the next visits. When controlling for covariates, higher levels of ß-defensin-2 were antecedent to BV, CT and HSV-2, lower anti-inflammatory ratio IL-1RA:IL-1ß-to intermediate Nugent scores and candida, lower levels of the serine protease inhibitor SLPI-to candida, lower levels of the adhesion molecule ICAM-1 -to TV, and lower levels of the oxidative stress mitigator and endothelial activation marker VEGF-to NG. Changes in innate immunity following onset of dysbiosis and infections were dependent on HC use when controlling for all other covariates. In conclusion, imminent female genital tract dysbiosis or infection can be predicted by distinct patterns of innate immunity. Future research should characterize biotic and abiotic determinants of this pre-existing innate immunity state.

Composition of Gut Microbiota of Children and Adolescents With Perinatal Human Immunodeficiency Virus Infection Taking Antiretroviral Therapy in Zimbabwe.

BACKGROUND: Human immunodeficiency virus (HIV) infection causes impairment of the gastrointestinal barrier, with substantial depletion of CD4+ T cells in the gut. Antiretroviral therapy (ART) restores CD4+ counts and may have beneficial effects on gut microbiota in adults. Little is known about effect of long-term ART on gut microbiome in HIV-infected children. We investigated composition of gut microbiota in HIV-infected and -uninfected children and assessed associations between gut microbiota and patient characteristics. METHODS: In a cross-sectional study, rectal swabs were collected from 177 HIV-infected and 103 HIV-uninfected controls. Gut microbial composition was explored using 16S ribosomal ribonucleic acid sequencing. RESULTS: Human immunodeficiency virus-infected children had significantly lower alpha-diversity and higher beta-diversity compared to HIV-uninfected. No association was observed between microbiome diversity and CD4+ T-cell count, HIV viral load, or HIV-associated chronic lung disease. We found enriched levels of Corynebacterium (P < .01), Finegoldia (P < .01), and Anaerococcus (P < .01) in HIV-infected participants and enrichment of Enterobacteriaceae (P = .02) in participants with low CD4+ counts (<400 cells/mm3). Prolonged ART-treatment (≥10 years) was significantly associated with a richer gut microbiota by alpha diversity. CONCLUSIONS: Human immunodeficiency virus-infected children have altered gut microbiota. Prolonged ART may restore the richness of the microbiota closer to that of HIV-uninfected children.

Our Little Friends with Big Roles: Alterations of the Gut Microbiota in Thyroid Disorders.

BACKGROUND: The thyroid gland influences the metabolic processes in our body by producing thyroid hormones, and thyroid disorders can range from a harmless goiter to life-threatening cancer. A growing number of evidence support the link between gut microbiota composition and thyroid homeostasis. Gut dysbiosis can disrupt the normal gut barrier function, leading to immunologic and metabolic disorders. OBJECTIVE: The aim of this review was to discuss the main features of gut dysbiosis associated with different thyroid disorders. RESULTS: Gut microbiota contributes to thyroid hormone synthesis and hydrolysis of thyroid hormones conjugates. It has been shown that microbial metabolites may play a role in autoimmune thyroid diseases via modulating the immune system. Intestinal microbiota can contribute to the thyroid malignancies via controlling DNA damage and apoptosis and influencing inflammatory reactions by the microbiota- derived metabolites. However, the pathogenic role of altered gut microbiota in different thyroid disorders has not yet fully elucidated. CONCLUSION: Further research is needed to assess the role of alterations of the gut microbiota in disease onset and development in order to achieve novel strategies for the prevention and treatment of these diseases.