Gut Microbiome Dysbiosis and Immunometabolism: New Frontiers for Treatment of Metabolic Diseases.

Maintenance of healthy human metabolism depends on a symbiotic consortium among bacteria, archaea, viruses, fungi, and host eukaryotic cells throughout the human gastrointestinal tract. Microbial communities provide the enzymatic machinery and the metabolic pathways that contribute to food digestion, xenobiotic metabolism, and production of a variety of bioactive molecules. These include vitamins, amino acids, short-chain fatty acids (SCFAs), and metabolites, which are essential for the interconnected pathways of glycolysis, the tricarboxylic acid/Krebs cycle, oxidative phosphorylation (OXPHOS), and amino acid and fatty acid metabolism. Recent studies have been elucidating how nutrients that fuel the metabolic processes impact on the ways immune cells, in particular, macrophages, respond to different stimuli under physiological and pathological conditions and become activated and acquire a specialized function. The two major inflammatory phenotypes of macrophages are controlled through differential consumption of glucose, glutamine, and oxygen. M1 phenotype is triggered by polarization signal from bacterial lipopolysaccharide (LPS) and Th1 proinflammatory cytokines such as interferon-γ, TNF-α, and IL-1ß, or both, whereas M2 phenotype is triggered by Th2 cytokines such as interleukin-4 and interleukin-13 as well as anti-inflammatory cytokines, IL-10 and TGFß, or glucocorticoids. Glucose utilization and production of chemical mediators including ATP, reactive oxygen species (ROS), nitric oxide (NO), and NADPH support effector activities of M1 macrophages. Dysbiosis is an imbalance of commensal and pathogenic bacteria and the production of microbial antigens and metabolites. It is now known that the gut microbiota-derived products induce low-grade inflammatory activation of tissue-resident macrophages and contribute to metabolic and degenerative diseases, including diabetes, obesity, metabolic syndrome, and cancer. Here, we update the potential interplay of host gut microbiome dysbiosis and metabolic diseases. We also summarize on advances on fecal therapy, probiotics, prebiotics, symbiotics, and nutrients and small molecule inhibitors of metabolic pathway enzymes as prophylactic and therapeutic agents for metabolic diseases.

Androgen and Estrogen Shifts in Men Before and After Bariatric Surgery and Links to Vitamins and Trace Elements.

Androgens and estrogens play a key role regarding sexual life and reproduction. Along with hypotestosteronemia, obese men exhibit a 2-fold increase in estradiol concentration, adversely infl uencing these parameters. Estrogens and adipokines also infl uence bone metabolism, exerting a direct effect on vitamin D, calcium homeostasis and bone health. Bariatric procedures normalize some sex hormones, and may reverse several obesity-related conditions. Estrogens levels may remain elevated postoperatively, and despite its protective effect on the skeleton, bariatric patients are more prone to fractures when compared to the general population. Multiple nutritional defi cits are common after bariatric interventions, and hypozincemia is the most likely to negatively infl uence reproductive parameters. Zinc is an essential element for normal spermatogenesis, and severe hypozincemia is associated with infertility in both sexes. Vitamin D also acts as a regulator of several enzymes involved in steroid hormone production, and its defi ciency could impair reproductive function. Few studies have addressed changes in sex hormones and in reproductive function in the male bariatric population, as they represent a minority of surgical candidates. Although obesity rates and burden are similar for both sexes, society is more lenient with the obese male. Moreover, 73 % of overweight/obese men are satisfi ed with their health, causing body weight and obesity-related health problems to increase when they opt for bariatric surgery. In the present article, we discuss shifts of sex hormones before and after bariatric surgery, surgery impact on semen quality, skeletal health and nutrients, and new research directions regarding links between vitamin D, zinc, androgens and reproduction.

Evolving endoscopic surgery.

Since the days of Albukasim in medieval Spain, natural orifices have been regarded not only as a rather repugnant source of bodily odors, fluids and excreta, but also as a convenient invitation to explore and treat the inner passages of the organism. However, surgical ingenuity needed to be matched by appropriate tools and devices. Lack of technologically advanced instrumentation was a strong deterrent during almost a millennium until recent decades when a quantum jump materialized. Endoscopic surgery is currently a vibrant and growing subspecialty, which successfully handles millions of patients every year. Additional opportunities lie ahead which might benefit millions more, however, requiring even more sophisticated apparatuses, particularly in the field of robotics, artificial intelligence, and tissue repair (surgical suturing). This is a particularly exciting and worthwhile challenge, namely of larger and safer endoscopic interventions, followed by seamless and scarless recovery. In synthesis, the future is widely open for those who use together intelligence and creativity to develop new prototypes, new accessories and new techniques. Yet there are many challenges in the path of endoscopic surgery. In this new era of robotic endoscopy, one will likely need a virtual simulator to train and assess the performance of younger doctors. More evidence will be essential in multiple evolving fields, particularly to elucidate whether more ambitious and complex pathways, such as intrathoracic and intraperitoneal surgery via natural orifice transluminal endoscopic surgery (NOTES), are superior or not to conventional techniques.

Do colorectal cancer resections improve diabetes in long-term survivors? A case-control study.

BACKGROUND: A clinical study was designed that aimed to analyze whether resection of the large bowel in cancer patients might benefit diabetes mellitus. METHODS: This prospective case-control study included retrospective information. Patients (n = 247) included diabetic and euglycemic groups with colorectal cancer operations (n = 60), cancer gastrectomy (n = 72), exclusive chemoradiotherapy for rectal cancer (n = 46), and noncancer clinical controls (n = 69). Follow-up periods were, respectively, 79.2 ± 27.4, 86.8 ± 25.1, 70.0 ± 26.3, and 85.1 ± 18.2 months (NS). Diabetes groups included patients with prediabetes. RESULTS: Diabetes remission, defined as conversion from diabetes to prediabetes or from this condition to normal, was documented in, respectively, 32.4 % (11 of 34), 41.2 % (14 of 34), 7.1 % (1 of 14), and 7.7 % (3 of 39) in the four cohorts (P = 0.004). Within the same period, progression of euglycemic participants to diabetes occurred in 30.8 % (8 of 26), 63.2 % (24 of 38), 25.0 (8 of 32), and 20.0 % (6 of 30) (P = 0.028). Diabetes amelioration was associated with weight loss in gastrectomy patients but not in the other groups. Dietary intake, estimated in the two surgical populations, did not predict outcome. CONCLUSIONS: Diabetes amelioration after colorectal interventions was demonstrated, but progression of euglycemic patients toward prediabetes was not changed in comparison with nonsurgical controls. It is speculated that reshaping of the bowel microbiome or hormone changes after colorectal interventions underlay the improvement in diabetes. Body weight fluctuations could not be incriminated in this investigation.

Does Roux-en-Y gastrectomy for gastric cancer influence glucose homeostasis in lean patients?

BACKGROUND: Cancer gastrectomy seems to benefit type 2 diabetes; however, results are conflicting. In a prospective protocol, including retrospective information, the aim was assessment of changes in glucose profile in patients with both normal and deranged preoperative glucose homeostasis. METHODS: Patients (N = 164) with curative subtotal or total Roux-en-Y gastrectomy for gastric cancer (n = 92), or Roux-en-Y gastric bypass for morbid obesity (RYGB, n = 72) were preoperatively classified into diabetes (including prediabetes) and control group. Postoperative diabetes outcome was stratified as responsive or refractory, and results in controls were correspondingly defined as stable or new-onset diabetes (NOD), according to fasting blood glucose and HbA1c. Dietary intake and biochemical profile was documented. Statistical methods included analysis of variance, multivariate logistic regression, and propensity score matching according to postoperative weight loss. RESULTS: Age of cancer cases was 67.9 ± 11.5 years, 56.5 % males, initial body mass index (BMI) 24.7 ± 3.7, current BMI 22.6 ± 3.8 kg/m(2), and follow-up 102.1 ± 51.0 months, whereas in bariatric individuals age was 51.4 ± 10.1 years, 15.3 % males, initial BMI 56.7 ± 12.2, current BMI 34.8 ± 8.1 kg/m(2), and follow-up 104.1 ± 29.7 months. Refractory disease corresponded to 62.5 % (cancer) versus 23.5 % (bariatric) (P = 0.019), whereas NOD represented 69.2 versus 23.8 % respectively (P = 0.016). Weight loss (ΔBMI) was associated with diabetes response in cancer patients but not with NOD. No difference between subtotal and total gastrectomy was detected. Divergent outcomes (refractory vs. responsive) were confirmed in BMI-similar, propensity-matched cancer gastrectomy patients with preoperative diabetes, consistent with weight-dependent and -independent benefits. CONCLUSIONS: Diabetes response was confirmed, however with more refractory cases than in bariatric controls, whereas high proportions of NOD occurred. Such dichotomous pattern seems unusual albeit consistent with previous studies.

Lung microbiome and origins of the respiratory diseases.

The studies on the composition of the human microbiomes in healthy individuals, its variability in the course of inflammation, infection, antibiotic therapy, diets and different pathological conditions have revealed their intra and inter-kingdom relationships. The lung microbiome comprises of major species members of the phylum Bacteroidetes, Firmicutes, Actinobacteria, Fusobacteria and Proteobacteria, which are distributed in ecological niches along nasal cavity, nasopharynx, oropharynx, trachea and in the lungs. Commensal and pathogenic species are maintained in equilibrium as they have strong relationships. Bacterial overgrowth after dysbiosis and/or imbalanced of CD4+ helper T cells, CD8+ cytotoxic T cells and regulatory T cells (Treg) populations can promote lung inflammatory reactions and distress, and consequently acute and chronic respiratory diseases. This review is aimed to summarize the latest advances in resident lung microbiome and its participation in most common pulmonary infections and pneumonia, community-acquired pneumonia (CAP), ventilator-associated pneumonia (VAP), immunodeficiency associated pneumonia, SARS-CoV-2-associated pneumonia, acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD). We briefly describe physiological and immunological mechanisms that selectively create advantages or disadvantages for relative growth of pathogenic bacterial species in the respiratory tract. At the end, we propose some directions and analytical methods that may facilitate the identification of key genera and species of resident and transient microbes involved in the respiratory diseases' initiation and progression.

Refractory and new-onset diabetes more than 5 years after gastric bypass for morbid obesity.

BACKGROUND: Few studies about long-term glucose homeostasis in bariatric patients are available. In a prospective protocol that included retrospective information, outcome of patients with both impaired and normal fasting blood glucose (FBG) was monitored to assess frequencies and correlates. METHODS: Patients submitted to Roux-en-Y gastric bypass were classified as group I, elevated FBG, and group II, normal controls. Those in group I with improvement in FBG were defined as responsive and the others as refractory. Group II participants progressing to new-onset diabetes (NOD) or prediabetes represented NOD cases; the remaining were listed as stable controls. FBG was the main endpoint, but HbA1c results were considered, along with diet composition and general biochemical profile. RESULTS: Among 97 selected patients, 51 belonged to group I (52.4 ± 10.5 years, 29.6 % males, initial body mass index (BMI) 58.4 ± 13.4, current BMI 35.1 ± 8.4 kg/m(2)) and 46 to group II (48.2 ± 10.5 years, 19.6 % males, initial BMI 55.5 ± 8.8, current BMI 33.9 ± 6.9 kg/m(2)). Follow-up was 7-9 years, and 31.4 % (16/51) of group I were classified as refractory, whereas 15.2 % (7/46) of the controls converted to NOD. Multivariate analysis pointed out higher current BMI, older age, consumption of antidiabetic drugs, and male gender as features of refractory cases, whereas NOD participants were not significantly different from non-progressing controls. CONCLUSIONS: This is the first investigation, to the best of our knowledge, to underscore the correlates of refractory and NOD within the bariatric context. Further studies are recommended as such information could be valuable for patient selection, prognostic scoring, and outcome monitoring.

Microbiome systems biology advancements for natural well-being.

Throughout the years all data from epidemiological, physiological and omics have suggested that the microbial communities play a considerable role in modulating human health. The population of microorganisms residing in the human intestine collectively known as microbiota presents a genetic repertoire that is higher in magnitude than the human genome. They play an essential role in host immunity and neuronal signaling. Rapid enhancement of sequence based screening and development of humanized gnotobiotic model has sparked a great deal of interest among scientists to probe the dynamic interactions of the commensal bacteria. This review focuses on systemic analysis of the gut microbiome to decipher the complexity of the host-microbe intercommunication and gives a special emphasis on the evolution of targeted precision medicine through microbiome engineering. In addition, we have also provided a comprehensive description of how interconnection between metabolism and biochemical reactions in a specific organism can be obtained from a metabolic network or a flux balance analysis and combining multiple datasets helps in the identification of a particular metabolite. The review highlights how genetic modification of the critical components and programming the resident microflora can be employed for targeted precision medicine. Inspite of the ongoing debate on the utility of gut microbiome we have explored on the probable new therapeutic avenues like FMT (Fecal microbiota transplant) can be utilized. This review also recapitulates integrating human-relevant 3D cellular models coupled with computational models and the metadata obtained from interventional and epidemiological studies may decipher the complex interactome of diet-microbiota-disease pathophysiology. In addition, it will also open new avenues for the development of therapeutics derived from microbiome or implementation of personalized nutrition. In addition, the identification of biomarkers can also help towards the development of new diagnostic tools and eventually will lead to strategic management of the disease. Inspite of the ongoing debate on the utility of the gut microbiome we have explored how probable new therapeutic avenues like FMT (Fecal microbiota transplant) can be utilized. This review also summarises integrating human-relevant 3D cellular models coupled with computational models and the metadata obtained from interventional and epidemiological studies may decipher the complex interactome of diet- microbiota-disease pathophysiology. In addition, it will also open new avenues for the development of therapeutics derived from the microbiome or implementation of personalized nutrition. In addition, the identification of biomarkers can also help towards the development of new diagnostic tools and eventually will lead to strategic management of disease.

Bioimpedance analysis: should it be used in morbid obesity?

OBJECTIVES: Questions about reliability of bioimpedance analysis (BIA) in morbidly obese subjects have curtailed its use in this setting, but metabolic implications might reignite the debate. In a prospective study, it was aimed to analyze anthropometric and clinical associations. METHODS: Bariatric candidates (n = 94) with or without metabolic syndrome were consecutively investigated. Age was 34.9 ± 10.4 years (68.1% females), and BMI was 40.8 ± 4.6 kg m(-2) . Methods included single-frequency BIA, anthropometrics, inflammatory indices, and general biochemical profile. RESULTS: Body composition results (water, fat) in females, but not in males, were entirely consistent with the literature. In both genders good association was observed with anthropometrics (BMI, waist circumference), inflammatory indices (ferritin, C-reactive protein) and general biochemical variables. Anthropometric measurements also displayed comparable associations. Multivariate tests including the two sets of measurements indicated no predominance of one method over the other, one complementing the other as metabolic marker. CONCLUSIONS: BIA limitations were mostly relevant for males, not females. Despite such discrepancies, good associations with anthropometry were demonstrated for both genders. Correlations with liver enzymes, and indices of protein, carbohydrate, and lipid metabolism could be demonstrated. BIA deserves more investigations concerning liver steatosis and ongoing inflammation, and it could contribute as well, synergistically with anthropometry, to monitor weight loss, body fat shifts, and metabolic risk.

Systemic inflammatory reaction after silicone breast implant.

BACKGROUND: Systemic inflammation after augmentation mammaplasty with modern silicone implants is not currently recognized. In a prospective controlled study, C-reactive protein and other variables were monitored, aiming to test this hypothesis in a young cohort of patients. METHODS: Females (18-30 years old, BMI = 18.5-30 kg/m(2), N = 52) were consecutively recruited for breast implant (n = 24, Group I) and for abdominal liposuction (n = 28, Group II/Controls). Patients were interviewed at baseline and followed until 6 months after operation. Variables included demographic and clinical information, surgical outcome, inflammatory markers and autoantibodies. RESULTS: Operations were well tolerated, without surgical or infectious complications. Mean prosthesis size was 258 ± 21 ml (range = 220-280) and mean aspirate of liposuction was 1972 ± 499 ml (range = 1200-3000). Preoperative, 2-month, and 6-month C-reactive protein concentrations for breast implant patients were 1.3 ± 1.2, 4.8 ± 3.0, and 4.3 ± 6.4 mg/l and for liposuction 3.5 ± 2.7, 3.5 ± 2.1, and 2.2 ± 2.2 mg/l, respectively. Change at 2 months was significant (p = 0.001). Autoantibody investigation failed to reveal remarkable aberrations, except for anticardiolipin elevation, which was nearly symmetrical in the two groups. CONCLUSION: C-reactive protein levels increased after operation and correlated with proinflammatory and procoagulatory indices. A mild increase in anticardiolipin IgM occurred but differences between populations were lacking. Despite excellent cosmetic outcomes and lack of complications, acute phase reaction could signal ongoing immunogenicity of silicone and long-term monitoring is recommended.

Breath Biopsy and Discovery of Exclusive Volatile Organic Compounds for Diagnosis of Infectious Diseases.

Exhaled breath contains thousand metabolites and volatile organic compounds (VOCs) that originated from both respiratory tract and internal organ systems and their microbiomes. Commensal and pathogenic bacteria and virus of microbiomes are capable of producing VOCs of different chemical classes, and some of them may serve as biomarkers for installation and progression of various common human diseases. Here we describe qualitative and quantitative methods for measuring VOC fingerprints generated by cellular and microbial metabolic and pathologic pathways. We describe different chemical classes of VOCs and their role in the host cell-microbial interactions and their impact on infection disease pathology. We also update on recent progress on VOC signatures emitted by isolated bacterial species and microbiomes, and VOCs identified in exhaled breath of patients with respiratory tract and gastrointestinal diseases, and inflammatory syndromes, including the acute respiratory distress syndrome and sepsis. The VOC curated databases and instrumentations have been developed through statistically robust breathomic research in large patient populations. Scientists have now the opportunity to find potential biomarkers for both triage and diagnosis of particular human disease.

Treating short bowel syndrome with pharmacotherapy.

INTRODUCTION: Short bowel syndrome (SBS) has traditionally been regarded as a rapidly fatal medical catastrophe. The advent of pharmacological options directly targeting disease pathophysiology justified this review. AREAS COVERED: Since the 1970s, home parenteral nutrition has reduced mortality, converting SBS into a chronic and disabling compensated and occasionally curable illness. Off-label antidiarrheal drugs and related products, though having minimal scientific evidence of efficacy, represent the standard-of-care and are here reviewed. Trophic intestinal hormones, including GLP-2 and its analogs, have great promise for alleviating malabsorption, the most important symptom within a nonsurgical, routine outpatient framework. Current indications involve adults with massive intestinal losses (fecal wet weight >1500 g/day). Surgical options such as intestinal lengthening or transplantation are also addressed although these options are considerably more aggressive and have stricter indications. EXPERT OPINION: GLP-2 analogs are the first candidates from a pioneering pharmacotherapic family within the SBS framework, namely disease-modifying, absorption-restoring agents. This family of drugs, potentially applicable in all contexts of severe intestinal loss, could become the therapeutic benchmark of the near future.

Pregnancy nutritional indices and birth weight after Roux-en-Y gastric bypass.

BACKGROUND: Maternal metabolic profile and nutritional course of pregnancy after bariatric interventions is incompletely known. Their impact on birth weight has also not been hitherto addressed. Aiming to document such variables, a retrospective study was undertaken. METHODS: Women previously submitted to silastic ring Roux-en-Y gastric bypass, who conceived after 0-5 years (n = 14), were investigated. Intake of selected macro- and micronutrients, representative laboratory measurements, and correlation of these findings with birth weight and time to conception was documented. RESULTS: Mean calorie intake was restricted to about 1,800 kcal/day. Protein (71 +/- 17 g/day) and supplementary iron (60 mg/day) were barely adequate, and calcium and vitamin B(12) did not meet current recommendations, only folic acid being optimal. Biochemical monitoring reflected these inconsistencies, with occasional low values for serum albumin (4.1 +/- 0.4 g/dL), hemoglobin (11.4 +/- 1.5 g/dL), iron (78 +/- 50 mug/dL) and vitamin B(12) (193 +/- 102 pg/mL) but not folate. Lipids, glucose, and uric acid were much better than before the anti-obesity intervention. Reduced plasma lipids, glucose, and uric acid were associated with larger birth weight, albeit within the normal range. CONCLUSIONS: (1) Anemia as well as additional nutritional deficits during pregnancy were not totally eliminated, despite dietary guidance and micronutrient supplementation; (2) alleviation of metabolic comorbidities was demonstrated, and improved normalization predicted higher birth weight; (3) energy and folate intake was sufficient, but other nutrients probably did not reach ideal levels; (4) recent dietary guidelines for this population represent a step forward, but additional studies are needed.

Is splenectomy a dyslipidemic intervention? Experimental response of serum lipids to different diets and operations.

UNLABELLED: Spleen removal may be recommended during organ transplantation in ABO-incompatible recipients as well as for hypoperfusion of the grafted liver, besides conventional surgical indications, but elevation of serum lipids has been observed in certain contexts. Aiming to analyze the influence of two dietary regimens on lipid profile, an experimental study was conducted. METHODS: Male Wistar rats (n = 86, 333.0 +/- 32.2 g) were divided in four groups: group 1: controls; group 2: sham operation; group 3: total splenectomy; group 4: subtotal splenectomy with upper pole preservation; subgroups A (cholesterol reducing chow) and B (cholesterol-rich mixture) were established, and diet was given during 90 days. Total cholesterol (Tchol), high-density lipoprotein (HDL), low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), and triglycerides were documented. RESULTS: After total splenectomy, hyperlipidemia ensued with cholesterol-reducing chow. Tchol, LDL, VLDL, triglycerides, and HDL changed from 56.4 +/- 9.2, 24.6 +/- 4.7, 9.7 +/- 2.2, 48.6 +/- 11.1, and 22.4 +/- 4.3 mg/dL to 66.9 +/- 11.4, 29.9 +/- 5.9, 10.9 +/- 2.3, 54.3 +/- 11.4, and 26.1 +/- 5.1 mg/dL, respectively. Upper pole preservation inhibited abnormalities of Tchol, HDL, VLDL, and triglycerides, and LDL decreased (23.6 +/- 4.9 vs. 22.1 +/- 5.1, P = 0.002). Higher concentrations were triggered by splenectomy and cholesterol-enriched diet (Tchol 59.4 +/- 10.1 vs. 83.9 +/- 14.3 mg/dL, P = 0.000), and upper-pole preservation diminished without abolishing hyperlipidemia (Tchol 55.9 +/- 10.0 vs. 62.3 +/- 7.8, P = 0.002). CONCLUSIONS: After splenectomy, hyperlipidemia occurred with both diets. Preservation of the upper pole tended to correct dyslipidemia in modality A and to attenuate it in subgroup B.

Potential premalignant status of gastric portion excluded after Roux en-Y gastric bypass in obese women: A pilot study.

We evaluated whether the excluded stomach (ES) after Roux-en-Y gastric bypass (RYGB) can represent a premalignant environment. Twenty obese women were prospectively submitted to double-balloon enteroscopy (DBE) with gastric juice and biopsy collection, before and 3 months after RYGB. We then evaluated morphological and molecular changes by combining endoscopic and histopathological analyses with an integrated untargeted metabolomics and transcriptomics multiplatform. Preoperatively, 16 women already presented with gastric histopathological alterations and an increased pH (≥4.0). These gastric abnormalities worsened after RYGB. A 90-fold increase in the concentration of bile acids was found in ES fluid, which also contained other metabolites commonly found in the intestinal environment, urine, and faeces. In addition, 135 genes were differentially expressed in ES tissue. Combined analysis of metabolic and gene expression data suggested that RYGB promoted activation of biological processes involved in local inflammation, bacteria overgrowth, and cell proliferation sustained by genes involved in carcinogenesis. Accumulated fluid in the ES appears to behave as a potential premalignant environment due to worsening inflammation and changing gene expression patterns that are favorable to the development of cancer. Considering that ES may remain for the rest of the patient's life, long-term ES monitoring is therefore recommended for patients undergoing RYGB.

Systemic inflammation and cardiovascular risk factors: are morbidly obese subjects different?

BACKGROUND: Systemic inflammation is a hallmark of obesity as well as of other chronic diseases, usually indicating increased cardiovascular risk; however, studies with arterial documentation in morbid obesity are extremely scarce. Aiming to analyze correlation between inflammatory markers, pulse-wave velocity (PWV), and intima-media thickness (IMT), a prospective study was designed. METHODS: Morbidly obese patients [n = 29, age 46.3 +/- 5.2 years, 82.8% females (24/29), BMI 44.9 +/- 5.2 kg/m(2)] with C-reactive protein/CRP > 5 mg/l but free from trauma, infection, inflammation, or cancer were enrolled in this study. All were clinically stable candidates for elective bariatric operation. Variables included comorbidities, metabolic profile, inflammatory and coagulatory markers, and arterial morpho-functional indices. RESULTS: Patients suffered from arterial hypertension (72.4%), metabolic syndrome (58.6%), and other comorbidities, but PWV and IMT were less aberrant than expected. Univariate correlation confirmed worse prognosis for those with metabolic syndrome and other accepted clinical risk factors. Multivariate confirmation was achieved for triglycerides (PWV) and D-dimer (IMT), but not for CRP, serum amyloid A, or neutrophil count, which were reversed in certain circumstances. CONCLUSIONS: (1) Metabolic syndrome, hyperglycemia, hypertriglyceridemia and D-dimer were positively correlated with arterial measurements, whereas inflammatory and coagulatory markers often exhibited paradoxical association; (2) stratification confirmed that at certain levels of systemic inflammation or body mass index, acute phase proteins and other markers became unreliable or shifted signals; (3) when controlled for blood pressure, PWV was only moderately elevated, and IMT remained normal; (4) taken together, these findings are consistent with a unique interaction between adiposity, inflammation, and cardiovascular risk in seriously obese subjects.

Quality of life after abdominoplasty in women after bariatric surgery.

BACKGROUND: Abdominal skin overhang is not unusual after massive weight loss induced by antiobesity interventions, and poor quality of life should be feared in such circumstances, especially in women. However, long-term results of quality of life have not been often documented in this setting. With the purpose of addressing this question, a prospective study was designed. METHODS: Patients (n = 16, 100% females, age 40.1 +/- 8.0 years) submitted to standard or combined circumferential abdominoplasty were recruited for this study. All had undergone open Roux-en-Y gastric bypass between 24 and 48 months earlier with stable weight in the last 12 months. Quality of life was assessed by a trained psychologist employing of a semistructured interview, the Adaptative Operationalized Diagnostic Scale (AODS), covering affectivity/personal relations, productivity, social/cultural performance, and organic/somatic health. RESULTS: Circumferential abdominoplasty was followed by few problems (serous fluid collections in 18.8%, anemia because of blood loss in 6.3%). The best overall response to the AODS questionnaire corresponded to the social and cultural domain where 81.3% of the patients had excellent adaptation (level 1). For the other three domains, results were remarkably similar with 62.5% of the tests displaying the highest value of adaptation and rare total failures. CONCLUSIONS: (1) The current operation corresponded to the expectations of the patients with few complications and favorable body contouring result. (2) Quality of life, quantified by means of adaptation and social adjustment scores, was adequate in most circumstances. (3) Outstanding responses for social/cultural performance were registered with encouraging findings for affectivity/personal relations, productivity, and organic/somatic health as well.

High-fat diet: a trigger of non-alcoholic steatohepatitis? Preliminary findings in obese subjects.

OBJECTIVE: We correlated dietary profile and markers of visceral and somatic obesities in non-alcoholic fatty liver disease. METHODS: Patients with histologically proven fatty infiltration of the liver (n = 25, 52 +/- 11 y of age, 64% women) underwent abdominal computed tomography, bioelectrical impedance, and anthropometric measurements. Insulin resistance was evaluated (homeostasis model assessment) and dietary intake of macronutrients was estimated by 24-h recall. Main outcome measurements were correlation of carbohydrate and fat ingestion with liver histology. RESULTS: Metabolic syndrome was present in 72% of the population, and increased waist circumference and low high-density lipoprotein cholesterol occurred in 66%. Total body fat (bioimpedance) and dietary intake of lipids were higher in patients with non-alcoholic steatohepatitis (P < 0.05), but not in diabetic subjects who exhibited more steatosis than non-alcoholic steatohepatitis. Waist circumference exhibited a good correlation with homeostasis model assessment, total energy intake, and ingestion of specific fatty acids. Body mass index correlated well with somatic and visceral adiposities. CONCLUSION: Energy intake and visceral adiposity were predisposing factors for fatty liver disease. Lipid input correlated with non-alcoholic steatohepatitis in the entire group and after stratification for diabetes. These findings suggest that lipid intake may play a greater role in non-alcoholic steatohepatitis than hitherto suspected.

Correction to: Biography: Joel Faintuch, MD, PhD.

In the original article the photo of Dr. Faintuch was inadvertently omitted. We apologize for this oversight.

Microbiome and Gut Dysbiosis.

The gastrointestinal (GI) tract is the residence of trillions of microorganisms that include bacteria, archaea, fungi and viruses. The collective genomes of whole microbial communities (microbiota) integrate the gut microbiome. Up to 100 genera and 1000 distinct bacterial species were identified in digestive tube niches. Gut microbiomes exert permanent pivotal functions by promoting food digestion, xenobiotic metabolism and regulation of innate and adaptive immunological processes. Proteins, peptides and metabolites released locally and at distant sites trigger many cell signalling and pathways. This intense crosstalk maintains the host-microbial homeostasis. Diet, age, diet, stress and diseases cause increases or decreases in relative abundance and diversity bacterial specie of GI and other body sites. Studies in animal models and humans have shown that a persistent imbalance of gut's microbial community, named dysbiosis, relates to inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS), diabetes, obesity, cancer, cardiovascular and central nervous system disorders. Notably specific bacterial communities are promising clinical target to treat inflammatory and infectious diseases. In this context, intestinal microbiota transplantation (IMT) is one optional treatment for IBD, in particular to patients with recurrent Clostridium difficile-induced pseudo-membrane colitis. Here we discuss on recent discoveries linking whole gut microbiome dysbiosis to metabolic and inflammatory diseases and potential prophylactic and therapeutic applications of faecal and phage therapy, probiotic and prebiotic diets.