Cholesterol Gallstones and Long-Term Use of Statins: Is Gut Microbiota Dysbiosis Bridging over Uncertainties?

A total of 300 research participants-200 consecutive patients diagnosed with dyslipidemia (100 statin (+), treated for at least five years, and 100 statin (-)) and 100 healthy controls-were included in this observational study. The aim of the study was to deliver insights into the relationship between the long-term use of statins for dyslipidemia and gallstone disease (GSD), as well as insights into the background particularities of the gut microbiota. All study participants underwent clinical examination, laboratory workups, stool microbiology/stool 16S r RNA, next-generation sequencing, and abdominal ultrasound/CT exams. Results: The research participants presented with similarities related to age, gender, and location. Patients displayed comparable heredity for GSs, metabolic issues, and related co-morbidities. Gut dysbiosis (DB) was present in 54% of the statin (-) patients vs. 35% of the statin (+) patients (p = 0.0070). GSs were present in 14% of patients in the statin (-) group vs. 5% of patients in the statin (+) group (p = 0.0304). Severe dysbiosis, with a significant reduction in biodiversity, an increase in LPS (+) bacteria, and a notable decrease in mucin-degrading bacteria, mucosa-protective bacteria, and butyrate-producing bacteria were observed in the statin (-) group. Strong positive correlations between GSD and diabetes/impaired glucose tolerance (r = 0.3368, p = 0.0006), obesity (r = 0.3923, p < 0.0001), nonalcoholic fatty liver disease (r = 0.3219, p = 0.0011), and DB (r = 0.7343, p < 0.0001), as well as significant negative correlations between GSD and alcohol use (r = -0.2305, p = 0.0211), were observed. The multiple regression equation demonstrated that only DB (95% CI: 0.3163 to 0.5670; p < 0.0001) and obesity (95% CI: 0.01431 to 0.2578; p = 0.0289) were independent risk factors predicting GSD in the group of patients treated with statins. Conclusion: The long-term use of statins in dyslipidemic patients was associated with a low risk of developing GSs. The gut microbiota associated with a long-term use of statins in dyslipidemic patients was characterized by a low risk of developing an imbalance of various functional bacteria and alterations in the metabolic microbiota. DB and obesity were found to be independent risk factors predicting GSD in statin (+) patients.

Portal Vein Thrombosis in Patients with Liver Cirrhosis: What Went Wrong?

Purpose: This study aimed to explore inflammatory biomarkers, stool's functional bacterial groups and their possible link to portal vein thrombosis (PVT) in patients with liver cirrhosis (LC). Materials and Methods: An observational study of 300 participants: 200 inhospital cirrhotic patients, who met inclusion criteria, equally assigned into two groups, based on the presence or absence of PVT and 100 healthy controls was carried out. Results: The PVT group displayed significant differences related to older age, cigarettes smoking history, emergency admission, higher Child-Pugh score, metabolic related disorders and nonalcoholic fatty liver disease, as well as non-obstructive aspects, with chronic thrombi. The PVT group exhibited significant differences related to biomarkers such as tumor necrosis factor (TNF)-alpha, C-reactive protein (CRP), D-dimers (D-D), as well as gut overall dysbiosis (DB) and alteration of different functional bacterial groups of the gut microbiota. Strong positive correlations were observed between PVT severity, and TNF-alpha, CRP, D-D as well as lipopolysaccharide (LPS) positive bacteria. Esophageal varices, age and abdominal pain were independent predictors for PVT severity as well as CRP, TNF-alpha and D-D. Conclusion: Patients with LC and PVT displayed elevation of TNF-alpha, CRP, D-D alterations of the functional gut microbiota, as well as several morphological and clinical particularities. Although the LPS positive gut microbiota was linked to inflammatory biomarkers and PVT severity, it was not proven to be an independent predictor of the PVT severity like CRP, TNF-alpha and D-D.

NASH/NAFLD-Related Hepatocellular Carcinoma: An Added Burden.

Hepatocellular carcinoma (HCC) is the most frequently found primary malignancy of the liver, showing an accelerated upward trend over the past few years and exhibiting an increasing relationship with metabolic syndrome, obesity, dyslipidemia and type 2 diabetes mellitus. The connection between these risk factors and the occurrence of HCC is represented by the occurrence of non-alcoholic fatty liver disease (NAFLD) which later, based on genetic predisposition and various triggers (including the presence of chronic inflammation and changes in the intestinal microbiome), may evolve into HCC. HCC in many cases is diagnosed at an advanced stage and can be an incidental finding. We present such a scenario in the case of a 41-year-old male patient who had mild obesity and mixed dyslipidemia, no family or personal records of digestive pathologies and who recently developed a history of progressive fatigue, dyspepsia and mild upper abdominal discomfort initially thought to be linked to post-COVID syndrome, as the patient had COVID-19 pneumonia a month prior. The abdominal ultrasound revealed a mild hepatomegaly with bright liver aspect of the right lobe (diffuse steatosis), a large zone of focal steatosis (segments IV, III and II) and a left lobe tumoral mass, highly suggestive of malignancy. Point shear wave elastography at the right lobe ruled out an end-stage chronic liver disease. Additional laboratory investigations, imaging studies (magnetic resonance imaging) and histopathological examination of liver fragments confirmed a highly aggressive HCC, with poorly differentiation-G3, (T4, N 1M 0) and stage IVA, associated with nonalcoholic steatohepatitis (NASH). A sorafenib course of treatment was attempted, but the patient discontinued it due to severe side effects. The subsequent evolution was extremely unfavorable, with rapid degradation, a few episodes of upper digestive bleeding, hepatic insufficiency and mortality in a couple of months. Conclusions: Diagnosis of NASH-related HCC is either an accidental finding or is diagnosed at an advanced stage. In order to earn time for a proper treatment, it becomes important to diagnose it at an early stage, for which regular check-ups should be performed in groups having the risk factors related to it. Patients suffering from obesity and mixed dyslipidemia should undergo periodic abdominal ultrasound examinations. This should be emphasized even more in the cases showing NASH. Complaints of any kind post-COVID-19 should be dealt with keenly as little is yet known about its virulence and its long-term side effects.

Gallstone Disease and Bacterial Metabolic Performance of Gut Microbiota in Middle-Aged and Older Patients.

Background: Gallstone disease (GSD) is more commonly presented in aged people. Purpose: The purpose of the study was to explore the insights of metabolic performance of bacterial species from gut microbiota as well as the clinical background in middle-aged and elderly patients with GSD. Patients and Methods: This is an observational study concerning 120 research participants. Of those, 90 patients with symptomatic GSD addressed for cholecystectomy, average age 59.83 ± 15.32 years: 45 with cholesterol rich gallstones (CGSs), 45 with pigment gallstones (PGSs) and 30 healthy controls joined this observational study. Clinical examination, lab work-ups, upper and lower digestive video-endoscopies, abdominal ultrasound/CT and gallbladder motility assessment by Dodd's method were performed. Overall stool dysbiosis (DB) was assessed as 1 = minor, 2 = mild, 3 = severe, species being identified by matrix-assisted laser desorption ionization method. Stool samples from dysbiotic patients were analyzed by a next generation sequencing method with operational taxonomic unit identification. Results: Patients with GSD presented with a significant high range of overall gut DB (p < 0.0001) when compared with controls. Those with CGSs compared with those having PGSs displayed significant clinical differences related to elderly age, lifestyle and diet particularities, obesity, dyslipidemia, nonalcoholic fatty liver disease, hypertension, type 2 diabetes mellitus or impaired glucose tolerance, as well as motility disturbances of gallbladder with a decrease of the ejection fraction. Significant increase of overall DB range and alterations of several functional bacterial species with a decrease of butyrate, lactate, acetate/propionate and methane producers, mucin degrading bacteria, biodiversity index of microbiota, as well as an increase of lipopolysaccharide positive bacteria were significantly present in patients with CGSs. Conclusion: Middle-aged and elderly patients with GSD and a clinical background characterized by particular lifestyle, metabolic and gallbladder motility issues displayed significant modifications of biodiversity, overall gut DB and alterations of several functional bacterial species, with a decrease of their metabolic performance.

Dyspepsia and Gut Microbiota in Female Patients with Postcholecystectomy Syndrome.

BACKGROUND: Gallstone disease (GSD) represents one of the most frequent digestive disorders, highly reported in female gender. The purpose of the study was to explore the clinical and gut microbiota particularities of female patients with postcholecystectomy syndrome (PCS) and the possible relationship between gut dysbiosis (DB) and abdominal complaints. PATIENTS AND METHODS: In total, 129 female participants: 104 outpatients divided into two equal groups, 52 PCS (+), 52 PCS (-) and 25 healthy controls were consecutively enrolled in this observational study. Patients underwent clinical examination with assessment of pain, bloating, transit disturbances, abdominal ultrasound/computer tomography/magnetic resonance imaging/endoscopic retrograde cholangiopancreatography, upper and lower digestive endoscopies. Laboratory work-ups and stool microbiology assessments were performed for all study participants (patients and controls). Stool microorganisms were identified by matrix-assisted laser desorption ionization - time-of-flight- mass spectrometry and in patients with DB also by next-generation sequencing. RESULTS: Older age, complicated gallstones disease, associated conditions like diabetes mellitus/impaired glucose tolerance and irritable bowel syndrome were significantly present in PCS (+) group, as well as sedentary lifestyle and diets characterized by a low fiber intake (p<0.0001). PCS (+) patients displayed significant differences related to the incidence and severity of overall gut microbiota DB, decreased H index of biodiversity and the unbalanced Firmicutes/Bacteroidetes (F/B) ratios by comparison to the PCS (-) group (p<0.0001). Strong positive correlations of the severity of overall DB with bloating and the intestinal habit disorders, as well as of F/B ratios to all abdominal symptoms were noted. CONCLUSION: PCS in female patients was associated with older age, sedentary lifestyle, specific dietary habits, history of complicated gallstone disease, diabetes mellitus/impaired glucose tolerance and irritable bowel syndrome, as well as gut microbiota particularities. Overall DB and unbalanced F/B ratios were strongly correlated to abdominal complaints.

Migraine without Aura and Subclinical Atherosclerosis in Young Females: Is Gut Microbiota to Blame?

Background and Objectives: Migraine with aura (MA) could be considered a risk factor for developing atherosclerosis and cardio-vascular events. However, less is known about the relation between migraine without aura (MWA) and atherosclerosis. Our study aimed to assess whether young female migraineurs, with alterations of gut microbiota could associate early atherosclerosis. Materials and Methods: We conducted an exploratory cross-sectional, pilot study concerning 105 consecutive young females having MWA, with recent normal brain scans, that were free of cardio-vascular risk factors, non-smokers, not on oral contraception, not pregnant, and without thyroid or parathyroid diseases, chronic organ failure, cancer, or on probiotic or antibiotic treatment. Consecutive to assessment of gut microbiota, patients were assigned to two groups: dysbiosis positive (n = 45) and dysbiosis negative (n = 60). All study participants underwent clinical examinations with an assessment of migraine severity, body mass index and carotid intima-media thickness (CIMT), as well as laboratory workups. Statistical analysis was performed using a chi-squared test (χ2), a two-tailed t-test and a nonparametric Spearman's correlation test. Results: The dysbiosis positive migraineurs showed a significant increase in CIMT along with several anthropometrical, biological and clinical particularities. Significant positive correlations between dysbiosis and CIMT, glycosylated hemoglobin, migraine severity and duration, tumor necrosis factor-alpha, and body mass index were found. Conclusions: Young female migraineurs with significant alterations of gut microbiota experienced early signs of atherosclerosis and displayed severe migraine disability, as well as multiple biological and clinical particularities.

Migraine in young females with irritable bowel syndrome: still a challenge.

Migraine without aura is frequently reported in female patients with irritable bowel syndrome (IBS), but knowledge about the relationship between these two conditions is still lacking. This study was aimed to explore the particularities of migraine without aura in young female patients with IBS in order to establish a possible link between them. From a cohort of young female patients hospitalized with IBS in the Internal Medicine Department, 30 joined this pilot study, and they were assigned into two groups on the basis of presence or absence of migraine. In this sample, 15 patients have mild to moderate migraine without aura, with a recently taken normal brain scan, and 15 were without migraine. Diseases and conditions not related to migraine and other possible specific female comorbidities were ruled out. Patients undertook a thorough clinical examination in order to assess fibromyalgia (FM) and chronic pelvic pain (CPP), Questionnaires for migraine disability assessment (MIDAS) and generalized anxiety disorder (GAD) were performed. Laboratory testing of blood, urine, and stool were also performed. Optimized lymphocyte proliferation test for food allergy (FA) and a fecal microbiota (microbiological semiquantitative method) for dysbiosis (DB) assessment were performed. Based on the results, migraine-positive group displayed more severe comorbidities: FM (p=0.0002), FA (p=0.0006), CPP (p=0.026), higher scores of anxiety (GAD, p=0.0008), and more severe DB (p=0.0009). We noticed a strong positive correlation between MIDAS and GAD (r=0.83), a good positive correlation between MIDAS and DB (r=0.56), and a moderate positive correlation between MIDAS, FM, and FA (r=0.46 and 0.41). In conclusion, young female patients with IBS and migraine without aura displayed more severe associated issues - anxiety, intestinal DB, FM, FA, and CPP. The severity of migraine correlated well with anxiety range and DB magnitude and moderately with FM and FA.

Nonmotor gastrointestinal disorders in older patients with Parkinson's disease: is there hope?

Despite the fact that nonmotor symptoms (NMS) like gastrointestinal (GI) complaints are frequently reported in Parkinson's disease (PD), no therapeutic guidelines are available. This study aimed to manage some lower GI-NMS in a group of patients with PD. A total of 40 patients (17 males, 23 females; mean age 76.05±2.09 years) were randomly selected for this study. Patients were confirmed to have PD (modified Hoehn-Yars scale: 2.075±0.4) who had undergone levodopa or dopamine agonist treatment. In the non-motor symptoms questionnaire (NMS-Quest), regarding GI complaints, the following were recorded: abdominal pain, bloating, and constipation of mild-to-moderate severity. Laboratory studies, abdominal ultrasound, and upper and lower digestive endoscopies were performed to rule out organic issues. All patients increased their water intake to 2 L/d and alimentary fiber to 20-25 g/d. Twenty patients received trimebutine 200 mg three times daily half an hour before meals. The other 20 patients received probiotics (60 mg per-tablet of two lactic bacteria: Lactobacillus acidophilus and Bifidobacterium infantis), 2×/d, 1 hour after meals for 3 months along with the reassessment of GI complaints. Our results demonstrated that there were significant statistical differences in all assessed symptoms in the first group: 1.55±0.51 vs 0.6±0.5 (P<0.0001) for abdominal pain; 1.6±0.5 vs 0.45±0.51 (P<0.0001) for bloating; and 1.5±0.51 vs 0.85±0.67 (P=0.0014) for constipation with incomplete defecation. The second group displayed statistical differences only for abdominal pain 1.45±0.51 vs 1.05±0.69 (P=0.00432) and bloating 1.4±0.5 vs 0.3±0.47 (P<0.0001). For constipation with incomplete defecation, there was a slight improvement. Thus, there was no significant statistical difference: 1.35±0.49 vs 1.15±0.49 (P=0.2040). In conclusion, lower GI-NMS are frequently present, isolated or associated with other autonomic issues, even before the diagnosis of PD. Treatment with probiotics could improve abdominal pain and bloating as much as with trimebutine, but less for constipation with incomplete evacuation, where trimebutine showed better results.