Gut microbiota and metabolome distinctive features in Parkinson disease: Focus on levodopa and levodopa-carbidopa intrajejunal gel.

BACKGROUND AND PURPOSE: Recent data suggest that imbalances in the composition of the gut microbiota (GM) could exacerbate the progression of Parkinson disease (PD). The effects of levodopa (LD) have been poorly assessed, and those of LD-carbidopa intestinal gel (LCIG) have not been evaluated so far. The aim of this study was to identify the effect of LD and LCIG, in particular, on the GM and metabolome. METHODS: Fecal DNA samples from 107 patients with a clinical diagnosis of PD were analyzed by next-generation sequencing of the V3 and V4 regions of the 16S rRNA gene. PD patients were classified in different groups: patients on LCIG (LCIG group, n = 38) and on LD (LD group, n = 46). We also included a group of patients (n = 23) without antiparkinsonian medicaments (Naïve group). Fecal metabolic extracts were evaluated by gas chromatography mass spectrometry. RESULTS: The multivariate analysis showed a significantly higher abundance in the LCIG group of Enterobacteriaceae, Escherichia, and Serratia compared to the LD group. Compared to the Naïve group, the univariate analysis showed a reduction of Blautia and Lachnospirae in the LD group. Moreover, an increase of Proteobacteria, Enterobacteriaceae, and a reduction of Firmicutes, Lachnospiraceae, and Blautia was found in the LCIG group. No significant difference was found in the multivariate analysis of these comparisons. The LD group and LCIG group were associated with a metabolic profile linked to gut inflammation. CONCLUSIONS: Our results suggest that LD, and mostly LCIG, might significantly influence the microbiota composition and host/bacteria metabolism, acting as stressors in precipitating a specific inflammatory intestinal microenvironment, potentially related to the PD state and progression.

Testimonies and experiences of patients awaiting transplant and transplanted patients in Italy: a survey aiming to understand their needs.

INTRODUCTION AND METHODS: In 2020 the Italian National Transplant Centre (Centro Nazionale Trapianti, Istituto Superiore di Sanità, Rome, Italy) launched two online surveys to explore waitlisted and transplanted patients' needs. RESULTS: The analysis of two-year results shows prevailing feelings of anxiety and discouragement (44.5%) in waitlisted patients. A mere 19.7% expresses feelings of trust and hope. Conversely, in transplanted patients, gratitude (65.7%) predominates. Both transplanted (53.5%) and waitlisted patients (41.5%) worry about organ rejection and complications, SARS-CoV-2 pandemic was an additional concern. The latter report certainty of transplant as their main need (81.3%), followed by psychological support (41.8%) also indicated by 27.9% of transplanted patients, while donor-recipient anonymity is an issue for 31.3% of the transplanted. CONCLUSION: Focusing on the needs and, above all, taking them on, means putting the patient at the centre of care and increasing the chances of a better life despite sufferings and preoccupations.

Role of Maternal Diet in the Risk of Childhood Acute Leukemia: A Systematic Review and Meta-Analysis.

Many studies have investigated the etiology of acute leukemia, one of the most common types of cancer in children; however, there is a lack of clarity regarding preventable risk factors. This systematic review and meta-analysis aimed to summarize the current evidence regarding the role of maternal dietary factors in the development of childhood leukemia. All epidemiological studies published until July 2022 that evaluated maternal dietary risk factors for childhood acute leukemia were identified in two electronic databases (PubMed and Web of Science) without limits of publication year or language. A total of 38 studies (1 prospective cohort study, 34 case-control studies and 3 studies with pooled analysis) were included. The published risk estimates were combined into a meta-analysis, using the Generic Inverse Variance method. The maternal consumption of fruits (two or more daily servings vs. less) was inversely associated with acute lymphoblastic leukemia (odds ratio = 0.71; 95% CI, 0.59-0.86), whereas maternal coffee intake (higher than two cups per day vs. no consumption) was associated with an increased risk of acute lymphoblastic leukemia (odds ratio = 1.45; 95% CI, 1.12-1.89). Despite these findings, more high-quality research from cohort studies and the identification of causal factors are needed to develop evidence-based and cost-effective prevention strategies applicable at the population level. Review Registration: PROSPERO registration no. CRD42019128937.

Early Life Nutrition Factors and Risk of Acute Leukemia in Children: Systematic Review and Meta-Analysis.

Acute leukemia commonly occurs in young children with peak incidence at the age of 2-5 years. However, the etiology is still unclear and many preventable risk factors still deserve to be reviewed. The focus of this systematic review and meta-analysis is to summarize the evidence concerning early life nourishment (breastfeeding, early life diet), neonatal vitamin K administration and the risk of acute leukemia. All epidemiological studies published up to June 2023 and assessing diet-related risk factors for childhood acute leukemia were identified in two electronic databases (PubMed and Web of Science), with no limits on publication year or language. A total of 38 studies (37 case-control studies and 1 study with pooled analysis) were included. The published risk estimates were combined into a meta-analysis using the Generic Inverse Variance method. The current evidence shows that breastfeeding (yes vs. no) has a protective effect against acute lymphoblastic leukemia (odds ratio = 0.85; 95% CI, 0.76-0.94). Evidence related to the role of other studied factors (foods and supplements) is inconclusive. Further research into the potential role of diet in early life and the risk of acute leukemia is needed to develop prevention strategies at population level. Review Registration: PROSPERO registration no. CRD42019128937.

Gut Microbiota Markers and Dietary Habits Associated with Extreme Longevity in Healthy Sardinian Centenarians.

This study was aimed at characterizing the gut microbiota (GM) and its functional profile in two groups of Sardinian subjects with a long healthy life expectancy, overall named Long-Lived Subjects (LLS) [17 centenarians (CENT) and 29 nonagenarians (NON)] by comparing them to 46 healthy younger controls (CTLs). In addition, the contribution of genetics and environmental factors to the GM phenotype was assessed by comparing a subgroup of seven centenarian parents (CPAR) with a paired cohort of centenarians' offspring (COFF). The analysis was performed through Next Generation Sequencing (NGS) of the V3 and V4 hypervariable region of the 16S rRNA gene on the MiSeq Illumina platform. The Verrucomicrobia phylum was identified as the main biomarker in CENT, together with its members Verrucomicrobiaceae, Akkermansia and Akkermansia muciniphila. In NON, the strongest associations concern Actinobacteria phylum, Bifidobacteriaceae and Bifidobacterium, while in CTLs were related to the Bacteroidetes phylum, Bacteroidaceae, Bacteroides and Bacteroides spp. Intestinal microbiota of CPAR and COFF did not differ significantly from each other. Significant correlations between bacterial taxa and clinical and lifestyle data, especially with Mediterranean diet adherence, were observed. We observed a harmonically balanced intestinal community structure in which the increase in taxa associated with intestinal health would limit and counteract the action of potentially pathogenic bacterial species in centenarians. The GM of long-lived individuals showed an intrinsic ability to adapt to changing environmental conditions, as confirmed by functional analysis. The GM analysis of centenarians' offspring suggest that genetics and environmental factors act synergistically as a multifactorial cause in the modulation of GM towards a phenotype similar to that of centenarians, although these findings need to be confirmed by larger study cohorts and by prospective studies.

Association between High Normal TSH Levels and Obesity in Women with Anti-Thyroid Autoantibodies (ATAs).

A positive correlation between Thyroid-Stimulating Hormone (TSH) and Body Mass Index (BMI) has been reported in many studies, but data on this topic remain controversial, especially when TSH values are in the normal range. Moreover, few studies have evaluated the co-existence of thyroid autoimmunity. This study investigated the role of thyroid autoimmunity in the interconnection between TSH, BMI, and waist circumference (WC) in euthyroid patients with overweight or obesity. We enrolled 902 patients (213 males; mean age ± SD: 45 ± 14 years; mean BMI ± SD: 35.8 ± 6.5 kg/m2), with normal serum TSH concentration; anti-thyroid autoantibodies (ATAs) were evaluated in 752 patients (186 males). Patients were divided into four BMI classes, based on WHO criteria, and the relationship between BMI, WC, and TSH was evaluated in the whole sample and compared to ATAs positivity, observed in 235 patients (44 males). No significant difference was found between TSH levels in the BMI classes. A statistically significant correlation between TSH and BMI was found only in ATAs-positive females (N = 191, Spearman rho: 0.149; p-value: 0.040). However, this finding was not confirmed when considering the WC. Our study shows a positive correlation only between TSH and BMI in obese women with positive ATAs, suggesting that in these patients, the high normal levels of TSH could be attributed to a mild thyroid failure with a possible worsening obesity-related effect, and both need a careful evaluation.

Gut microbiota markers associated with obesity and overweight in Italian adults.

In the present study, we characterized the distinctive signatures of the gut microbiota (GM) from overweight/obese patients (OB), and normal-weight controls (NW), both of Sardinian origin. Fecal bacterial composition of 46 OB patients (BMI = 36.6 ± 6.0; F/M = 40/6) was analyzed and compared to that of 46 NW subjects (BMI = 21.6 ± 2.1; F/M = 41/5), matched for sex, age and smoking status, by using 16S rRNA gene sequencing on MiSeq Illumina platform. The gut microbial community of OB patients exhibited a significant decrease in the relative abundance of several Bacteroidetes taxa (i.e. Flavobacteriaceae, Porphyromonadaceae, Sphingobacteriaceae, Flavobacterium, Rikenella spp., Pedobacter spp., Parabacteroides spp., Bacteroides spp.) when compared to NW; instead, several Firmicutes taxa were significantly increased in the same subjects (Lachnospiraceae, Gemellaceae, Paenibacillaceae, Streptococcaceae, Thermicanaceae, Gemella, Mitsuokella, Streptococcus, Acidaminococcus spp., Eubacterium spp., Ruminococcus spp., Megamonas spp., Streptococcus, Thermicanus, Megasphaera spp. and Veillonella spp.). Correlation analysis indicated that body fatness and waist circumference negatively correlated with Bacteroidetes taxa, while Firmicutes taxa positively correlated with body fat and negatively with muscle mass and/or physical activity level. Furthermore, the relative abundance of several bacterial taxa belonging to Enterobacteriaceae family, known to exhibit endotoxic activity, was increased in the OB group compared to NW. The results extend our knowledge on the GM profiles in Italian OB, identifying novel taxa linking obesity and intestine.

Mediterranean diet, lifestyle and quality of life in Sardinian patients affected with Hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa is a chronic inflammatory skin disease with a strong negative impact on physical and psychological health. Obesity, especially visceral adiposity, but also smoking or unhealthy nutritional habits, have been reported to be significantly associated with hidradenitis suppurativa. DESIGN AND METHODS: Case-control study in 35 patients of both sexes affected with hidradenitis suppurativa, and 35 healthy subjects matched for sex, age, and geographic origin (Sardinia, Italy). RESULTS: Several anthropometric measures (body mass index, waist circumference, body composition), lifestyle (Mediterranean diet adherence, and physical activity level), and the perceived physical and mental health status were evaluated in case and controls. Hidradenitis patients showed significantly higher values of body mass index, waist circumference, body composition, fat mass, and lower values of physical and mental health status compared to controls, while both groups showed a similar moderate physical activity level which can be assumed to counteract the negative effects of obesity or poor nutritional pattern in hidradenitis patients. However, none of the evaluated variables were correlated with the severity of the disease, assessed by means of the Hurley stage system or the Sartorius score. Instead, the Sartorius score showed a positive correlation with the duration of hidradenitis, mainly imputable to the diagnostic delay and the consequent long lasting inflammatory status. CONCLUSIONS: Although nutritional factors and lifestyle can be important and modifiable factors in the hidradenitis suppurativa course, the detrimental effect of chronic inflammation and delayed management are clearly prevalent and heavily influence the disease burden.

Clinical Phenotypes of Parkinson's Disease Associate with Distinct Gut Microbiota and Metabolome Enterotypes.

Parkinson's disease (PD) is a clinically heterogenic disorder characterized by distinct clinical entities. Most studies on motor deficits dichotomize PD into tremor dominant (TD) or non-tremor dominant (non-TD) with akinetic-rigid features (AR). Different pathophysiological mechanisms may affect the onset of motor manifestations. Recent studies have suggested that gut microbes may be involved in PD pathogenesis. The aim of this study was to investigate the gut microbiota and metabolome composition in PD patients in relation to TD and non-TD phenotypes. In order to address this issue, gut microbiota and the metabolome structure of PD patients were determined from faecal samples using 16S next generation sequencing and gas chromatography-mass spectrometry approaches. The results showed a reduction in the relative abundance of Lachnospiraceae, Blautia, Coprococcus, Lachnospira, and an increase in Enterobacteriaceae, Escherichia and Serratia linked to non-TD subtypes. Moreover, the levels of important molecules (i.e., nicotinic acid, cadaverine, glucuronic acid) were altered in relation to the severity of phenotype. We hypothesize that the microbiota/metabolome enterotypes associated to non-TD subtypes may favor the development of gut inflammatory environment and gastrointestinal dysfunctions and therefore a more severe α-synucleinopathy. This study adds important information to PD pathogenesis and emphasizes the potential pathophysiological link between gut microbiota/metabolites and PD motor subtypes.

Validity of Accelerometers for the Evaluation of Energy Expenditure in Obese and Overweight Individuals: A Systematic Review.

OBJECTIVE: Even though the validity of accelerometers for the measurement of energy expenditure (EE) has been demonstrated for normal-weight individuals, the applicability of this instrument in obese individuals remains controversial. This review aims to summarize the level of agreement between accelerometers and the gold standards (indirect calorimetry and doubly labelled water) for the measurement of energy expenditure (EE) in obese or overweight individuals. METHODS: The literature search was limited to comparison studies assessing agreement in EE determination between accelerometers and indirect calorimetry (IC) or doubly labelled water (DLW). We searched in PubMed and in Scopus until March 1, 2019. The analysis was restricted to obese or overweight adult individuals. The following descriptive information was extracted for each study: sample size, characteristics of participants (sex, age, BMI, fat mass percentage, any pathological conditions, modality of recruitment in the study, and exclusion criteria), accelerometer description (model, type and body position), and type of gold standard and validity protocol (duration, conditions, and requirements during and before the experiment). Three review authors independently screened the obtained results, and the quality of the selected articles was assessed by the QUADAS-2 tool. RESULTS: We obtained seventeen eligible articles, thirteen of which showed concerns for the applicability section, due to the patient selection. Regarding the accelerometers, nine devices were validated in the included studies with the BodyMedia SenseWear® (SWA) being the most frequently validated. Although correlations between accelerometers and the gold standard were high in some studies, agreement between the two methods was low, as shown by the Bland-Altman plots. CONCLUSIONS: Most accelerometer estimations of EE were inaccurate for obese/overweight subjects, and authors advise to improve the accuracy of algorithms for SWA software, or the predicted equations for estimating EE from other accelerometers.

Impact of a Moderately Hypocaloric Mediterranean Diet on the Gut Microbiota Composition of Italian Obese Patients.

Although it is known that the gut microbiota (GM) can be modulated by diet, the efficacy of specific dietary interventions in determining its composition and diversity in obese patients remains to be ascertained. The present work aims to evaluate the impact of a moderately hypocaloric Mediterranean diet on the GM of obese and overweight patients (OB). The GM of 23 OB patients (F/M = 20/3) was compared before (T0) and after 3 months (T3) of nutritional intervention (NI). Fecal samples were analyzed by Illumina MiSeq sequencing of the 16S rRNA gene. At baseline, GM characterization confirmed typical obesity-associated dysbiosis. After 3 months of NI, patients presented a statistically significant reduction in body weight and fat mass, along with changes in the relative abundance of many microbial patterns. In fact, an increase in the abundance of several Bacteroidetes taxa (i.e., Sphingobacteriaceae, Sphingobacterium, Bacteroides spp., Prevotella stercorea) and a depletion of many Firmicutes taxa (i.e., Lachnospiraceae members, Ruminococcaceae and Ruminococcus, Veillonellaceae, Catenibacterium, Megamonas) were observed. In addition, the phylum Proteobacteria showed an increased abundance, while the genus Sutterella, within the same phylum, decreased after the intervention. Metabolic pathways, predicted by bioinformatic analyses, showed a decrease in membrane transport and cell motility after NI. The present study extends our knowledge of the GM profiles in OB, highlighting the potential benefit of moderate caloric restriction in counteracting the gut dysbiosis.

The Human Microbiome in Relation to Cancer Risk: A Systematic Review of Epidemiologic Studies.

The microbiome has been hypothesized to play a role in cancer development. Because of the diversity of published data, an overview of available epidemiologic evidence linking the microbiome with cancer is now needed. We conducted a systematic review using a tailored search strategy in Medline and EMBASE databases to identify and summarize the current epidemiologic literature on the relationship between the microbiome and different cancer outcomes published until December 2019. We identified 124 eligible articles. The large diversity of parameters used to describe microbial composition made it impossible to harmonize the different studies in a way that would allow meta-analysis, therefore only a qualitative description of results could be performed. Fifty studies reported differences in the gut microbiome between patients with colorectal cancer and various control groups. The most consistent findings were for Fusobacterium, Porphyromonas, and Peptostreptococcus being significantly enriched in fecal and mucosal samples from patients with colorectal cancer. For the oral microbiome, significantly increased and decreased abundance was reported for Fusobacterium and Streptococcus, respectively, in patients with oral cancer compared with controls. Overall, although there was a large amount of evidence for some of these alterations, most require validation in high-quality, preferably prospective, epidemiologic studies.

Gut Microbiota and Metabolome Alterations Associated with Parkinson's Disease.

Parkinson's disease is a neurodegenerative disorder characterized by the accumulation of intracellular aggregates of misfolded alpha-synuclein along the cerebral axis. Several studies report the association between intestinal dysbiosis and Parkinson's disease, although a cause-effect relationship remains to be established. Herein, the gut microbiota composition of 64 Italian patients with Parkinson's disease and 51 controls was determined using a next-generation sequencing approach. A real metagenomics shape based on gas chromatography-mass spectrometry was also investigated. The most significant changes within the Parkinson's disease group highlighted a reduction in bacterial taxa, which are linked to anti-inflammatory/neuroprotective effects, particularly in the Lachnospiraceae family and key members, such as Butyrivibrio, Pseudobutyrivibrio, Coprococcus, and Blautia The direct evaluation of fecal metabolites revealed changes in several classes of metabolites. Changes were seen in lipids (linoleic acid, oleic acid, succinic acid, and sebacic acid), vitamins (pantothenic acid and nicotinic acid), amino acids (isoleucine, leucine, phenylalanine, glutamic acid, and pyroglutamic acid) and other organic compounds (cadaverine, ethanolamine, and hydroxy propionic acid). Most modified metabolites strongly correlated with the abundance of members belonging to the Lachnospiraceae family, suggesting that these gut bacteria correlate with altered metabolism rates in Parkinson's disease.IMPORTANCE To our knowledge, this is one of the few studies thus far that correlates the composition of the gut microbiota with the direct analysis of fecal metabolites in patients with Parkinson's disease. Overall, our data highlight microbiota modifications correlated with numerous fecal metabolites. This suggests that Parkinson's disease is associated with gut dysregulation that involves a synergistic relationship between gut microbes and several bacterial metabolites favoring altered homeostasis. Interestingly, a reduction of short-chain fatty acid (SCFA)-producing bacteria influenced the shape of the metabolomics profile, affecting several metabolites with potential protective effects in the Parkinson group. On the other hand, the extensive impact that intestinal dysbiosis has at the level of numerous metabolic pathways could encourage the identification of specific biomarkers for the diagnosis and treatment of Parkinson's disease, also in light of the effect that specific drugs have on the composition of the intestinal microbiota.