Associations between bacterial and fungal communities in the human gut microbiota and their implications for nutritional status and body weight.

This study examined the interplay between bacterial and fungal communities in the human gut microbiota, impacting on nutritional status and body weight. Cohorts of 10 participants of healthy weight, 10 overweight, and 10 obese individuals, underwent comprehensive analysis, including dietary, anthropometric, and biochemical evaluations. Microbial composition was studied via gene sequencing of 16S and ITS rDNA regions, revealing bacterial (bacteriota) and fungal (mycobiota) profiles. Bacterial diversity exceeded fungal diversity. Statistically significant differences in bacterial communities were found within healthy-weight, overweight, and obese groups. The Bacillota/Bacteroidota ratio (previously known as the Firmicutes/Bacteroidetes ratio) correlated positively with body mass index. The predominant fungal phyla were Ascomycota and Basidiomycota, with the genera Nakaseomyces, Kazachstania, Kluyveromyces, and Hanseniaspora, inversely correlating with weight gain; while Saccharomyces, Debaryomyces, and Pichia correlated positively with body mass index. Overweight and obese individuals who harbored a higher abundance of Akkermansia muciniphila, demonstrated a favorable lipid and glucose profiles in contrast to those with lower abundance. The overweight group had elevated Candida, positively linked to simple carbohydrate consumption. The study underscores the role of microbial taxa in body mass index and metabolic health. An imbalanced gut bacteriota/mycobiota may contribute to obesity/metabolic disorders, highlighting the significance of investigating both communities.

Change in Urinary Inflammatory Biomarkers and Psychological Health with Gut Microbiome Modulation after Six Months of a Lifestyle Modification Program in Children.

Background: Obesity is a metabolic disorder that negatively impacts the quality of life. Long-term methods such as exercise and low-fat diets can help regulate this health issue, but 93.3 million Americans continue to struggle. Our research investigates if lifestyle changes can affect urinary inflammation markers and psychological aspects through the modification of gut microbiome composition. Methods: Our study included 16 healthy controls with normal BMI as a comparison group and 22 overweight/obese (OW/OB) adolescents. We collected demographic, clinical, psychological, stool, and urine sample data at enrollment and six months after implementing lifestyle modifications. Bacterial genomic data and inflammatory markers in these samples were analyzed. Results: The lifestyle interventions were associated with decreased inflammation and enhanced mental health among overweight teens. We observed differences in bacterial community compositions between healthy participants and those who underwent treatment, including exercise and dietary habit adjustments, although there was no significant change in bacterial species richness. Mental health correlated with gut microbiota compositions without any demographic influences. The research also uncovered connections between inflammatory markers, psychological factors, and gut microbiota phyla through carbohydrate metabolism alterations. Conclusion: Our findings demonstrate that lifestyle modifications are associated with improved mental health and a reduction in inflammation in overweight adolescents by adjusting the gut microbiota composition.

Effect of a 12-Week Polyphenol Rutin Intervention on Markers of Pancreatic ß-Cell Function and Gut Microbiota in Adults with Overweight without Diabetes.

Supplementation with prebiotic polyphenol rutin is a potential dietary therapy for type 2 diabetes prevention in adults with obesity, based on previous glycaemic improvement in transgenic mouse models. Gut microbiota are hypothesised to underpin these effects. We investigated the effect of rutin supplementation on pancreatic ß-cell function measured as C-peptide/glucose ratio, and 16S rRNA gene-based gut microbiota profiles, in a cohort of individuals with overweight plus normoglycaemia or prediabetes. Eighty-seven participants were enrolled, aged 18-65 years with BMI of 23-35 kg/m2. This was a 12-week double-blind randomised controlled trial (RCT), with 3 treatments comprising (i) placebo control, (ii) 500 mg/day encapsulated rutin, and (iii) 500 mg/day rutin-supplemented yoghurt. A 2-h oral glucose tolerance test (OGTT) was performed at baseline and at the end of the trial, with faecal samples also collected. Compliance with treatment was high (~90%), but rutin in both capsule and dietary format did not alter pancreatic ß-cell response to OGTT over 12 weeks. Gut bacterial community composition also did not significantly change, with Firmicutes dominating irrespective of treatment. Fasting plasma glucose negatively correlated with the abundance of the butyrate producer Roseburia inulinivorans, known for its anti-inflammatory capacity. This is the first RCT to investigate postprandial pancreatic ß-cell function in response to rutin supplementation.

Compliance with Nutritional Recommendations and Gut Microbiota Profile in Galician Overweight/Obese and Normal-Weight Individuals.

Different research studies have identified specific groups or certain dietary compounds as the onset and progression of obesity and suggested that gut microbiota is a mediator between these compounds and the inflammation associated with pathology. In this study, the objective was to evaluate the dietary intake of 108 overweight (OW), obese (OB), and normal-weight (NW) individuals and to analyze their gut microbiota profile to determine changes and associations with Body Mass Index (BMI) and diet. When individuals were compared by BMI, significant differences in fiber and monounsaturated fatty acids (MUFAs) intake were observed, showing higher adequacy for the NW group. The analysis of gut microbiota showed statistical differences for 18 ASVs; Anaerostipes and Faecalibacterium decreased in the OW/OB group, whereas the genus Oscillospira increased; the genus was also found in the LEFSe analysis as a biomarker for OW/OB. Roseburia faecis was found in a significantly higher proportion of NW individuals and identified as a biomarker for the NW group. Correlation analysis showed that adequation to nutritional recommendation for fiber indicated a higher abundance of Prevotella copri, linearly correlated with F. prausnitzii, Bacteroides caccae, and R. faecis. The same correlation was found for the adequation for MUFAs, with these bacteria being more abundant when the intake was adjusted to or below the recommendations.

Gut microbiome profiles may be related to atypical antipsychotic associated overweight in Asian children with psychiatric disorder: a preliminary study.

Objective: Atypical antipsychotics (APs) modify the gut microbiome, and weight gain in response to AP could be mediated by the gut microbiome. Thus, the present study aimed to explore the changes in the gut bacterial microbiome in AP-exposed children with obesity. Methods: To rule out the confounder of AP indication, the gut bacterial microbiome was compared between healthy controls (Con) and AP-exposed individuals with overweight (APO) or normal weight (APN). Fifty-seven AP-treated outpatients (21 APO and 36 APN) and 25 Con were included in this cross-sectional microbiota study. Results: AP users, regardless of body mass index, exhibited decreased microbial richness and diversity and a distinct metagenomic composition compared to the Con. Although no differences in the microbiota structure were observed between APO and APN groups, the APO group was characterised by a higher abundance of Megamonas and Lachnospira. Additionally, the differences in the microbial functions were observed between APO and APN groups. Conclusions: The gut bacterial microbiota of APO children revealed taxonomic and functional differences compared to Con and APN. Further studies are needed to verify these findings and to explore the temporal and causal relationships between these variables.

Physical activity-induced alterations of the gut microbiota are BMI dependent.

Physical inactivity is one of the leading causes of chronic metabolic disease including obesity. Increasing physical activity (PA) has been shown to improve cardiometabolic and musculoskeletal health and to be associated with a distinct gut microbiota composition in trained athletes. However, the impact of PA on the gut microbiota is inconclusive for individuals performing PA in their day-to-day life. This study examined the role of PA and hand-grip strength on gut microbiome composition in middle-aged adults (40-65 years, n = 350) with normal (18.5-24.9 kg/m2 ) and overweight (25-29.9 kg/m2 ) body mass index (BMI). PA was recorded using the International Physical Activity Questionnaire, and hand-grip strength was measured using a dynamometer. Serum samples were assessed for lipidomics while DNA was extracted from fecal samples for microbiome analysis. Overweight participants showed a higher concentration of triacylglycerols, and lower concentrations of cholesteryl esters, sphingomyelin, and lyso-phosphotidylcholine lipids (p < .05) compared with those with normal BMI. Additionally, overweight participants had a lower abundance of the Oscillibacter genus (p < .05). The impact of PA duration on the gut microbiome was BMI dependent. In normal but not overweight participants, high PA duration showed greater relative abundance of commensal taxa such as Actinobacteria and Proteobacteria phyla, as well as Collinsella and Prevotella genera (p < .05). Furthermore, in males with normal BMI, a stronger grip strength was associated with a higher relative abundance of Faecalibacterium and F. prausnitzii (p < .05) compared with lower grip strength. Taken together, data suggest that BMI plays a significant role in modeling PA-induced changes in gut microbiota.

Cytokine and microbiota profiles in obesity-related hypertension patients.

Background: Systemic arterial hypertension is linked to a heightened risk of cardiovascular diseases on a global scale. In Mexico, nearly half of adults in vulnerable conditions experience hypertension. Imbalance in the oral and intestinal microbiota composition has been observed in patients with hypertension, documented by a decrease of bacteria producing short-chain fatty acids, which play a critical role in blood pressure regulation. Aim: To examine the cytokines' profile and assess the characteristics of oral and gut microbiota in obesity-related hypertension in Mexican patients. Methods: A cross-sectional, observational, and analytical study was carried out. Twenty-two patients were categorized by their body mass index (BMI) as overweight and obese, and the diagnosis of primary hypertension. DNA from supragingival dental plaque and feces samples was used to carry out 16S rRNA sequencing. Additionally, 13 cytokines were quantified. Results: In the oral microbiota, Kluyvera was found to be significantly enriched in obese compared to overweight patients. Instead, the gut microbiota was dominated by Firmicutes. However, the correlation between certain genera and proinflammatory cytokines was noted. Conclusion: This exploratory study provides insights into the complex relationship between the oral and gut microbiota and their association with systemic inflammation in obesity-related hypertension.

Precision Nutrition Model Predicts Glucose Control of Overweight Females Following the Consumption of Potatoes High in Resistant Starch.

Individual glycemic responses following dietary intake result from complex physiological processes, and can be influenced by physical properties of foods, such as increased resistant starch (RS) from starch retrogradation. Predictive equations are needed to provide personalized dietary recommendations to reduce chronic disease development. Therefore, a precision nutrition model predicting the postprandial glucose response (PPGR) in overweight women following the consumption of potatoes was formulated. Thirty overweight women participated in this randomized crossover trial. Participants consumed 250 g of hot (9.2 g RS) or cold (13.7 g RS) potatoes on two separate occasions. Baseline characteristics included demographics, 10-day dietary records, body composition, and the relative abundance (RA) and α-diversity of gut microbiota. Elastic net regression using 5-fold cross-validation predicted PPGR after potato intake. Most participants (70%) had a favorable PPGR to the cold potato. The model explained 32.2% of the variance in PPGR with the equation: 547.65 × (0 [if cold, high-RS potato], ×1, if hot, low-RS potato]) + (BMI [kg/m2] × 40.66)-(insoluble fiber [g] × 49.35) + (Bacteroides [RA] × 8.69)-(Faecalibacterium [RA] × 73.49)-(Parabacteroides [RA] × 42.08) + (α-diversity × 110.87) + 292.52. This model improves the understanding of baseline characteristics that explain interpersonal variation in PPGR following potato intake and offers a tool to optimize dietary recommendations for a commonly consumed food.

Gut Microbiota Diversity and Overweight/Obesity in Infancy: Results from a Nested Case-control Study.

OBJECTIVE: Childhood obesity is a major health concern worldwide. Previous studies have explored the relationship between obesity and gut microbiota. However, the results from such studies remain contradictory. METHODS: In the present nested case-control study, based on a twin birth cohort study, the relationship between gut microbiota diversity and overweight/obesity in 1- and 6-month-old infants was explored. Twins were enrolled when one child had normal weight and the other child was overweight/obese at six months old. For both infants, stool samples were collected at 1 and 6 months of age. Finally, 12 twins were enrolled in the study. The gut microbiota was identified by 16S rRNA gene sequencing in the V3-V4 area. Six of the twins were monozygotic. RESULTS: The results revealed that the microbiota communities of monozygotic twins were similar to those of dizygotic twins. The relative abundance (RA) of microbiota of 1-month-old twins was significantly higher than that of 6-month-old twins. However, the microbiota diversity of 1-month-old twins was significantly lower than that of 6-month-old twins. In addition, 6-month-old twins had significantly higher RA levels of Bifidobacterium and Lachnospiracea incertae sedis than 1-month-old twins. The 6-month-old group had significantly lower RA levels of Veillonella, Klebsiella, Akkermansia, Streptococcus, or Staphylococcus than the 1-month-old group. At six months, the RA level of Clostridium sensu stricto was higher in the overweight/obesity group than the normal-weight group. CONCLUSION: These findings imply that changes in gut microbiota diversity during infancy may contribute to the development of obesity in early infancy.

Fiber mixture-specific effect on distal colonic fermentation and metabolic health in lean but not in prediabetic men.

Infusions of the short-chain fatty acid (SCFA) acetate in the distal colon improved metabolic parameters in men. Here, we hypothesized that combining rapidly and slowly fermentable fibers will enhance distal colonic acetate production and improve metabolic health. In vitro cultivation studies in a validated model of the colon were used to identify fiber mixtures that yielded high distal colonic acetate production. Subsequently, in two randomized crossover studies, lean and prediabetic overweight/obese men were included. In one study, participants received supplements of either long-chain inulin+resistant starch (INU+RS), INU or maltodextrin (PLA) the day prior to a clinical investigation day (CID). The second trial studied beta glucan+RS (BG+RS) versus BG and PLA. During each CID, breath hydrogen, indirect calorimetry, plasma metabolites/hormones were assessed during fasting and postprandial conditions. Additionally, fecal microbiota composition and SCFA were determined. In prediabetic men, INU+RS increased plasma acetate compared to INU or PLA (P < .05), but did not affect metabolic parameters. In lean men, INU+RS increased breath hydrogen and fasting plasma butyrate, which was accompanied by increased energy expenditure, carbohydrate oxidation and PYY and decreased postprandial glucose concentrations (all P < .05) compared to PLA. BG+RS increased plasma butyrate compared to PLA (P < .05) in prediabetic individuals, but did not affect other fermentation/metabolic markers in both phenotypes. Fiber-induced shifts in fecal microbiota were individual-specific and more pronounced with INU+RS versus BG+RS. Administration of INU+RS (not BG+RS) the day prior to investigation improved metabolic parameters in lean but not in prediabetic individuals, demonstrating that effects were phenotype- and fiber-specific. Further research should study whether longer-term supplementation periods are required to elicit beneficial metabolic health in prediabetic individuals. Trial registration numbers: Clinical trial No. NCT03711383 (Inulin study) and Clinical trial No. NCT03714646 (Beta glucan study).

Effects of Probiotics and Synbiotics on Weight Loss in Subjects with Overweight or Obesity: A Systematic Review.

Intestinal microbiota has been shown to be a potential determining factor in the development of obesity. The objective of this systematic review is to collect and learn, based on the latest available evidence, the effect of the use of probiotics and synbiotics in randomized clinical trials on weight loss in people with overweight and obesity. A search for articles was carried out in PubMed, Web of science and Scopus until September 2021, using search strategies that included the terms "obesity", "overweight", "probiotic", "synbiotic", "Lactobacillus", "Bifidobacterium" and "weight loss". Of the 185 articles found, only 27 complied with the selection criteria and were analyzed in the review, of which 23 observed positive effects on weight loss. The intake of probiotics or synbiotics could lead to significant weight reductions, either maintaining habitual lifestyle habits or in combination with energy restriction and/or increased physical activity for an average of 12 weeks. Specific strains belonging to the genus Lactobacillus and Bifidobacterium were the most used and those that showed the best results in reducing body weight. Both probiotics and synbiotics have the potential to help in weight loss in overweight and obese populations.

Effects of probiotics on body adiposity and cardiovascular risk markers in individuals with overweight and obesity: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND & AIMS: Evidence suggests that gut microbiota is a potential factor in the pathophysiology of both obesity and related metabolic disorders. While individual randomized controlled trials (RCTs) have evaluated the effects of probiotics on adiposity and cardiovascular disease (CVD) risk factors in subjects with overweight and obesity, the results are inconsistent. Thus, this systematic review and meta-analysis aimed to evaluate the effects of probiotic supplementation on body weight, body adiposity and CVD risk markers in overweight and obese subjects. METHODS: A systematic search for RCTs published up to December 2020 was conducted in MEDLINE (via PubMed), EMBASE, Scopus and LILACS. Meta-analysis using a random-effects model was chosen to analyze the impact of combined trials. RESULTS: Twenty-six RCTs (n = 1720) were included. Data pooling showed a significant effect of probiotics in reducing body weight (MD:-0.70 kg; 95%CI:-1.04,-0.35 kg; P < 0.0001), body mass index (BMI) (MD:-0.24 kg/m2; 95%CI:-0.35,-0.12 kg/m2; P = 0.0001), waist circumference (WC) (MD:-1.13 cm; 95%CI:-1.54,-0.73 cm; P < 0.0001), fat mass (MD:-0.71 kg; 95%CI:-1.10,-0.32 kg; P = 0.0004), tumor necrosis factor-α (MD:-0.16 pg/ml; 95%CI:-0.24,-0.08 pg/ml; P = 0.0001), insulin (MD:-0.85mcU/ml; 95%CI:-1.50,-0.21mcU/ml; P = 0.010), total cholesterol (MD:-0.16 mmol/l; 95%CI:-0.26,-0.05 mmol/l; P = 0.003) and LDL (MD:-0.09 mmol/l; 95%CI:-0.16,-0.03 mmol/l; P = 0.006) compared with control groups. There was a significant decrease in body weight, BMI and WC in studies using both single and multi-bacterial species. Decreases in body adiposity parameters were only observed in studies using a probiotic dose of ≥ 1010 CFU and for ≥8 weeks duration. CONCLUSIONS: The present meta-analysis suggests that probiotics consumption may be helpful for improving body weight, body adiposity and some CVD risk markers in individuals with overweight and obesity. The review was registered on PROSPERO (International prospective register of systematic reviews): CRD42020183136.

Gut Microbiota Profile and Its Association with Clinical Variables and Dietary Intake in Overweight/Obese and Lean Subjects: A Cross-Sectional Study.

We aimed to differentiate gut microbiota composition of overweight/obese and lean subjects and to determine its association with clinical variables and dietary intake. A cross-sectional study was performed with 96 overweight/obese subjects and 32 lean subjects. Anthropometric parameters were positively associated with Collinsella aerofaciens, Dorea formicigenerans and Dorea longicatena, which had higher abundance the overweight/obese subjects. Moreover, different genera of Lachnospiraceae were negatively associated with body fat, LDL and total cholesterol. Saturated fatty acids (SFAs) were negatively associated with the genus Intestinimonas, a biomarker of the overweight/obese group, whereas SFAs were positively associated with Roseburia, a biomarker for the lean group. In conclusion, Dorea formicigenerans, Dorea longicatena and Collinsella aerofaciens could be considered obesity biomarkers, Lachnospiraceae is associated with lipid cardiovascular risk factors. SFAs exhibited opposite association profiles with butyrate-producing bacteria depending on the BMI. Thus, the relationship between diet and microbiota opens new tools for the management of obesity.

Evaluating microbiome-directed fibre snacks in gnotobiotic mice and humans.

Changing food preferences brought about by westernization that have deleterious health effects1,2-combined with myriad forces that are contributing to increased food insecurity-are catalysing efforts to identify more nutritious and affordable foods3. Consumption of dietary fibre can help to prevent cardiovascular disease, type 2 diabetes and obesity4-6. A substantial number of reports have explored the effects of dietary fibre on the gut microbial community7-9. However, the microbiome is complex, dynamic and exhibits considerable intra- and interpersonal variation in its composition and functions. The large number of potential interactions between the components of the microbiome makes it challenging to define the mechanisms by which food ingredients affect community properties. Here we address the question of how foods containing different fibre preparations can be designed to alter functions associated with specific components of the microbiome. Because a marked increase in snack consumption is associated with westernization, we formulated snack prototypes using plant fibres from different sustainable sources that targeted distinct features of the gut microbiomes of individuals with obesity when transplanted into gnotobiotic mice. We used these snacks to supplement controlled diets that were consumed by adult individuals with obesity or who were overweight. Fibre-specific changes in their microbiomes were linked to changes in their plasma proteomes indicative of an altered physiological state.

Low-carbohydrate high-fat weight reduction diet induces changes in human gut microbiota.

Obesity has become a major public health problem in recent decades. More effective interventions may result from a better understanding of microbiota alterations caused by weight loss and diet. Our objectives were (a) to calculate the fiber composition of a specially designed low-calorie weight loss diet (WLD), and (b) to evaluate changes in the composition of gut microbiota and improvements in health characteristics during WLD. A total of 19 overweight/obese participants were assigned to 20%-40% reduced calories low-carbohydrate high-fat diet for four weeks. Protein and fat content in the composed diet was 1.5 times higher compared to that in the average diet of the normal weight reference group, while carbohydrate content was 2 times lower. Food consumption data were obtained from the assigned meals. Microbial composition was analyzed before and after WLD intervention from two sequential samples by 16S rRNA gene sequencing. During WLD, body mass index (BMI) was reduced on average 2.5 ± 0.6 kg/m2 and stool frequency was normalized. The assigned diet induced significant changes in fecal microbiota. The abundance of bile-resistant bacteria (Alistipes, Odoribacter splanchnicus), Ruminococcus bicirculans, Butyricimonas, and Enterobacteriaceae increased. Importantly, abundance of bacteria often associated with inflammation such as Collinsella and Dorea decreased in parallel with a decrease in BMI. Also, we observed a reduction in bifidobacteria, which can be attributed to the relatively low consumption of grains. In conclusion, weight loss results in significant alteration of the microbial community structure.

The Efficacy of Short-Term Weight Loss Programs and Consumption of Natural Probiotic Bryndza Cheese on Gut Microbiota Composition in Women.

Weight loss interventions with probiotics have favourable effects on gut microbiota composition and derived metabolites. However, little is known about whether the consumption of natural probiotics, such as Bryndza cheeses, brings similar benefits. The purpose of the study was to find the effect of short-term weight loss programs and Bryndza cheese consumption on the structure of the gut microbiota, microbiota-derived metabolites and body composition in middle-aged women. We conducted a randomised controlled intervention study. Twenty-two female participants with a body fat percentage ≥25% underwent a short weight loss program (4 weeks). Subjects were randomised to either the control or intervention group according to diet. The intervention group comprised 13 participants, whose diet contained 30 g of "Bryndza" cheese daily (WLPB). The control group comprised nine participants without the regular consumption of Bryndza cheese (WLP) in their diet. Both interventions lead to a significant and favourable change of BMI, body fat, waist circumference and muscle mass. Moreover, the relative abundance of Erysipelotrichales significantly increased in both groups. However, the relative abundance of lactic acid bacteria (Lactobacillales, Streptococcaceae, Lactococcus and Streptococcus) significantly increased only in the WLPB group. Furthermore, short-chain fatty acid producers Phascolarctobacterium and Butyricimonas increased significantly in the WLPB group. A short-term weight loss program combined with Bryndza cheese consumption improves body composition and increases the abundance of lactic acid bacteria and short-chain fatty acid producers in middle-aged women.

Gut microbial differences in breast and prostate cancer cases from two randomised controlled trials compared to matched cancer-free controls.

Implicated in several chronic diseases, the gastrointestinal microbiome is hypothesised to influence carcinogenesis. We compared faecal microbiota of newly diagnosed treatment-naïve overweight and obese cancer patients and matched controls. Cases were enrolled in presurgical weight-loss trials for breast (NCT02224807) and prostate (NCT01886677) cancers and had a body mass index (BMI) ≥25 kg/m2. Cancer-free controls were matched 1:1 by age (±5 years), race, gender, and BMI (±5 kg/m2). All participants provided faecal samples; isolated bacterial DNA were PCR amplified at the V4 region of the 16S rRNA gene and analysed using the QIIME pipeline. Tests compared cases versus controls, then separately by gender. Microbial alpha-diversity and beta-diversity were assessed, and relative abundance of Operational Taxonomic Units (OTU's) were compared at the genus level, with false discovery rate (FDR) correction. 22 overweight and obese cancer patients were matched with 22 cancer-free controls, with an average BMI of 30.5±4.3 kg/m2, age 54.4±5.3 years, and 54.5% were black. Fourteen matches were made between breast cancer cases and healthy female controls, and 8 matches were made with prostate cancer cases and healthy male controls. Comparison of all cases and controls revealed no differences in alpha diversity, though prostate cancer patients had higher Chao1 (P=0.006) and Observed Species (P=0.036) than cancer-free males. Beta-diversity metrics were significantly different between cases and controls (P<0.03 for all tests in whole sample and in men), though only unweighted Unifrac was different in women (P=0.005). Kruskal Wallis tests indicated significant differences among 16 genera in all matches, 9 in female, and 51 in male. This study suggests the faecal microbiota of treatment-naive breast and prostate cancer patients differs from controls, though larger samples are needed to substantiate these findings. Trial registration: NIH Clinical Trials, NCT01886677, NCT02224807, registered 26 June 2013, 25 Aug 2014 (respectively) - retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT01886677; https://clinicaltrials.gov/ct2/show/NCT02224807.

Fecal Microbiota Transplantation from Overweight or Obese Donors in Cachectic Patients with Advanced Gastroesophageal Cancer: A Randomized, Double-blind, Placebo-Controlled, Phase II Study.

PURPOSE: Cachexia is a multifactorial syndrome, associated with poor survival in patients with cancer, and is influenced by the gut microbiota. We investigated the effects of fecal microbiota transplantation (FMT) on cachexia and treatment response in patients with advanced gastroesophageal cancer. EXPERIMENTAL DESIGN: In a double-blind randomized placebo-controlled trial performed in the Amsterdam University Medical Center, we assigned 24 cachectic patients with metastatic HER2-negative gastroesophageal cancer to either allogenic FMT (healthy obese donor) or autologous FMT, prior to palliative chemotherapy (capecitabine and oxaliplatin). Primary objective was to assess the effect of allogenic FMT on satiety. Secondary outcomes were other features of cachexia, along with disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and toxicity. Finally, exploratory analyses were performed on the effect of FMT on gut microbiota composition (metagenomic sequencing) and metabolites (untargeted metabolomics). RESULTS: Allogenic FMT did not improve any of the cachexia outcomes. Patients in the allogenic group (n = 12) had a higher DCR at 12 weeks (P = 0.035) compared with the autologous group (n = 12), longer median OS of 365 versus 227 days [HR = 0.38; 95% confidence interval (CI), 0.14-1.05; P = 0.057] and PFS of 204 versus 93 days (HR = 0.50; 95% CI, 0.21-1.20; P = 0.092). Patients in the allogenic group showed a significant shift in fecal microbiota composition after FMT (P = 0.010) indicating proper engraftment of the donor microbiota. CONCLUSIONS: FMT from a healthy obese donor prior to first-line chemotherapy did not affect cachexia, but may have improved response and survival in patients with metastatic gastroesophageal cancer. These results provide a rational for larger FMT trials.

The intestinal mycobiota and its relationship with overweight, obesity and nutritional aspects.

BACKGROUND: The fungal community of the gastrointestinal tract has recently become of interest, and knowledge of its relationship with the development of obesity is scarce. The present study aimed to evaluate the cultivable fungal fraction from the microbiota and to analyze its relationship with obesity. METHODS: Samples were taken from 99 participants with normal weight, overweight and obesity (n = 31, 34 and 34, respectively) and were cultivated in selective medium, and the cultivable yeasts were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Anthropometric and biochemical measures were also evaluated. RESULTS: Eutrophic, overweight and obese groups presented concentrations of 1.6, 2.16 and 2.19 log10  colony-forming units g-1 yeast, respectively. Ascomycota and Basidiomycota were the two identified phyla. At the genus level, Candida spp. showed a relatively high prevalence, and 10 different species were detected: Candida glabrata, Candida orthopsilosis, Candida lambica, Candida kefyr, Candida albicans, Candida krusei, Candida valida, Candida parapsilosis, Candida utilis and Candida humilis (with relative abundances of 71.72%, 5.05%, 21.21%, 6.06%, 29.29%, 27.27%, 8.08%, 16.16%, 1.01% and 2.02%, respectively). CONCLUSIONS: The obese group presented a higher prevalence of Candida albicans. Furthermore, Candida albicans, Candida kefyr and Rhodotorula mucilaginosa showed a high positive correlation with obesity, weight gain and fat mass and showed a negative correlation with high-density lipoprotein and lean mass, parameters related to weight loss.

Almond consumption affects fecal microbiota composition, stool pH, and stool moisture in overweight and obese adults with elevated fasting blood glucose: A randomized controlled trial.

Regular almond consumption has been shown to improve body weight management, lipid profile and blood glucose control. We hypothesized that almond consumption would alter fecal microbiota composition, including increased abundance and activity of potentially beneficial bacterial taxa in adults who are overweight and obese with elevated fasting blood glucose. A total of 69 adults who were overweight or obese with an elevated plasma glucose (age: 60.8 ± 7.4, BMI ≥27 kg/m2, fasting plasma glucose ≥5.6 to <7.0 mmol/L) were randomized to daily consumption of either 2 servings of almonds (AS:56 g/day) or an isocaloric, high carbohydrate biscuit snack for 8 weeks. AS but not biscuit snack experienced significant changes in microbiota composition (P= .011) and increases in bacterial richness, evenness, and diversity (P< .01). Increases in both the relative and absolute abundance of operational taxonomic units in the Ruminococcaceae family, including Ruminiclostridium (false discovery rate P = .002), Ruminococcaceae NK4A214 (P = .002) and Ruminococcaceae UCG-003 (P = .002) were the principal drivers of microbiota-level changes. No changes in fecal short chain fatty acid levels, or in the carriage of the gene encoding butyryl-CoA:acetate CoA-transferase (an enzyme involved in butyrate synthesis) occurred. Almond consumption was not associated with reduced gut permeability, but fecal pH (P= .0006) and moisture content (P = .027) decreased significantly in AS when compared to BS. Regular almond consumption increased the abundance of potentially beneficial ruminococci in the fecal microbiota in individuals with elevated blood glucose. However, fecal short-chain fatty acid levels remained unaltered and the capacity for such microbiological effects to precipitate host benefit is not known.