Children, 25 obese and 24 normal weight at 7 years of age
To evaluate whether differences in gut microbiota at an early age precede the development of obesity
Subjects examined at 3, 6, 12, and 24 months and 7 years. Gut microbiota composition at age of 6 and 12 months by FISH, FISH with flow cytometry, and qPCR
↑ Bifidobacteria numbers and ↓ S. aureus at 6 and 12 months of age in children remaining normal wt. ↑ Bacteroides in obese and overweight children during 6 and 12 months versus normal wt. children
↑ numbers of Bifidobacteria and ↓ numbers of S. aureus in infancy may provide protection against overweight and obesity development
3 Obese (OB), 3 normal wt. (NW), and 3 postgastric bypass (GB) patients
To compare the gut microbial community of normal wt., morbidly obese, and postgastric bypass surgery patients
DNA pyrosequencing and amplification by real-time PCR
GB group had a marked increase in Gammaproteobacteria, Enterobacteriaceae, and Fusobacteriaceae and fewer Clostridia. Prevotellaceae (H2 producing) enriched in the OB group compared with the NW group. Methanogenic Archaea (H2 consuming bacteria of the group Archaea) were found ↑ in obese group
Suggests an association between methanogenic Archaea and obesity
Effect of weight loss intervention on the faecal gut microbial composition and immunoglobulin coating bacteria and its relationship to wt. loss
Restricted calories diet and ↑ physical activity for 10 weeks. BMI, BMI -scores before/after intervention. FISH and fluorescent-labelled F(ab′)2 anti-human IgA, IgG, and IgM
Clostridium histolyticum, Eubacterium rectale-Clostridium coccoides groups’ ↓ count with wt. loss. Bacteroides Prevotella ↑ and total faecal energy decreased upon weight loss of >4 kg. IgA coating bacteria ↓ with weight loss of >6 kg
Changes in adolescents’ body wt. are linked to specific gut microbiota and an associated IgA response in obesity after lifestyle interventions
To compare obese and lean individuals’ gut bacterial and immunological biomarkers with blood glucose, lipids, satiety related hormones, and inflammatory markers
Interview for dietary fibre, anthropometry, faecal sample for microbiota diversity using PCR, and inflammatory markers. Blood biochemistry for hormones and inflammatory markers
IL6, CRP, insulin, TG, and leptin ↑ in obese. BCFA and phenolics ↑ in obese faecal samples indicate ↑ bacterial fermentation due to protein rather than carbohydrates. Waist circumference and Bacteroides were −vely correlated while they were +vely correlated with IL-6
↑ phenolics and lactic acid in intestine of obese subjects most probably have an effect on the physiology of systemic inflammatory condition
36 adults; diabetic () and nondiabetic controls ()
To assess the differences between gut microbiota of diabetic and nondiabetic persons
Bacterial composition of faecal samples by real-time PCR and by tag-encoded amplicon pyrosequencing of V4 region of 16S rRNA gene
Bacteroides, Proteobacteria, and Lactobacilli ↑ in diabetics and Firmicutes (clostridium group) were ↑ in nondiabetics. Ratio of Bacteroides Prevotella group to C. coccoides-E. rectale group and Β-Proteobacteria +vely correlated with glucose and E. rectale group −vely correlated with BMI
Reverse F : B ratio in diabetic patients indicates a different bacterial composition in this group. ↑ number of Gram negative bacteria may explain the chronic low-grade inflammation in diabetic patients
18 male and 18 female overweight and obese adolescents
To evaluate the influence of weight loss intervention on the gut microbiota and body wt. of overweight adolescents
Energy restricted diet and ↑ physical activity to all participants. Anthropometric measurements, food diaries, and faecal sample for qPCR
In overall groups and in high wt. loss group (>4 kg); ↑ in Bacteroides fragilis, Lactobacillus group and ↓ in C. coccoides, Bifidobacterium longum, and Bifidobacterium adolescentis. In high versus low wt. loss groups (<2 kg): total bacteria, B. fragilis group and Clostridium leptum group, and Bifidobacterium catenulatum group counts significantly ↑ while levels of C. coccoides group, Lactobacillus group, Bifidobacterium, Bifidobacterium breve, and Bifidobacterium bifidum significantly ↓
Correlation of gut microbiota with body wt. may be sensitive to the lifestyle intervention such as wt. loss to a different extent depending on the composition of gut microbiota of an individual
Obese (), normal weight (), and anorexia nervosa ()
To determine the role of Methanobrevibacter smithii and Lactobacilli in patients with abnormal weights using real-time PCR
Real-time PCR
↓ in the Bacteroidetes community and ↑ Lactobacillus species in obese patients compared to in lean controls or anorexic patients. M. smithii much ↑ in anorexic patients compared to in the lean population
Lactobacilli used as probiotics may be linked to obesity. M. smithii in anorexia nervosa patients may represent an adaptive response to the disease
Overweight and obese mothers () with their infants and nonobese mothers () with their infants
To evaluate the faecal microbiota of infant born to overweight and normal wt. mothers and to find out their relationship with the weight and weight gain of mothers during pregnancy
Faecal sampling of infants, weight of mothers before and during pregnancy. Real-time PCR and FISH with flow cytometry for bacterial composition
Bacteroides and S. aureus ↑ in infants of overweight mothers. Higher weights and maternal BMI related to ↑ concentrations of Bacteroides, Clostridium, and Staphylococcus and ↓ concentrations of the Bifidobacterium group. ↓ counts of Akkermansia muciniphila, Staphylococcus, and Clostridium difficile groups and ↑ number of Bifidobacteria in infants of normal wt. mothers and those with normal pregnancy wt. gains
Lower Bifidobacteria and higher Staph. aureus associated with obesity in children. BMI, weight, and wt. gain of mothers before and during pregnancy affect the gut microbiota composition in infants
12 obese human adults, followed up over a period of 1 year
To investigate the relative abundance of gut microbiota in obese people versus lean individuals
16S rRNA gene sequence library of gut microbiota in obese subjects on wt. reduction diets (low carbohydrate or low fat, )
Gut bacteria are remarkably constant in individuals. Relative proportion of Bacteroidetes ↑ compared with Firmicutes and correlated with percentage of wt. loss
The gut in obesity exerts ecological pressure promoting a higher relative abundance of Firmicutes
To assess the influence of delivery mode, maternal prepregnancy BMI, and child’s early exposure to antibiotics on the child’s risk of overweight
Maternal prepregnancy BMI, delivery mode, and antibiotic administration in infancy. Children followed up at 7 years of age
No significant association of delivery mode with overweight. ↑ risk of overweight and obesity in children, born to normal wt. mothers given antibiotics in first 6 months of life and ↓ risk in children born to overweight mothers
Antibiotics use in early infancy and prepregnancy weight of mother affect tendency of child to become overweight and obese
Healthy Danish infants () at 9, 18, and 36 months of age
Characterisation of gut microbiota of infants at different ages
qPCR, DXA, and bioelectrical impedance analysis for body composition, barcoded food diary for 7 days for dietary analysis
At 9 months: higher Lactobacilli, Bifidobacteria, and Enterobacteria. At 18 months: Firmicutes (particularly C. leptum, E. halii, and Roseburia) and Bacteroidetes ↑ while Bifidobacteria, Lactobacilli, and Enterobacteria ↓ except B. adolescentis. At 36 months: ↑ Firmicutes, Bacteroidetes, and small fraction of Actinobacteria, Proteobacteria, and Verrucomicrobia.↑ in BMI between 9 and 18 months was associated with ↑ Firmicutes
Significant differences occur between 9 and 18 months, and changes at 36 months are independent of breast-feeding at early age. Butyrate producers +vely correlated with BMI might indicate ↑ capability of energy harvest
Overweight and obese children (), healthy lean children () age of 6–16 years
To assess differences in gut microbiota between lean and obese children
Selective plating and qPCR, MALDI-TOF-MS for detailed study of Bacteroides fragilis group. Dietary records for dietary intake
↑ F : B ratio in obese versus lean. ↓ B. vulgatus and ↑ Lactobacilli spp. in obese versus lean. In all groups, Staph. aureus +vely associated with energy intake. Lactobacilli in obese children +vely associated with plasma CRP
To assess differences in gut microbiota associated urinary metabolites between obese and lean and the effect of biliopancreatic or Roux-en-Y surgery on these metabolites
High-resolution proton NMR (1H NMR) spectroscopy
Baseline: ↓ levels of hippurate, xanthine, and trigonelline and ↑ levels of 2-hydroxybutyrate in obese versus lean. Inverse relationship of xanthine with plasma uric acids levels 3 months after surgery: reversal of the above metabolites with wt. loss
Obese phenotype is associated with a peculiar metabotype compared to lean. These metabolic changes are reversed with bariatric surgery
To investigate the effect of prebiotic induced gut microbiota modulation on PUFA derived bacterial metabolites production
Inulin type fructans (oligofructose 50/50) supplementation (16 g/day) for 3 months, qPCR, human intestinal tract chip analysis, circulating fatty acids levels
Treatment with prebiotics did not affect levels of PUFA derived conjugated linoleic and linolenic acids. PUFA derived bacterial metabolites were −vely correlated with total cholesterol, LDL, and HDL, while they were +vely correlated with Bifidobacterium spp., Eubacterium ventriosum, and Lactobacillus spp.
Overweight and obese adults (, age of 21–60 years), lean adults (, age of 18–67 years)
To investigate dietary intakes, faecal SCFA, gut microbiota composition, and physical activity levels in simple obese versus healthy lean adults
3-day food diary, breath methane and hydrogen, faecal SCFA, and qPCR
↑ acetate, propionate, butyrate, valerate, and total SCFA in obese versus lean. No difference in Firmicutes to Bacteroides/Prevotella ratio between lean and obese. ↑ E. coli in lean compared to obese. Irrespective of the group, total faecal SCFA were −vely correlated with Bacteroides/Prevotella and +vely correlated with Firmicutes/Bacteroides ratio
Obese phenotype carries distinct energy harvesting capability compared to lean. However, the evidence is not conclusive due to study limitations
To perform a holistic phylogenetic and functional analysis of the gut microbial communities of the lean and obese microbiome
454 FLX pyrosequencing, Orbitrap MS/MS
Lean microbiome more diverse than obese. High Firmicutes (~95% versus 78%) and low Bacteroidetes (~4% versus ~18%) in obese versus lean. Obese metagenome associated with vitamin B12 and 1,2-propanediol metabolism while lean metagenome associated with B6 metabolism. ↑ butyrate production in obese compared to lean
Lean and obese metagenome and microbiome differ from each other however; both show functional redundancies in terms of proteins expression
To investigate differences in faecal gut microbiota between lean and obese children
qPCR and RFLP, liver function tests
↑ Enterobacteriaceae and ↓ Desulfovibrio and A. muciniphila in obese compared to lean. No difference in Lactobacillus, Bifidobacterium, and Bacteroides fragilis between lean and obese. Serum ALT −vely correlated with Bifidobacterium. No difference in faecal calprotectin between lean and obese
Differences in gut microbiota composition exist at an early age between lean and obese. The study is however cross-sectional. Not controlled for diet and based on PCR
To assess the impact of Roux-en-Y gastric bypass surgery (RYGB) on the gut microbial population and its effect on the genes expression in white adipose tissue (WAT)
454 GS-FLX pyrosequencing of faecal samples at 0, 3, and 6 months after RYGB and dietary assessment
↑ Proteobacteria after RYGB by 37%, ↑ in association between 102 genera and 562 WAT genes. Bifidobacteria andFirmicutes such as Dorea, Lactobacilli, and Blautia ↓ and Bacteroides such as Bacteroidetes and Alistipes and Proteobacteria such as E. coli ↑ after 3 months. About 50% of changes in genes expression were independent of caloric intake. No difference seen between 3 and 6 months
Gut microbiota richness increases after RYGB with changes in association with genes expression in WAT. Further exploration of gut microbiota with weight loss is needed
Evaluation of gut permeability in asymptomatic obese and its relationship with plasma and faecal markers of inflammation and alteration in gut microbiota
Lactulose- mannitol sucralose test for intestinal permeability, blood CRP, and fatty acids. Faecal G + C profiling, calprotectin, and leptin
CRP significantly ↑ in obese compared to nonobese. Faecal fat, calprotectin and leptin, and ARA/EPA not different in both groups. Obese subjects had ↑ in relative abundance bacteria with 23–37% G + C contents in their DNA and ↓ in the relative abundance of those with 40–47% and 57–61% of G + C content. G + C peak values −vely correlated with CRP values
Gut microbiota differ between obese asymptomatic and nonobese. ↑ CRP in asymptomatic obese individuals do not have signs of gut inflammation
Studies suggesting the effect of diet on the gut microbiota and resultant obesity
To investigate the relationship between gut microorganisms, body wt., wt. gain, and various parameters in pregnancy
qPCR, blood glucose, total cholesterol, HDL, TG, LDL, urea, creatinine, uric acid, bilirubin, iron, ferritin, transferrin, folate, and food 24–72 h food diaries for caloric intake
Bifidobacteria and Bacteroides significantly ↑ and E. coli and Staph aureus ↓ in normal wt. Total bacteria especially Staph. aureus +vely correlated with cholesterol. Lactobacillus group −vely correlated with infant birth wt. in women with excess wt. gain
Bifidobacteria and Bacteroides may play a positive role in wt. management of pregnant women and in their metabolic regulation
To examine the relationships between BMI, weight loss, and the major gut microbial groups
Gut microbiota quantification using FISH and quantitative PCR. Dietary intervention with high protein-low carbohydrate ketogenic diet and high protein moderate carbohydrate nonketogenic diet
No difference in total bacteria and Bacteroides between obese and nonobese. No significant relation between BMI, weight loss, diet order, and Bacteroides. ↓ Roseburia-Eubacterium rectale. ↓ Bifidobacteria after 4 weeks of low carbohydrate weight loss diets
No relationship of Bacteroides and Firmicutes ratio at phylum level with obesity
To evaluate the effect of high protein and low fermentable carbohydrate diet on gut microbiota activity and population
Dietary intervention with maintenance, HPMC, and HPLC diets. Bacterial enumeration with FISH and butyrate with GC
Total SCFA ↓ during consumption of the HPMC and HPLC diets. Butyrate was ↓ for the HPLC compared to for the HPMC diet. Butyrate proportion ↓ as carbohydrate supply was ↓. Most abundant bacterial group was Cytophaga-Flavibacterium-Bacteroides group and Clostridial cluster IV. ↓ bacterial count, ↓ Roseburia intestinalis and Eubacterium rectale
Butyrate production and counts of certain bacteria are largely determined by the content of fermentable carbohydrate in the diet
To examine the influence of the precisely controlled diet on the human colonic microbiota population and composition
Intervention with maintenance diet, RS, NSP, low carbohydrate diet, and wheat bran. Chemical analysis of diet composition and digestibility. Real-time qPCR, denaturing gradient gel electrophoresis (DGGE)
Marked interindividual variation was noted. Ruminococcus bromii ↑ with RS diet. Oscillibacter group ↑ on the RS and WL diets. Relatives of Eubacterium rectale and Collinsella aerofaciens ↓ on WL
Different dietary carbohydrates can produce substantial changes in gut bacterial diversity
30 normal weight, 35 overweight, and 33 obese adults
To evaluate the differences in gut bacteria and faecal short chain fatty acids between lean and obese individuals
Faecal samples for quantitative PCR and SCFA analysis
>20% higher SCFA in stools of obese than lean, with ↑ propionate and butyrate. Significantly ↑ Bacteroides in overweight compared to lean but not obese. +ve correlation between BMI and propionate, % propionate, Bifidobacteria and Methanobrevibacter even after correction for the influence of age and gender
Because of controversial results, no specific bacterial group can be attributed to obesity at this stage
31 adult mono- and 23 dizygotic (MZ and DZ) female twins and their mothers ()
To assess how gut microbiome is influenced by the host genotype, external environment, and the extent of host adiposity
UniFrac analysis, and gut microbiota assessed by 16SrRNA pyrosequencing
No significant difference in degree of similarity in gut microbiota of adult MZ versus DZ twin-pairs. ↓ Bacteroides and ↑ Actinobacteria in obese. No significant difference in Firmicutes. Phosphotransferases involved in microbial processing of carbohydrates rich in obese
Genomic profile of microbiota exists at a level of metabolic function and not by a definite set of microbiota
To assess influence of change in nutrient load on gut microbiota of lean and obese individuals and correlation of microbiota with energy harvest from diet
Stool and urine energy content with change in caloric content of diet, culture independent metagenomic studies of microbiota
Nutrient load caused 20% ↑ in Firmicutes and corresponding decrease in Bacteroides in lean subjects with approximately 150 kcal ↑ in energy harvest from diet
Nutrient load affects gut microbiota composition which is also associated with ↑ energy harvest from the diet
Overweight and obese adults (, age of 24–70 yrs) with features of metabolic syndrome
To investigate mechanisms for the effect of high cereal fibre on insulin sensitivity by exploring gut microbiota composition and colonic fermentation
18 weeks of intervention with cereals. GC for SCFA. In vitro fermentation on healthy volunteer faeces with fibres, FISH, and flow cytometry. Euglycemic clamp for insulin sensitivity
No difference in faecal SCFA at 0, 6, and 18 weeks. No differences in SCFA with in vitro fermentation. Roseburia tended to ↓, Clostridium cluster IX ↓ after 6 weeks but not at 18 weeks, and Atopobium ↑ after 18 weeks. Insulin sensitivity improved after 18 weeks
Improvement in insulin sensitivity is not associated with colonic microbiota metabolism and fermentation
To investigate temporal relationship between food intake, gut microbiota, and metabolic and inflammatory phenotype
6-week energy restricted, high protein diet followed by 8 weeks of weight maintenance period, food diaries, and quantitative metagenomics
Gene counts showed bimodal distribution. Patients with low gene count (<480,000 genes) had a tendency towards ↑ LDL, dysmetabolism, insulin resistance, inflammation, and obesity and vice versa for high gene count. Weight loss diet partially ↓ inflammation and improves dysmetabolism but not to full extent
Obesity is associated with lower gene richness which is partially corrected by dietary intervention
Wt.: weight, GB: gastric bypass, OB: obese group, BMI: body mass index, TG: triglycerides, CRP: C-reactive protein, BCFA: branched chain fatty acids, qPCR: quantitative polymerase chain reaction, FISH: florescent in situ hybridization, F : B ratio: Firmicutes to Bacteroides ratio, +vely: positively, −vely: negatively, IL-6: interleukin-6, MALDI-TOF MS: matrix assisted laser desorption/ionization-time of flight mass spectrometry, RFLP: restriction fragment length polymorphism, NMR: nuclear magnetic resonance spectroscopy, ARA/EPA: arachidonic acid/eicosapentaenoic acid, HDL: high density lipoprotein, LDL: low density lipoprotein, HPMC: high protein, medium carbohydrate diet, HPLC: high protein-low carbohydrate diet, RS: resistant starch, NSP: nonstarch polysaccharide, WL: reduced carbohydrate weight loss diet, GC: gas chromatography, SCFA: short chain fatty acids, and TG: triglycerides.
