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Review
. 2014 May;3(3):44-57.
doi: 10.7453/gahmj.2014.018.

The role of the gut microbiome in the pathogenesis and treatment of obesity

Francis Okeke  1 , Bani Chander Roland  1 , Gerard E Mullin  1
Affiliations
Review

The role of the gut microbiome in the pathogenesis and treatment of obesity

Francis Okeke et al. Glob Adv Health Med. 2014 May.
No abstract available

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Figures

Figure 1
Figure 1
Meta-analysis of the obesity-associated gut microbiota alterations at the phylum level. Meta-analysis was performed with the comprehensive meta-analysis software version 2 (Biostat, Englewood, New Jersey). Each line represents a comparison between an obese group (right) and a control group (left). The first reported alteration was a decrease in the relative proportion of Bacteroidetes (percentage decrease) represented by a deviation of the square (standardized difference in the means) to the left. The size of the square represents the relative weight of each comparison (random model). The length of the horizontal line represents the 95% CI and the diamond represents the summarized effect. The presence of a square to the right and left of the midline means studies with conflicting results corresponding to a substantial heterogeneity (12 >50%). Here, the only reproducible and significant alteration at the phylum level is the decrease in the absolute number of sequences of Firmicutes in obese subjects. Relative count of Bacteroidetes (n=4; SDM=−0.51; 95% CI=-1.7-0.67; P=.40 [I2=81%]); absolute count of Bacteroidetes (n=4; SDM=-0.07; 95% CI=-0.78-0.65; P=.86 [I2=85]); relative count of Firmicutes (n=3; SDM=0.88; 95% CI=-0.21-1.97; P=.11 [I2=79%]); absolute count of Firmicutes (n=3; SDM=-0.43; 95% CI=-0.72 to -0.15; P=.003 [I2=0%]). Abbreviations: FCM, Flow cytometry; Ow, Overweight; qPCR, Quantitative PCR; SDM, standardized difference in the means. Reproduced with permission from Angelakis E, Armougom F, Million M, et al. The relationship between gut microbiota and weight gain in humans. Future Microbiol. 2012;7(1):91-109.66
Figure 2
Figure 2
Population of bacteria found to increase in obese and lean individuals. Summary of evidence for consistent changes in the gut microbiome of obese human subjects versus lean individuals. Reproduced with permission from Angelakis E, Armougom F, Million M, et al. The relationship between gut microbiota and weight gain in humans. Future Microbiol. 2012 Jan;7(1):91-109.
Figure 3
Figure 3
Meta-analysis of the obesity-associated gut microbiota alterations at the genus level for Bifidobacteria and Lactobacilli comparing the absolute number of sequences generated by genus-specific quantitative PCR. For Bifidobacteria, a consistent difference was found by our meta-analysis between 159 obese subjects and 189 controls from six published studies showing that the digestive microbiota of the obese group was significantly depleted in Bifidobacteria. Low heterogeneity (I2=17%) shows that this result is very robust. Additional tests have shown that there was no small studies bias (Egger's regression intercept test, P=.92; no change after Duval and Tweedie's trim and fill). For Lactobacilli, no consistent and significant summary effect was found comparing 127 obese subjects and 110 controls from three studies. Bifidobacterium spp (n=6; SDM=-0.45; 95% CI=-0.69 to -0.20; P<.001 [I2=17%]); Lactobacillus spp (n=3; SDM=0.29; 95% CI=-0.31-0.90; P=.34 [I2=80%]). Abbreviations: Ow: overweight; SDM, atandardized difference in the means. Reproduced with permission from Angelakis E, Armougom F, Million M, et al. The relationship between gut microbiota and weight gain in humans. Future Microbiol. 2012 Jan;7(1):91-109.
Figure 4
Figure 4
The gut microbiome has a regulatory function on host energy metabolism. By breaking down nondigestible polysaccharides, gut microorganisms produce monosaccharides and short-chain fatty acids (SCFAs). SCFAs bind to GPR 41/43 receptors and stimulate peptide YY (PYY) production, which inhibits gut motility and allows gut microbes to digest more polysaccharides. Gut microbes also regulate energy metabolism by reducing the expression of fasting-induced adipocyte factor (Fiaf) from gut epithelial cells. Suppressed Fiaf release results in the degradation of lipoproteins and deposition of free fatty acids in adipose tissues. The adiposity in liver and skeletal muscles is also regulated by microorganisms through the changes of phosphorylated adenosine monophosphate-activated protein kinase (AMPK) levels. Abbreviations: LPL, lipoprotein lipase; VLDL, very low density lipoprotein. Reproduced with permission from Brown RK, Zehra-Esra I, Dae-Wook K, DiBaise JK. The Effects of gut microbes on nutrient absorption and energy regulation. Nutr Clin Pract. 2012;27:201-214.
Figure 5
Figure 5
Gut microbiota dysbiosis and the role of inflammation in the metabolic impairments of obesity. The origin of metabolic diseases is multifactorial but the impact of deleterious feeding habits is certainly the major factor responsible. This directly modifies intestinal ecology and we first showed that upon an increased intestinal permeability it led to an increased circulating concentration of LPS from Gram-negative bacteria of intestinal origin86,101 called metabolic endotoxemia. The inflammatory factors LPS and other bacterial fragments can translocate toward target tissues such as the blood, the liver, and the adipose depots or the arterial wall to interfere with cells from the immune system to generate the chronic low-grade inflammation required for the development of metabolic and cardiovascular diseases. Reproduced with permission from Burcelin R, Sermino M, Chabo C, et al. Acta Diabetol. 2011;48(4): 257-273.100
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