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Digestive System of the Obese vs. Non-Obese

Digestive System Of The Obese Vs. Non-Obese

Authors: Marcus Free MD, Rouzbeh Motiei-Langroudi MD, Waqar Ahmad PhD, Kelly Daly RDN, and Don Juravin (Don Karl Juravin).

Abstract (Research Summary)

  1. Obese individuals have a higher fasting gastric volume (by 6%) and accelerated gastric emptying (by 17% for solids and 30% for liquids) (Acosta 2015).
  2. Obese individuals have a blunted response of the afferent vagus nerve (which signals stomach volume to the brain) (Acosta 2014).
  3. Obese individuals have a less diverse gut bacterial community (Karlsson 2015, Villanueva-Millán 2015, Al-Ghalith 2015).
  4. In obese individuals, the gut flora ratio changes to a less overall phylum diversity and a greater proportion of Firmicutes than Bacteroidetes (Bell 2015, Al-Ghalith 2015, Moran 2014, Ley 2006).
  5. Obese individuals have a higher concentration of Enterobacteriaceae and a lower concentration of Desulfovibrio and Akkermansia muciniphila-like bacteria (Karlsson 2015, Bradlow 2014).
  6. The gut flora in obese individuals harvests energy more effectively and increases adiposity (Graham 2015).
  7. In obese individuals, altered levels of ghrelin, obestatin, glucagon-like peptide 1, and gastric inhibitory peptide change the eating behavior, amount of food eaten, feelings of hunger and satiety, and energy expenditure (Field 2010).
  8. Obese individuals have reduced secretion of GLP-1 after glucose administration (by 37%), resulting in higher insulin resistance (Hussein 2014).
  9. Obese individuals have lower levels of satiety inducing gut hormones, including cholecystokinin, GLP-1, enteroglucagon, oxyntomodulin, peptide YY, and fibroblast growth factor-19 (Acosta 2015, Ranganath 1996).
  10. In obese individuals, plasma ghrelin levels do not decline after a meal (English 2002).

Overview

Obesity results from increased energy intake and decreased energy expenditure. The digestive (aka gastrointestinal or GI) system has a key role in the pathogenesis of obesity. Changes in digestive system hormones, digestive tract structure and motility, and the inhibition of mechanisms that restrict calorie intake result in weight gain. However, It is not clear if the digestive system changes cause or are affected by obesity (Acosta 2014).

Structural Changes in Obese Digestive System

The volume of the stomach is increased in obese people (by 6%), causing them to eat more to induce satiety.

  • Obese individuals have a higher gastric volume at fasting and satiation. A 50ml increase in the fasting gastric volume is associated with ~115 kcal more ingested at maximum satiation (Acosta 2014).
  • Obese individuals have a higher fasting gastric volume (by 6%) (Acosta 2015), contributing to decreased and later satiation.

Functional Changes in Obese Digestive System

Obese individuals have a faster gastric emptying and also blunted vagus nerve activity signaling satiety.

  1. Obese individuals have an accelerated gastric emptying (by 17% for solids and 30% for liquids) (Acosta 2015), contributing to later satiation.
  2. Obese individuals have a blunted response of the afferent vagus nerve (which signals stomach volume to the brain) to ingestion of a meal (Acosta 2014).
  3. Vagal nerve responses to both mechanical and chemical stimuli are modified in obesity to a state of blunted anorexigenic (i.e. satiety) and potentiated orexigenic (i.e. eating) capacity (Kentish 2015).

Gut Flora Changes in Obese Digestive System

Obese individuals have a different gut flora composition and number compared to non-obese. Changes in gut flora composition can induce weight gain due to changes in energy extraction from the diet and the modulation of lipid metabolism, carbohydrate digestion and absorption, endocrine functions, and the immune system.

Gut Flora Changes in Obesity

  • The gut flora in a healthy human is comprised of 1013 to 1014 microorganisms from 500-1000 different species (Moran 2014, Escobedo 2014).
  • Obese individuals have a different composition of gut microbiota (Cardinelli 2015).
  • Obese individuals have a less diverse bacterial community in the gut compared to normal weight (Karlsson 2015, Villanueva-Millán 2015, Al-Ghalith 2015).
  • In healthy individuals, the most common species are the phylum Firmicutes (including Clostridium, EnterococcusLactobacillus, and Ruminococcus) and Bacteroidetes (including Prevotella and Bacteroides genera). In obese individuals, the ratio changes to a less overall phylum diversity and a greater proportion of Firmicutes than Bacteroidetes (Moran 2014).
  • Obese individuals have a higher concentration of Enterobacteriaceae and a lower concentration of Desulfovibrio and Akkermansia muciniphila-like bacteria compared to non-obese (Karlsson 2015, Bradlow 2014).
  • Obese individuals have an increased ratio of the gram-positive Firmicutes to the gram-negative Bacteroidetes (the obesity pattern) (Bell 2015, Al-Ghalith 2015, Ley 2006).

Effects of Gut Flora Changes on Weight

  • The gut flora in obese individuals harvests energy more effectively, increases adiposity, and aggravates inflammatory mechanisms and metabolic dysfunction (Graham 2015).
  • 20% increase in the proportional representations of Firmicutes and Bacteroidetes increases and decreases nutrient absorption by 150 kcal, respectively (Moran 2014).
  • Transplant of the healthy gut flora from normal-weight mice into either germ-free or obese mice results in weight loss (Graham 2015, Bradlow 2014).
  • Transplant of the unhealthy gut flora from obese mice into either germ-free or normal weight mice results in weight gain (Bradlow 2014).

Mechanism of Gut Flora Changes Effects on Weight

  • Change of gut flora in obesity results in increased gut permeability, increased endocannabinoid tone,  excessive fat accumulation, low-grade inflammation, and altered metabolism. This sequence of events increases energy intake and decreases energy expenditure, resulting in obesity (Blaut 2015, Tai 2015, Moran 2014, Bradlow 2014).
  • Increased Firmicutes to Bacteroidetes ratio in obese gut results in the formation of increased amounts of metabolic endotoxins (Bradlow 2014).
  • Decreased concentration of Akkermansia in the obese gut results in thinning of mucus and weakening of intestinal lining. This permits metabolic endotoxins formed by other gut flora microbes (like Firmicutes) to enter the blood and cause chronic inflammation (Bradlow 2014).
  • In obese individuals, the change in the gut flora profile results in increases in species with more efficient energy generating, leading to obesity (Bradlow 2014).
  • Change in gut flora in obese individuals activates macrophages and enables macrophages to infiltrate and enter the adipose tissue, finally inducing insulin resistance (Escobedo 2014).

Gut Hormonal Changes in Obese Digestive System

Different gut hormones act in an integrated fashion to modulate appetite and energy expenditure. Obese individuals have altered the levels and function of some digestive hormones.

Functions of Gut Hormones

  • Various gut hormones such as ghrelin, cholecystokinin, peptide YY, pancreatic polypeptide, glucagon‑like peptide 1 (GLP-1), glucagon, oxyntomodulin, and islet amyloid polypeptide modulate appetite and energy expenditure (Field 2010).
  • Gut-derived hormones alter feeding behavior (Melvin 2016).
  • Ghrelin is a hunger hormone and is elevated during periods of fasting, resulting in eating (Melvin 2016).
  • Ghrelin induces a positive energy balance, increases adiposity gain, and increases caloric storage (Mihalache 2016).
  • In normal-weight individuals, ghrelin levels fall by the presence of food in the stomach irrespective of the caloric value of a meal. Consuming small amounts of guar gum or psyllium fiber between meals helps to keep ghrelin down (Nedvídková 2003).

Changes in Gut Hormones in the Obese

  1. Obese individuals have reduced secretion of GLP-1 after glucose administration (by 37%), resulting in higher insulin resistance (Hussein 2014).
  2. Obese individuals have lower levels of satiety inducing gut hormones, including cholecystokinin, GLP-1, enteroglucagon, oxyntomodulin, peptide YY, and fibroblast growth factor-19 (Acosta 2015, Ranganath 1996).
  3. Obese individuals have increased dipeptidyl peptidase-4 (DPP-4) activity, resulting in decreases in GLP-1 and GIP, finally contributing to Inflammatory state in the gut and insulin resistance (Zietek 2016).
  4. Obese individuals have lower levels of obestatin, a gut hormone that decreases appetite and delays stomach emptying (Wang 2014).
  5. In obese individuals plasma ghrelin levels do not decline after a meal, leading to increased food consumption (English 2002).
  6. Obese individuals feel hedonic hunger (i.e. eat for pleasure), mediated partly through the effects of ghrelin on dopaminergic neurons (Dickson 2011).
  7. Obese individuals develop food addictions as ghrelin increases the incentive value of food (Dickson 2011).

References

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Footnote

This research was sponsored by GLOBESITY FOUNDATION (nonprofit organization) and managed by Don Juravin. GLOBESITY Bootcamp for the obese is part of GLOBESITY FOUNDATION which helps obese with 70 to 400 lbs excess fat to adopt a healthy lifestyle and thereby achieve a healthy weight.

Tags: obese, gut flora, GLOBESITY FOUNDATION, weight-loss, metabolism

Points For The Public:

  1. Obese individuals have a higher stomach volume (by 6%)
  2. Obese individuals have blunted response of the afferent vagus nerve (which signals stomach volume to the brain)
  3. Obese individuals have a less diverse gut bacterial community
  4. The gut flora in obese individuals harvests energy more effectively and increases adiposity
  5. In obese individuals, altered levels of ghrelin, obestatin, glucagon-like peptide 1, and gastric inhibitory peptide change the eating behavior, amount of food eaten, feelings of hunger and satiety, and energy expenditure