Obesity, Intestinal Inflammation and Probiotics

Obesity, Intestinal Inflammation and Probiotics

Dr Samantha Coulson and Professor Luis Vitetta
Medlab Clinical Ltd

The microbial communities that colonise the human gastrointestinal tract (GIT) have been collectively referred to as the gut microbiota. The resident commensal cohort adapts to the local environmental/milieu conditions of the human host and establishes a complex ecosystem in which host–microbe, milieu–microbe and microbe–microbe interactions oversee the composition and dynamics of the GIT microbial and host cell community.1

A recent analysis of gut microbial communities illustrates how the commensal community in the GIT, alter their make-up according to the milieu composition that is derived from different nutritional practices. The proposal has documented that there may be three predominant GIT microbial family types that predominate in the gut and have been designated as enterotypes. These include the Bacteroides, Prevotella, and Ruminococcus, families of bacteria.2 A subsequent study that also investigated the association of dietary and environmental variables with the gut microbiota reported that the GIT microbiome was an entity with functional plasticity. In effect this flexibility is subject to environmental/nutritional signal(s) adaptation as evidenced by changed patterns of enterotype governance.3

Furthermore, it is also becoming apparent that the GIT with its commensal cohort is a central regulator for the activities of end organs such as the kidneys, brain, adipose tissue, muscle and liver and as such may provide local prompts that are transmitted extra-intestinally to end organ sites. A scientific insight therefore has emerged that plausibly links the GIT with the physiology of end organ function that may influence health maintenance or trigger and support a disease state. Maintaining a healthy GIT milieu and intestinal epithelium with the administration of probiotics may constitute a novel therapeutic strategy for health.1

The Microbiome, Probiotics and Obesity

Several observational studies have reported differences at the phylum and genera levels of the GIT microbiota in children and adults, depending on weight status or energy intake. A recent meta-analysis of the obesity-associated GIT microbiota found a consistent difference in Bifidobacteria genera (Actinobacteria phyla) numbers between 159 obese and 189 control subjects (adults and children) from 6 published studies with low heterogeneity, showing obese subjects were significantly depleted in Bifidobacteria. For Lactobacillus (Firmicutes phyla), no consistent or significant summary effect could be found when comparing obese to control subjects.4 Research investigating microbial phyla associated with obese and lean individuals remains inconclusive.

Figure 1

Figure 1. The influence of GIT dysbiosis on obesity and insulin resistance.6

Recent findings suggest that a high-fat diet and the GIT bacterial cohort interact to promote early low-level inflammatory changes in the gut that contribute to the development of obesity and insulin resistance (see figure 1).5-6 The overall trend is that targeted probiotic preparations could positively influence weight reduction. Specifically, in a study with healthy infants7 it was demonstrated that probiotic administration significantly lowered levels of palmitoleic acid and significantly increased levels of putrescine. The data suggest that palmitoleic acid a major monounsaturated fatty acid (MUFA) that is strongly linked to visceral obesity was reduced with probiotic supplementation. While putrescine a polyamine with importance for gut integrity was beneficially increased. Probiotic supplementation in adulthood8 and during the childhood (from birth to 10 years)9 demonstrated that probiotics at least in part assisted with the control of abdominal visceral and subcutaneous fat. In an additional study, administration of a multi-species probiotic supplement provided a synergistic effect on overweight and obese individuals when provided with a weight loss diet.10 In a further study with overweight children a multi-strain probiotic formulation significantly demonstrated decreased blood lipid profiles.11 Tien et al.12 have reported that the anti-inflammatory effects of Lactobacillus casei are negatively associated with NF-ΚB activation. Therefore, is has been mechanistically hypothesised that the health properties of probiotics relevant to reducing caloric intake in the gut and in turn obesity could be related to peroxisome proliferator-activated receptor gamma (PPAR γ) activation, which then blocks the activity of NF-ΚB.13-14 Hence it is interesting to note that over-consumption of food triggers GIT pro-inflammatory bacterial activity; this then may induce GIT metabolic dysfunction increasing the risk of metabolic diseases. Whereas a healthy diet with an optimally balanced GIT microbiota that promotes regulated/controlled PPAR γ activation could alleviate or suppress the risk of developing metabolic diseases such as T2DM.

Picture: liver fatty hepatosis

Histology of the liver (Magnification by x100) demonstrating non alcoholic fatty liver disease.

Probiotics and NAFLD

Non-alcoholic fatty liver disease (NAFLD) is a significant health concern with a recently published meta-analysis concluding that up to 25% of the population, globally, represents NALFD at various disease stages including hepatic steatosis, to non-alcoholic steatosis, to cirrhosis, end-stage liver failure and hepatocellular carcinoma. NAFLD is considered the hepatic manifestation of the metabolic syndrome due to the close association between NAFLD and metabolic syndrome including abdominal obesity, hypertension, elevated fasting plasma glucose, raised serum triglyceride and low high-density lipoprotein cholesterol (HDL-C).15 A recent report has advanced the hypothesis that there exits a gut–liver axis that suggests the GIT microbiota may significantly affect liver physiology and act as a co–factor in the etiology of chronic liver disease.16 This hypothesis has stemmed largely from the longstanding practice of using lactulose in the treatment of hepatic encephalopathy.17 This then, suggesting gut microbiota involvement in the management of chronic liver disease. A GIT microbiota that sustains a persistent low level pro–inflammatory pathogenic profile could modulate liver damage caused by ethanol and other toxic compounds such as acetaldehyde, phenols and endotoxins.

Clinical studies that demonstrated efficacy were related to improving endotoxemia that in turn improved liver functionality.18-21 It would seem that the probiotic actions most relevant to chronic liver diseases are modification of intestinal barrier function and the prevention of bacterial/toxin translocations. Increased GIT overloads with Gram-negative bacteria, increased permeability and impaired immunity may all contribute to increased bacterial/toxin translocations. Furthermore, a strong correlation between the rate of bacterial/toxin overload and the severity of cirrhosis was demonstrated.22-26 Hence, multi-strain probiotics may alter gut flora and rescue the GIT microbiome towards a protective commensal bacteria profile with a concomitant increase in GIT epithelial barrier function.


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