Science and Technology
12.12.2011

Research linking obesity and diabetes to bacteria in the gut

A study of Unicamp published in Nature showed that lean and obese had a different type of intestinal flora

Foto: Antoninho Perri/Ascom/Unicamp
The pesquisdsores Gabarra Alexandre Oliveira, Bruno Carvalho de Melo and Andrea M. Caricilli (left to right. To right.)
The pesquisdsores Gabarra Alexandre Oliveira, Bruno Carvalho de Melo and Andrea M. Caricilli (left to right. To right.)

Research conducted by the College of Medical Sciences (FCM) at Unicamp show bacteria in the gut as a new line of research on obesity and diabetes. In 2006, a study published in Nature showed that lean and obese had a different type of intestinal flora. That caught the attention of researchers from the Laboratory for Clinical Research on Insulin Resistance (Lycra) FCM.

Two of the candidates to mediate the effects of intestinal flora metabolism are TLR2 and TLR4 receptors, proteins encoded by a gene family of Toll-like (Toll-like receptors). The TLR2 is a receptor protein present in the membrane of certain cells. He recognizes antigens and transmits signals to cells of the immune system. The TLR4 is also a recipient of the immune system. It detects mainly lipopolysaccharide (LPS) component present in the cell wall of gram-negative bacteria existing in the intestine.

The animal fat is activated receptor TLR4. The first thing we found this animal was a high LPS. LPS increases the absorption of high energy that accumulates as fat. We then looked down the high LPS and direct candidates were bacteria of the gastrointestinal tract, said Saad.

But to arrive at this discovery, it was necessary to assemble the puzzle from three studies conducted by researchers at the Lycra. The work resulted in papers published in international journals.

The physical educator Alexandre Oliveira Gabarra researched the effects of exercise on reducing the circulation of lipopolysaccharide, the TLR4 receptor activation and improves insulin signaling in tissues of rats with fat diet-induced obesity. The biomedical Bruno Carvalho de Melo studied the modulation of intestinal microbiota in the improvement of insulin signaling in mice fed high fat content.

Already biologist Andrea Moro Caricilli studied the intestinal microbiota as a key modulator of insulin resistance in knockout mice. From the study, Andrea noted that mice that had no TLR2 protein had a phenotype similar to that observed in metabolic syndrome and with a bacterial composition similar to that found in obese individuals, and increased the proportion of bacteria of the phylum Firmicutes.

Inflammation <b> </ b>

It became increasingly evident that insulin resistance induced by obesity, is associated with a chronic inflammation of adipose tissue, skeletal muscles and internal organs like the liver. Recent studies by the research group of Lycra show that a mutation in the TLR4 receptor plays a central role in linking insulin resistance, inflammation and obesity.

The TLR4 is a receptor essential for the recognition of lipopolysaccharide (LPS). The concentrations of LPS significantly increased after ingestion of meals high in fat and carbohydrates. The fat intake leads to increased intestinal permeability, because LPS is soluble in fat.

<b> Insulin Resistance </ b>

There are approximately 100 trillion bacteria in the gut, representing 400 to 1,000 species. From the hypothesis that the gut flora of obese and lean is different, both in humans and rodents, the biomedical Bruno Carvalho de Melo sought a way to modulate the intestinal flora and demonstrate its relationship with insulin resistance and the obesity.

The strategy was to use antibiotics. Strain of Swiss mice were subjected to high-fat diet for eight weeks. The researcher used a cocktail of broad spectrum antibiotics and treated animals during the induction of obesity. The animal was treated with antibiotics all physiological components improved in relation to the animal that received only high-fat diet. Both the liver, muscle and adipose tissue, activation of all proteins of the signaling pathways of insulin was improved compared to animals not treated, said Bruno.

Microbial <b> </ b>

The research biologist Andrea Mora Caricilli was the missing piece to understand the relationship between gut flora and obesity. She used a group of mice genetically modified to not TLR2 receptor expression, called knockout. We see that the knockout mice had an increased concentration of lipopolysaccharide compared to control animals. This increase led us to investigate what was the composition of intestinal flora. We found that the intestinal flora of these animals had a higher proportion of Firmicutes, as seen in the obese, said Andrea.

According to research, changes in intestinal microbiota have been accompanied by an increased absorption of LPS, subclinical inflammation, insulin resistance, glucose intolerance and later obesity.

Any regulation of the immune system in the gut, the growth and predominance of one type of bacteria depend on the food you consume and the environment in which you are entered. Depending on the intestinal flora established in your body, there will be a greater or lesser absorption of fat and a more or less likely to develop low-grade inflammation and insulin resistance. It is not clear how the selection occurs in the gut bacteria, the researcher concluded.

Source: UNICAMP