Lead (Pb) is a persistent environmental contaminant that is toxic to humans, primarily in the developmental stages of life. It is believed that environment and nutrition play a role in determining health. Most recently, it has been recognized by the National Institute of Environmental Health Sciences that the interaction between pathogens and toxic agents may contribute to disease development in humans. In fact, epidemiological studies suggest that there may be a correlation between lead exposure and obesity in children and that this effect may be long-lasting, resulting in adulthood obesity.

Perinatal lead exposure in mice

The microbiome has recently been recognized as contributing to health and disruptions in gut microbiota constitution as been associated with chronic illnesses. To investigate the phenomena of Pb-induced obesity, mice were exposed to lead during the perinatal period.  Researchers studied how lead exposure around the time of birth impacted gut microbiota, and then watched to observe whether changes to the microbiome influenced bodyweight.

Microbiome Imbalance

They found that exposure to lead early in development did alter the bacterial composition of the digestive tract.  Pb affected the resilience and diversity of bacteria normally present in the gut; disrupting the balance between aerobic and anaerobic bacterium. Bacteroidetes (gram-negative) were severely reduced in Pb-exposed mice, while firmicutes (gram-positive). were significantly increased. This is important because the ratio of bacteroidetes to firmicutes has been shown to be involved with maintaining health in humans. People with obesity are more likely to have less bacteroidetes in proportion to firmicutes.  This suggests that lead imparts positive selection for certain bacterium. Indeed, there were greater amounts of Desulfovibrionales, Barnesiella, and Clostridium XIVb in Pb exposed mice, while Lactococcus, Enterorhabdus, and Caulobacterales  were more abundant in mice who were not exposed to Pb.

› Anaerobic Gram-negative sulfate reducing bacteria

› Found in gastrointestinal tract of animals and humans

› Found in the in the environment (soil and water).

› Implicated in IBD (inflammatory bowel disease).

 

Gut Microbiota Imbalance  Increased Bodyweight

Most importantly, researchers found that male mice with perinatal lead exposure weighed more than male mice who were not exposed to lead, and that this affect persisted into adulthood—even after cessation of Pb exposure. Pb-exposed male mice had altered and imbalanced gut microbiomes that were consistent with the presence of “obese microbiota” and the lack of protective bacterium in the digestive system. Pb enhanced growth of Desulfovibrio, a bacteria that produces the precursor to potentially toxic trimethylamine N-oxide, which is associated with cardiovascular disease and cancer. Pb completely destroyed the presence of the bacterium Akkermansia, which was recently shown to improve metabolic obesity in humans. The presence of Akkermansia is partially protective against inflammation and the formation of fat tissue.

Sex-relevant Factors

Interestingly, female lead-exposed mice—although having altered gut microbiota—did not go on to  have increased body-weight in comparison to non-exposed females. It is suggested that Pb-induced alteration of the gut microbiota, coupled with other sex-relevant factors, such as hormones, is the underlining reason for increased body-weight.  Indeed, sex plays a significant part in the development of obesity.  Figuring out what factors in females confer protection might allow researchers to develop preventative measures and treatments for obesity in humans.

Akkermansia muciniphila

• Mucin-degrading bacterium
• Involved in maintenance of gut barrier and glucose homeostasis
• Loss of abundance in people with obesity and diabetes

Summary

Early exposure to the toxic metal lead during development, before or after birth, has been shown to dramatically alter the composition of the microbiome and results in increased body-weight in males.  Imbalances to the normal proportions of Bacteriodete/firmicute bacteria in the gut are linked to obesity, irritable bowel syndrome, diabetes, and cancer. Perinatal lead exposure has long-lasting effects on the gut microbiota even after exposure has stopped, and can influence body-weight into adulthood.

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