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Using metagenomics to analyse bacteria in the human gut microbiome

Researchers have recently used metagenomics to investigate the evolution and persistence of bacteria in the human gut microbiome.

The human gut microbiome

A microbiome is the genetic material of all the microbes that live inside the human body, including bacteria, fungi, protozoa and viruses. One person’s microbiome consists of 200 times more genes than a human genome and is thought to weight over 2 kilograms.

The gut microbiome is a complex community of microbes that help to digest food, regulate the immune system, protect against pathogens and produce vitamins. It is possible for human gut bacterial strains to co-exist with their hosts for years. Therefore, maintaining a stable and healthy gut microbial population is mutually beneficial – for people and for bacteria.

Bacterial persistence is the continued occurrence of a bacterial strain. The mechanisms behind bacterial persistence remain largely unexplored. Nevertheless, unravelling this complex process will provide education about which bacteria may need protection, or restoration, in the human gut.

Metagenomics and gut bacteria persistence

Do strains of bacteria in the gut persist due to their own traits, or is gut bacteria persistence enabled by the host?

A group of scientists recently used metagenomics to answer these questions. Researchers from the Earlham Institute, the Quadram Institute and the European Molecular Biology Laboratory worked together on a project that investigated the evolution and persistence of bacteria in the human gut microbiome. They explored how gut bacterial persistence was influenced by common factors such as age, family members, geographical region and antibiotic usage. The team examined 5,278 human faecal metagenomes sampled from a variety of ages and nationalities.

The key findings were as follows:

  • Gut bacterial persistence was widespread but heterogenous between taxa.
  • Bacterial persistence differed with host age, delivery mode and antibiotic usage.
  • There was a link between persistence and family transmission of gut bacteria.
  • Persistent bacteria were dispersed at a local scale by blooming strains.
  • Bacterial dispersal strategies were revealed when persistence, family association and phylogeography were compared.
  • Dispersal strategies related to bacterial evolution.

Overall, the analysis showed that bacteria present in the human microbiome were very persistent, with 90% of strains persisting for over a year. It was also discovered that the persistence dropped slightly to 80% in new-born babies. This confirmed that there is a continuous exchange of gut microbes at very early ages. The team found that the microbiome reached a stable state by about 10 years old.

The researchers also categorised the gut bacteria into three main groups:

Tenacious bacteria – These were the most persistent and well-adapted for the human gut. These strains were highly likely to be lost from the microbiome following the use of antibiotics. This loss may be permanent, raising a particular concern regarding the misuse of antibiotics.

Heredipersistent bacteria – These strains were inherited and typically transmitted within families. Cycles of reinfection from external sources were key to their persistence. This suggests that their replacement through singular medical interventions, such as faecal transplants, may be ineffective.

Spatiopersistent bacteria – These strains were clustered within geographic areas. They were also less persistent in infants.

Manipulating the microbiome for health

This research successfully described how different bacterial dispersal strategies can shape long-term persistence of the human gut microbe. Future exploration in this area could lead to rapid advances in manipulating the microbiome for health and, ultimately, generate more well-informed clinical decisions. The data that was collected could be used to inform tailored probiotics, found in both food and supplements. Plus, the new insight gained has the potential to drive the production of medical interventions designed to treat various gut diseases. Furthermore, novel mitigation strategies against the misuse of antibiotics could be created.

Dr Falk Hildebrand, the group’s leader, said: “Our study gave us a much better idea of which gut bacteria are closely associated with their host, and which are more prone to switch between hosts. This is important information to inform pro-prebiotics and most medical applications targeting the human gut microbiome.”

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