Is there a “brain microbiome”? No

17th January 2025

Our experts Prof Mark Pallen, Dr Falk Hildebrand and Dr Aimee Parker explain that there is no evidence for a brain microbiome

In recent months, sensational headlines have appeared in respected outlets such as New Scientist and The Guardian, suggesting the presence of a so-called “brain microbiome”—that is, a community of microbes living in the human brain.

We and other experts in medical microbiology and microbial genomics have expressed strong reservations about these claims in letters to the editors (Letter to New Scientist, Letter to Guardian). These concerns revolve around a key point: there is no evidence of a resident microbial community in the healthy human brain. Sequence datasets derived from human brains might indeed contain traces of bacterial DNA, but this can be readily explained by contamination rather than the existence of a resident microbial community.

Here, we explore the background to this issue, while also stressing the importance of peer-review and why caution is essential when dealing with such extraordinary claims.

What is a microbiome?

The term “microbiome” is used to refer to the collection of microorganisms—bacteria, fungi, viruses, and parasites—that reside in a particular environment. Popular examples include the gut microbiome (microbes living in our intestines) and the skin microbiome. These microbial communities can have profound effects on health and disease.

Research on microbiomes is complex and relies on advanced DNA sequencing technologies, sophisticated computational analyses, culture-based methods and careful contamination controls.

The suggestion of a “brain microbiome” implies that there is a stable, living community of microbes in the human brain, just as there is in the gut or on the skin. But this challenges the expert view of medical microbiologists that there are no microbes living in healthy human brains.  For over a century and a half, routine practice within the discipline of medical microbiology has show that the healthy human brain is a sterile environment without any resident microbes.

More generally, there is no scientific evidence of a brain microbiome, including no imaging, DNA-sequence-based or culture-based or immunological evidence.

Microbes found in the brain represent infection rather than a microbiome

This is not to say that microbes are never found in the brain. Microbes that cause disease—such as Borrelia burgdorferi, which causes Lyme disease, or fungal pathogens like Cryptococcus neoformans—can invade the brain and cause neurological symptoms.

However, these microbes in the brain represent examples of “infections”, not evidence of a native microbial community. Similarly, vaccines may bring cognitive benefits, but these can be explained by their role in preventing infections or modulating immune responses and inflammation, rather than any direct impact on a “brain microbiome”.

Unscrutinised claims

The most prominent claims of a brain microbiome featured in New Scientist and the Guardian come from a preprint by Hu Xinyue and colleagues.

A preprint is a piece of scientific work published online without undergoing scholarly peer review by independent experts. Peer review is the cornerstone of modern science. It involves independent experts carefully evaluating a paper’s methods, results, and interpretation before publication in a scientific journal. While the preprint model allows rapid sharing of findings, it also means the research has not been subjected to this critical scrutiny and so should be treated with caution, particularly by non-experts.

The study reported by Hu and colleagues analysed DNA sequences from other researchers’ experiments. These original researchers had collected RNA from human brain tissue (for unrelated purposes) and then performed high-throughput sequencing of DNA generated from this RNA.

The authors of the preprint claim to have found bacterial DNA sequences in these datasets and they interpret this as evidence for a functioning microbial community in the brain. While there may well be bacterial DNA sequences in these datasets, there are many reasons to doubt whether this preprint does actually provide evidence of a brain microbiome.

The “contaminome”

The pervasive problem of the human “contaminome”— spurious bacterial, viral, and computational contamination in human genome sequences— has been highlighted in a recent publication by Brianna Chrisman and colleagues. Contamination remains one of the biggest hurdles in studies of usually sterile samples including those from the brain or placenta.

Bacterial cells or DNA sequences or signals can sneak into samples at many stages:

Since the human brain is normally sterile, even tiny amounts of contamination can appear significant when you sequence deeply. It takes meticulous controls and repeated validations to confirm whether any detected bacterial DNA truly comes from the brain itself.

In largely re-using existing sequence data, Hu and colleagues have not been able to control for such contamination, so contamination remains overwhelmingly the most plausible explanation for their reported findings. The paper includes a far-fetched claim that the human brain is home not just to bacteria but also to plants and algae, which supports the conclusion that the any non-human DNA detected is likely due to contamination.

The need for consistency and consilience

The preprint by Hu et al sits alongside several other papers reporting bacterial signatures from the human brain. However, these fail to give any consistent or precise picture. The English philosopher William Whewell (1794 –1866) coined the term “consilience” to explain how we should expect multiple lines of independent evidence to converge on the same conclusion, before a claim can be accepted as true.

For a claim as extraordinary as a bacterial population living in the brain, we would look for:

  1. Culture-based evidence. If living bacteria are truly abundant in the brain, we might expect them to have been cultured in medical microbiology labs, particularly as most of the bacteria reported in the Hu et al preprint can be grown easily in the lab. Yet, routine analyses over more than a century of medical microbiology have consistently revealed no bacterial growth from healthy brain tissue.
  2. Imaging evidence. We now have an electron microscopy reconstruction of the human cerebral cortex at nanoscale resolution, but neither advanced imaging or even Gram-staining of the human brain has never shown a thriving community of bacteria
  3. Immune responses. The human immune system is exquisitely sensitive to the presence of bacteria in human tissues. If the brain were home to bacteria, why would we not routinely see inflammation or immune responses? If bacteria were there, what’s to stop them dining on brain cells?
  4. Consistent findings. There is no agreement between the reported studies on precisely which microbes are present or most abundant in brain tissues. Instead, findings typically mirror the “rogues’ gallery” of common contaminants reported by Salter and colleagues.
  5. Methodological rigour. Appropriate controls for every step of such complex protocols, proving that methods used correctly report positive and negative findings, together with healthy scepticism in data interpretation.

Put simply, if bacteria were really living in the brain, we would expect to see them by more than just inconsistent and questionable DNA sequencing signals. This mirrors controversies around other supposed microbiomes associated with the placenta or cancers, which have failed to withstand independent scrutiny and even led to high-profile retraction of a paper.

As science communicator Carl Sagan made clear, extraordinary claims require extraordinary evidence. True breakthroughs in science emerge from carefully designed, reproducible studies that stand up to scrutiny from expert peers.

The claim that healthy human brains contain their own microbiome remains unsubstantiated. Sequence datasets derived from human brains might indeed contain traces of bacterial DNA, but this can be readily explained by contamination rather than the existence of a resident microbial community.

Future directions

Efforts to explore the role of microbes in neurological conditions are welcome, but they must be grounded in robust and reproducible science, drawing on well-established approaches for avoiding contamination of datasets and over-interpretation of results.

Though there is no “brain microbiome”, there is plenty of exciting and promising work underway on the gut-brain axis—the links between the gut microbiome and the brain—including here at the Quadram Institute.

Related Targets

Targeting the understanding of the microbiome

Understanding the Microbiome

Related Research Groups

Pallen group

Mark Pallen

Falk Hildebrand

Related Research Areas

A green background with an illustration of a gut full of microbes.

Food, Microbiome and Health