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Archive Highlight: New evidence on the virome in gut-brain communication and stress, with Nathaniel Ritz and Thomaz Bastiaanssen

Continuing our series on the microbiota-gut-brain axis, we are highlighting Episode 34 from our archives. In this episode, the ISAPP hosts discuss a new study on how the gut virome affects the host during stress, with Nathaniel (Nate) Ritz from the Institute for Systems Biology in Seattle, USA and Thomaz Bastiaanssen from APC Microbiome Ireland. The guests give an overview of the microbiota-gut-brain axis, then delve into a new study they led on the virome and its effects on stress responses in mice.

Key topics from this episode:

  • The gut and the brain communicate in various ways, and the microbiota play a role in some of these modes of communication. Various studies use animal models to look at mechanisms that might be applicable to humans.
  • Why would the microbiota affect the human brain? Because we evolved with a ‘background’ of microbes and have relied on them as we evolved. For example, gut microbes produce metabolites the human body is unable to produce by itself.
  • The newly published paper is titled “The gut virome is associated with stress-induced changes in behaviour and immune responses in mice”.
  • Most microbiota-gut-brain axis research to date has looked at the bacterial component of the microbiome, but this misses the bigger context. The virome is the collection of viruses in the gut, mostly consisting of bacteriophages (which infect bacteria in the gut). This study focused on the virome and how it influenced the gut bacteriome as well as host behavior.
  • Bioinformatics challenges exist when working with the virome for several reasons. For one, distinguishing the biology of a bacteriophage from its host can be challenging.
  • The study used a fecal virome transplant: taking a fecal sample, removing the cellular organisms and small particulates so that the bacteriophages were left over, and then concentrating them and administering them. The researchers took this entire virome from a mouse, then transferred it back to the same individual mouse while it was undergoing stress.
  • After stress, differences were seen in the mouse gut bacteriome and virome. The mice had higher anxiety- and depression-like behaviour, plus changes in their immune systems. But after the fecal virome transplant, some of their behaviours were improved.
  • Do the viruses impact the host nervous system directly, or do they only affect the host by way of the bacteriome? This is not fully known, but there appears to be very little interaction of the bacteriophages with the host. 
  • Analysis of the gut bacteriome or virome must respect the compositional nature of the data. The types of measurements used to analyze the microbiome and virome are confounded by compositional effects, and in the field this is not respected as much as it should be.
  • The next step after this study is to explore the changes in microbiome function in the mice, perhaps pinpointing which bacterial groups need to be changed to normalize the mouse behaviours.

Episode links:

About Nathaniel Ritz:

Dr. Nathaniel Ritz completed his PhD in Prof. John Cryan’s lab at APC Microbiome Ireland where he studied the role of the bacteriome and the virome in social and stress-related disorders. His interests lie in elucidating microbiota-host interactions and establishing microbiota causality within the microbiota-gut-brain axis. Nathaniel has recently moved to Seattle, Washington, USA, to join the lab of Dr. Sid Venkatesh as a postdoctoral fellow at the Institute for Systems Biology to further unravel the mechanisms underpinning microbe-host interaction. Outside of the lab, Nathaniel is an avid rock climber, dog walker, and partner to fellow scientist Dr. Minke Nota. More details and current position can be found at https://venkatesh.isbscience.org/

About Thomaz Bastiaanssen:

Dr. Thomaz Bastiaanssen is the lead bioinformatician in Prof. John F. Cryan’s microbiota-gut-brain axis group in Cork, Ireland. He is interested in the ecological dynamics governing host-microbe communication and how this complex interplay can impact human well-being. He will soon transition to a new role at Amsterdam UMC, the Netherlands, where he will continue to study the microbiome gut-brain axis. Besides working on multi-omics analyses, he enjoys horror stories, tabletop games and spending time with his wife, son, and corgi. His website can be found at: https://thomazbastiaanssen.github.io/
pigs in mud

The gut-brain axis in livestock animals: Is there a place for biotics in changing pig behavior?

By Prof. Seppo Salminen PhD, University of Turku, Finland

When pigs are kept as livestock, ‘manipulative behaviour’ is relatively common and it most often consists of biting, touching, or close contact with ears or tails of pen mates, without always resulting in visible wounds. Such pig behavior can cause stress and sometimes results in physical injuries. Chronic stress, nutritional deprivation, diet formulation, health problems, environmental discomfort, high stocking density and competition over resources are among the reported risk factors for tail biting in pigs. However, the precise factors behind behavioral problems in domesticated pigs remain poorly understood. It has been suggested that manipulative behavior may be associated with gut microbiota composition and activity via the gut-brain axis, with potential influence from the metabolites produced by gut microbes.

A multidisciplinary team of researchers recently assessed manipulative pig behaviour and gut microbiota interrelations (König et al. 2024). The aim was to identify pigs performing tail and/or ear manipulation (manipulator pigs) and to compare their fecal microbiota with that of control pigs not manifesting such behaviour. The study was conducted by analyzing video recordings of 45-day-old pigs. Altogether 15 manipulator-control pairs were identified (n = 30). Controls did not receive nor perform manipulative behaviour.

Rectal fecal samples of manipulators and controls were compared on two parameters: (1) culturable lactobacilli, and (2) microbiota composition. 16S PCR was used to identify Lactobacillaceae species after culture isolation, and 16S amplicon sequencing was used to determine fecal microbiota composition. The researchers found fewer culturable Lactobacillaceae species in fecal samples of pigs performing manipulative behaviour, with seven culturable Lactobacillaceae species identified in control pigs and four in manipulator pigs. Manipulators (p = 0.02) and female pigs (p = 0.005), however, expressed higher overall counts of Lactobacillus amylovorus, and the researchers found a significant interaction (sex * status: p = 0.005) with this sex difference being more marked in controls. Manipulator pigs tended to express higher total abundance of Lactobacillaceae but lower alpha diversity. A tendency for an interaction was seen in Limosilactobacillus reuteri (sex * status: p = 0.09). The results add to the findings of an earlier study reporting that intestinal microbiota was changed and lactobacilli were more abundant in a negative control group compared with biting pigs (Rabhi et al. 2020). Taken together, these studies suggest that specific lactobacilli  as well as low diversity of Lactobacillaceae may be factors impacting manipulative behavior.

Manipulative behavior is an important challenge in swine production as it impacts animal welfare and health and the economics and safety of the pork meat supply chain. With emerging information on the gut-brain axis in various animals, scientists are exploring the potential contributions of intestinal microbiota to such behaviors. With recent studies suggesting that there may be a link between observed low diversity in species of Lactobacillaceae and the development of manipulative behaviour, perhaps specific biotics could be used to increase and modulate lactobacilli (selected species and diversity) to control tail and ear biting in pigs. Studies in the future may investigate this possibility.

References

König E, Heponiemi P, Kivinen S et al. Fewer culturable Lactobacillaceae species identified in faecal samples of pigs performing manipulative behaviour. Sci Rep. 2024;14:132. doi: 10.1038/s41598-023-50791-0.

Rabhi N, Thibodeau A, Côté JC, Devillers N, Laplante B, Fravalo P, Larivière-Gauthier G, Thériault WP, Faucitano L, Beauchamp G, Quessy S. Association Between Tail-Biting and Intestinal Microbiota Composition in Pigs. Front Vet Sci. 2020 Dec 9;7:563762. doi: 10.3389/fvets.2020.563762.

Episode 34: New evidence on the virome in gut-brain communication and stress, with Nathaniel Ritz and Thomaz Bastiaanssen

In this episode, the ISAPP hosts discuss a new study on how the gut virome affects the host during stress, with Nathaniel (Nate) Ritz from the Institute for Systems Biology in Seattle, USA and Thomaz Bastiaanssen from APC Microbiome Ireland. The guests give an overview of the microbiota-gut-brain axis, then delve into a new study they led on the virome and its effects on stress responses in mice.

Key topics from this episode:

  • The gut and the brain communicate in various ways, and the microbiota play a role in some of these modes of communication. Various studies use animal models to look at mechanisms that might be applicable to humans.
  • Why would the microbiota affect the human brain? Because we evolved with a ‘background’ of microbes and have relied on them as we evolved. For example, gut microbes produce metabolites the human body is unable to produce by itself.
  • The newly published paper is titled “The gut virome is associated with stress-induced changes in behaviour and immune responses in mice”.
  • Most microbiota-gut-brain axis research to date has looked at the bacterial component of the microbiome, but this misses the bigger context. The virome is the collection of viruses in the gut, mostly consisting of bacteriophages (which infect bacteria in the gut). This study focused on the virome and how it influenced the gut bacteriome as well as host behavior.
  • Bioinformatics challenges exist when working with the virome for several reasons. For one, distinguishing the biology of a bacteriophage from its host can be challenging.
  • The study used a fecal virome transplant: taking a fecal sample, removing the cellular organisms and small particulates so that the bacteriophages were left over, and then concentrating them and administering them. The researchers took this entire virome from a mouse, then transferred it back to the same individual mouse while it was undergoing stress.
  • After stress, differences were seen in the mouse gut bacteriome and virome. The mice had higher anxiety- and depression-like behaviour, plus changes in their immune systems. But after the fecal virome transplant, some of their behaviours were improved.
  • Do the viruses impact the host nervous system directly, or do they only affect the host by way of the bacteriome? This is not fully known, but there appears to be very little interaction of the bacteriophages with the host. 
  • Analysis of the gut bacteriome or virome must respect the compositional nature of the data. The types of measurements used to analyze the microbiome and virome are confounded by compositional effects, and in the field this is not respected as much as it should be.
  • The next step after this study is to explore the changes in microbiome function in the mice, perhaps pinpointing which bacterial groups need to be changed to normalize the mouse behaviours.

Episode links:

About Nathaniel Ritz:

Dr. Nathaniel Ritz completed his PhD in Prof. John Cryan’s lab at APC Microbiome Ireland where he studied the role of the bacteriome and the virome in social and stress-related disorders. His interests lie in elucidating microbiota-host interactions and establishing microbiota causality within the microbiota-gut-brain axis. Nathaniel has recently moved to Seattle, Washington, USA, to join the lab of Dr. Sid Venkatesh as a postdoctoral fellow at the Institute for Systems Biology to further unravel the mechanisms underpinning microbe-host interaction. Outside of the lab, Nathaniel is an avid rock climber, dog walker, and partner to fellow scientist Dr. Minke Nota. More details and current position can be found at https://venkatesh.isbscience.org/

About Thomaz Bastiaanssen:

Dr. Thomaz Bastiaanssen is the lead bioinformatician in Prof. John F. Cryan’s microbiota-gut-brain axis group in Cork, Ireland. He is interested in the ecological dynamics governing host-microbe communication and how this complex interplay can impact human well-being. He will soon transition to a new role at Amsterdam UMC, the Netherlands, where he will continue to study the microbiome gut-brain axis. Besides working on multi-omics analyses, he enjoys horror stories, tabletop games and spending time with his wife, son, and corgi. His website can be found at: https://thomazbastiaanssen.github.io/