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Moody microbes or fecal phrenology: what do we know about the microbiota-gut-brain axis?

Forsythe P, Kunze W, Bienenstock J - BMC Med (2016)

Bottom Line: Given the state of the art in this exploding field and the hopes, as well as the skepticism, which have been engendered by its popular appeal, we explore recent examples of evidence in rodents and data derived from studies in humans, which offer insights as to pathways involved.Communication between gut and brain depends on both humoral and nervous connections.We offer critical and cautionary commentary on the available evidence, and identify gaps in our knowledge that need to be filled so as to achieve translation, where possible, into beneficial application in the clinical setting.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada. forsytp@mcmaster.ca.

ABSTRACT

Introduction: The microbiota-gut-brain axis is a term that is commonly used and covers a broad set of functions and interactions between the gut microbiome, endocrine, immune and nervous systems and the brain. The field is not much more than a decade old and so large holes exist in our knowledge.

Discussion: At first sight it appears gut microbes are largely responsible for the development, maturation and adult function of the enteric nervous system as well as the blood brain barrier, microglia and many aspects of the central nervous system structure and function. Given the state of the art in this exploding field and the hopes, as well as the skepticism, which have been engendered by its popular appeal, we explore recent examples of evidence in rodents and data derived from studies in humans, which offer insights as to pathways involved. Communication between gut and brain depends on both humoral and nervous connections. Since these are bi-directional and occur through complex communication pathways, it is perhaps not surprising that while striking observations have been reported, they have often either not yet been reproduced or their replication by others has not been successful.

Conclusions: We offer critical and cautionary commentary on the available evidence, and identify gaps in our knowledge that need to be filled so as to achieve translation, where possible, into beneficial application in the clinical setting.

No MeSH data available.


Related in: MedlinePlus

Hardwired connections between gut microbes and the brain: Gut microbes can modulate activity of spinal and vagal sensory neurons. Vagal sensory neuron may assume both primary afferent and interneuron functions via activation of enteric nervous system to vagal fiber nicotinic sensory synapse. Distinct bacterial species have been demonstrated to modulate neural activity through inhibition of the TRPV1 and KCa3.1 ion channels on spinal and intrinsic primary afferents respectively
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Fig2: Hardwired connections between gut microbes and the brain: Gut microbes can modulate activity of spinal and vagal sensory neurons. Vagal sensory neuron may assume both primary afferent and interneuron functions via activation of enteric nervous system to vagal fiber nicotinic sensory synapse. Distinct bacterial species have been demonstrated to modulate neural activity through inhibition of the TRPV1 and KCa3.1 ion channels on spinal and intrinsic primary afferents respectively

Mentions: The major afferent anatomical connections between the gut and the brain include vagal and spinal nerves, their ganglia and the spinal cord. However, within the gut, there are two types of sensory nerves; the extrinsic primary afferent neurons with somata outside the gut, and intrinsic primary afferent neurons (IPANs) with somata within the gut wall. Recent research has identified that certain bacteria and bacterial components in the lumen of the gut can modulate both extrinsic and intrinsic intestinal sensory systems, with consequences for peristalsis, nociception, brain chemistry and mood [10, 11, 17–19] (Fig. 2). Clearly, better knowledge of the neuronal projection pathways by which such signals reach the brain is critical to understanding the microbiota-gut-brain axis. It is also important to emphasize that communication in this axis is bi-directional, and there is strong evidence that, for example, stress has a significant effect on the composition and function of the gut microbiota [20–23].Fig. 2


Moody microbes or fecal phrenology: what do we know about the microbiota-gut-brain axis?

Forsythe P, Kunze W, Bienenstock J - BMC Med (2016)

Hardwired connections between gut microbes and the brain: Gut microbes can modulate activity of spinal and vagal sensory neurons. Vagal sensory neuron may assume both primary afferent and interneuron functions via activation of enteric nervous system to vagal fiber nicotinic sensory synapse. Distinct bacterial species have been demonstrated to modulate neural activity through inhibition of the TRPV1 and KCa3.1 ion channels on spinal and intrinsic primary afferents respectively
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4836158&req=5

Fig2: Hardwired connections between gut microbes and the brain: Gut microbes can modulate activity of spinal and vagal sensory neurons. Vagal sensory neuron may assume both primary afferent and interneuron functions via activation of enteric nervous system to vagal fiber nicotinic sensory synapse. Distinct bacterial species have been demonstrated to modulate neural activity through inhibition of the TRPV1 and KCa3.1 ion channels on spinal and intrinsic primary afferents respectively
Mentions: The major afferent anatomical connections between the gut and the brain include vagal and spinal nerves, their ganglia and the spinal cord. However, within the gut, there are two types of sensory nerves; the extrinsic primary afferent neurons with somata outside the gut, and intrinsic primary afferent neurons (IPANs) with somata within the gut wall. Recent research has identified that certain bacteria and bacterial components in the lumen of the gut can modulate both extrinsic and intrinsic intestinal sensory systems, with consequences for peristalsis, nociception, brain chemistry and mood [10, 11, 17–19] (Fig. 2). Clearly, better knowledge of the neuronal projection pathways by which such signals reach the brain is critical to understanding the microbiota-gut-brain axis. It is also important to emphasize that communication in this axis is bi-directional, and there is strong evidence that, for example, stress has a significant effect on the composition and function of the gut microbiota [20–23].Fig. 2

Bottom Line: Given the state of the art in this exploding field and the hopes, as well as the skepticism, which have been engendered by its popular appeal, we explore recent examples of evidence in rodents and data derived from studies in humans, which offer insights as to pathways involved.Communication between gut and brain depends on both humoral and nervous connections.We offer critical and cautionary commentary on the available evidence, and identify gaps in our knowledge that need to be filled so as to achieve translation, where possible, into beneficial application in the clinical setting.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada. forsytp@mcmaster.ca.

ABSTRACT

Introduction: The microbiota-gut-brain axis is a term that is commonly used and covers a broad set of functions and interactions between the gut microbiome, endocrine, immune and nervous systems and the brain. The field is not much more than a decade old and so large holes exist in our knowledge.

Discussion: At first sight it appears gut microbes are largely responsible for the development, maturation and adult function of the enteric nervous system as well as the blood brain barrier, microglia and many aspects of the central nervous system structure and function. Given the state of the art in this exploding field and the hopes, as well as the skepticism, which have been engendered by its popular appeal, we explore recent examples of evidence in rodents and data derived from studies in humans, which offer insights as to pathways involved. Communication between gut and brain depends on both humoral and nervous connections. Since these are bi-directional and occur through complex communication pathways, it is perhaps not surprising that while striking observations have been reported, they have often either not yet been reproduced or their replication by others has not been successful.

Conclusions: We offer critical and cautionary commentary on the available evidence, and identify gaps in our knowledge that need to be filled so as to achieve translation, where possible, into beneficial application in the clinical setting.

No MeSH data available.


Related in: MedlinePlus