Gut microbiota by-products circulate in the bloodstream, regulating host physiological

processes including immunity, metabolism and brain functions. Scientists from the Institut
Pasteur (a partner research organisation of Université Paris Cité), Inserm and the CNRS
have discovered that hypothalamic neurons in an animal model directly detect variations in
bacterial activity and adapt appetite and body temperature accordingly. These findings
demonstrate that a direct dialog occurs between the gut microbiota and the brain, a
discovery that could lead to new therapeutic approaches for tackling metabolic disorders
such as diabetes and obesity. The findings are due to be published in Science on April 15,
2022.

The gut is the body's largest reservoir of bacteria. A growing body of evidence reveals the
degree of interdependence between hosts and their gut microbiota, and emphasizes the
importance of the gut-brain axis. At the Institut Pasteur, neurobiologists from the Perception
and Memory Unit (Institut Pasteur/CNRS)[1], immunobiologists from the Microenvironment
and Immunity Unit (Institut Pasteur/Inserm), and microbiologists from the Biology and
Genetics of the Bacterial Cell Wall Unit (Institut Pasteur/CNRS/Inserm)[2] have shared their
expertise to investigate how bacteria in the gut directly control the activity of particular
neurons in the brain.

The scientists focused on the NOD2 (nucleotide oligomerization domain) receptor which is
found inside of mostly immune cells. This receptor detects the presence of muropeptides,
which are the building blocks of the bacterial cell wall. Moreover, it has previously been
established that variants of the gene coding for the NOD2 receptor are associated with
digestive disorders, including Crohn's disease, as well as neurological diseases and mood
disorders. However, these data were insufficient to demonstrate a direct relationship
between neuronal activity in the brain and bacterial activity in the gut. This was revealed by
the consortium of scientists in the new study.

Using brain imaging techniques, the scientists initially observed that the NOD2 receptor in
mice is expressed by neurons in different regions of the brain, and in particular, in a region
known as the hypothalamus. They subsequently discovered that these neurons' electrical
activity is suppressed when they come into contact with bacterial muropeptides from the gut.
"Muropeptides in the gut, blood and brain are considered to be markers of bacterial
proliferation," explains Ivo G. Boneca, Head of the Biology and Genetics of the Bacterial Cell
Wall Unit at the Institut Pasteur (CNRS/Inserm). Conversely, if the NOD2 receptor is absent,
these neurons are no longer suppressed by muropeptides. Consequently, the brain loses
control of food intake and body temperature. The mice gain weight and are more susceptible
to developing type 2 diabetes, particularly in older females.

In this study, the scientists have demonstrated the astonishing fact that neurons perceive
bacterial muropeptides directly, while this task was thought to be primarily assigned to
immune cells. "It is extraordinary to discover that bacterial fragments act directly on a brain
center as strategic as the hypothalamus, which is known to manage vital functions such as
body temperature, reproduction, hunger and thirst," comments Pierre-Marie Lledo, CNRS
scientist and Head of the Institut Pasteur's Perception and Memory Unit.

The neurons thus appear to detect bacterial activity (proliferation and death) as a direct
gauge of the impact of food intake on the intestinal ecosystem. "Excessive intake of a
specific food may stimulate the disproportionate growth of certain bacteria or pathogens,
thus jeopardizing intestinal balance," says Gérard Eberl, Head of the Microenvironment and
Immunity Unit at the Institut Pasteur (Inserm).

The impact of muropeptides on hypothalamic neurons and metabolism raises questions on

their potential role in other brain functions, and may help us understand the link between
certain brain diseases and genetic variants of NOD2. This discovery paves the way for new
interdisciplinary projects at the frontier between neurosciences, immunology and
microbiology, and ultimately, for new therapeutic approaches to brain diseases and
metabolic disorders such as diabetes and obesity.

[1] This research unit is also known as the "Genes, Synapses and Cognition Laboratory"
(Institut Pasteur/CNRS). Paris Brain Institute (CNRS/Inserm/Sorbonne Université/AP-HP)
also contributed to these findings.

[2] The CNRS unit's name is the "Integrative and Molecular Microbiology Unit" and the
Inserm unit's name is the "Host-Microbe Interactions and Pathophysiology Unit" (Institut
Pasteur/CNRS/Inserm).

Why did you choose this article?

I chose this article because I am interested in knowing how exactly does the digestive system
interact with the brain. There has been correlation between the

What did you learn from this article?

…That our mental state can be affected by microbiomes, a rather versatile and unstable
component for digestion and that the digestive system should be paid more attention to.
Besides, I used to think that our mental state affects many parts of organ function. Turns out
when it comes to the gut, it could be the other way round.For instance, if a person has
Irritable Bowel Syndrome and has mental disorders such as anxiety, it could be the imbalance
of microbiomes that causes the syndrome, and therefore cause anxiety.

Do you agree with all the information in the article? Why?

I mostly agree with the article’s message.However, given that such experiments are mostly
done using the mice as a simulation, I believe that the situation in the human brain might be
slightly different.

What is the importance of the issue?

Now that we know the mechanism for how the gut microbiota affects the brain’s ability to
control eating and regulate body temperature, more questions are raised about how
microbiota might affect other brain functions, and how individual patients could alleviate
their metabolic, and possibly mental disorders by focusing on treating microbiota instead.
What research can be done to help us understand more about the issue?

Some case studies on the patients who suffer from metabolic disorders, and
collect their samples which contain gut bacteria

How may you contribute to the issue?

Not over consume a specific type of food, have a varied and healthy diet to further reduce
risk for metabolic disorders
The COVID-19 pandemic has disrupted the lives of people who use drugs
in ways that hurt their mental health and changed drug use behaviors,
increasing their risk for overdose, according to surveys and interviews with
individuals in rural Illinois captured in a new study in Addiction Science and
Clinical Practice.

Drug overdoses have soared during the COVID-19 pandemic, with U.S. overdose deaths topping
100,000 during the 12-month period ending in April 2021. Researchers are beginning to untangle
how the pandemic and strategies for preventing the spread of the virus, such as stay-at-home
orders, may have contributed to this increase in deaths, from interruptions to harm reduction
programs to isolation and worsening mental health.
People who use drugs and live in rural areas may be disproportionately impacted by changes
brought on during the pandemic, given that many rural areas have higher rates of opioid and
methamphetamine use and already have limited drug treatment and harm reduction services.
People who use drugs in rural areas may also experience higher levels of stigma about their drug
use, which may contribute to a greater likelihood of using drugs alone and a reluctance to seek
medical care.
In a series of surveys and interviews with people who use drugs in rural southern Illinois, the
researchers sought to understand their experiences during the COVID-19 pandemic and how
disruptions at the structural and community level could affect individuals' overdose risk. Between
August 2020 and May 2021, the researchers conducted surveys with 50 individuals who use
opioids (without a prescription) or inject drugs, and did in-depth interviews with a subset of 17
participants.
"We know that there has been a tragic increase in overdose deaths during the pandemic. Our
study provides insight into why and how there have been more overdose deaths," said Suzan
Walters, research assistant professor at NYU School of Global Public Health and a researcher
with NYU's Center for Drug Use and HIV/HCV Research (CDUHR).
Not unlike the general population, people who use drugs reported worsened economic conditions
-- in a region already afflicted by widespread poverty -- and mental health during the pandemic.
Only 38 percent of participants felt confident that they could maintain a stable income during the
pandemic, thanks to layoffs, disruptions to their work in service industries, and fewer available
jobs. Moreover, participants reported that the pandemic exacerbated housing and food
insecurity.
A significant proportion of participants reported that their mental well-being had suffered: three-
quarters of the survey respondents felt more anxious or on edge during the pandemic, more than
half felt more depressed, and nearly half felt lonelier. Anxiety and depression are associated with
increased substance use, which in turn can increase the risk for overdose.
Participants also described how the pandemic changed their everyday drug use behaviors. Two-
thirds of survey respondents said the process of getting drugs was more difficult during the
pandemic, and over half worried that in the near future they would end up with a bad batch of
drugs that would be dangerous. Notably, half of the survey respondents said they were currently
more likely to use drugs alone than prior to the pandemic, which can increase overdose risk.
The interviews unearthed an emerging trend of consuming fentanyl "beans" or "buttons," which
were described as little capsules full of fentanyl. Participants said that fentanyl was cheaper and
more readily available than heroin, which became more difficult to obtain during the pandemic.
"Our findings suggest that structural and community issues during the pandemic increased
anxiety, depression, and loneliness on the individual level. Drug use patterns also changed, with
many talking about fear of fentanyl and increased access to it. All of these factors are likely to
increase overdose risk," said Walters, who is also an affiliated faculty at NYU Langone's Center
for Opioid Epidemiology and Policy (COEP).
To prevent overdoses, the researchers recommend not only ensuring access to resources and
services at the individual level, but also addressing larger systemic and community issues,
including greater access to economic opportunities and reducing stigma related to drug use.
Additional study authors include Rebecca Bolinski, Stacy Grundy, and Wiley Jenkins of Southern
Illinois University; Ellen Almirol, John Schneider, and Mai Pho of the University of Chicago; Scott
Felsher of the Community Action Place, Inc.; Samuel Friedman of CDUHR and NYU Grossman
School of Medicine; Lawrence Ouellet of the University of Illinois Chicago; and Danielle Ompad
of CDUHR and NYU School of Global Public Health. The work was funded by the NIH Clinical
and Translational Science Awards Program (UL1TR001445) and National Institute on Drug
Abuse (K01DA053159, P30DA01104, T32 DA007233-31, R25DA026401, 4UH3DA044829-03).

What did you learn from this article?

…That our mental state can be affected by microbiomes, a rather versatile and unstable
component for digestion and that the digestive system should be paid more attention to.
Besides, I used to think that our mental state affects many parts of organ function. Turns out
when it comes to the gut, it could be the other way round.For instance, if a person has
Irritable Bowel Syndrome and has mental disorders such as anxiety, it could be the imbalance
of microbiomes that causes the syndrome, and therefore cause anxiety.

Do you agree with all the information in the article? Why?

I mostly agree with the article’s message.However, given that such experiments are mostly
done using the mice as a simulation, I believe that the situation in the human brain might be
slightly different.

What is the importance of the issue?

Now that we know the mechanism for how the gut microbiota affects the brain’s ability to
control eating and regulate body temperature, more questions are raised about how
microbiota might affect other brain functions, and how individual patients could alleviate
their metabolic, and possibly mental disorders by focusing on treating microbiota instead.

What research can be done to help us understand more about the issue?

Some case studies on the patients who suffer from metabolic disorders, and
collect their samples which contain gut bacteria

How may you contribute to the issue?

Not over consume a specific type of food, have a varied and healthy diet to further reduce
risk for metabolic disorders