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Sign In Create your free profile. Sections U. tv Today Nightly News MSNBC Meet the Press Dateline. Hsiao is one of the researchers leading the way in this field and her lab at UCLA has explored the part these microorganisms might play in everything from foetal brain development to cognition and neurological conditions such as epilepsy and depression.

She has also investigated how these microbes might be influencing our brains and thinking. We also find that under shorter timescales, gut microbes can regulate the production of biochemicals, like serotonin , that actively stimulate neuronal activity.

Indeed, research suggests our microbes may be communicating with our brains through numerous pathways , from immunity to biochemicals. Another candidate is the vagus nerve , which acts as the superfast "internet connection" between our brain and internal organs, including the gut.

The bacteria Lactobacillus rhamnosus JB1 , for example, appears to improve the mood of anxious and depressed mice. This beneficial effect is removed, however, when the signals travelling along the vagus nerve are blocked, suggesting it could be being used as a communication pathway by the bacteria.

William Beaumont's research on the digestive juices of Alexis St Martin gave some of the first hints of the interaction between our guts and brains Credit: Getty Images. Much of the research in this field is conducted in mice and other small animals.

And mice, of course, aren't humans. But given the mindboggling complexities of establishing causality between microbial signals and changes in human thought and behaviour, animal studies have provided some intriguing insights into the strange interactions between bacteria and brain.

Research, for example, shows that "germ-free" rats and mice those without any microbiota after being reared in sterile conditions are more prone to anxiousness , and less sociable than those with an intact microbiota. Germ-free mice, and those given antibiotics have also been found to be more hyperactive, prone to risky behaviour and less able to learn or remember.

Antibiotics, which can reduce the microbiota in an animal, also reduce shoaling behaviour in zebrafish , while probiotics boost it. Again, the human brain is vastly more complex than that of a rodent or fish, but they do share some similarities and can offer clues.

It makes sense that bacteria, wherever they live, might benefit from helping their hosts to be more sociable and less anxious. By interacting with other people, for example, we help our bacteria spread.

And whether or not they're really pulling our strings, it's in our microbes' evolutionary interests to make their environment as conducive to survival as possible.

But do communicative microbes, congregating zebrafish or friendly mice really matter? Hopefully, yes, say the researchers.

Ultimately, a better understanding of these processes could lead us towards ground-breaking new treatments for a range of mental health conditions. There are caveats, of course.

While some strains of bacteria appear to have a positive effect on the human mind, many others don't and researchers have yet definitively to establish why — and how.

Humans are also unfathomably complex, and when it comes to thinking and mental health, there are countless other factors at play, from genetics and personality to the environment around us. Disclaimers aside, however, more research could bring fresh hope.

Philip Burnet, an associate professor in the University of Oxford's department of psychiatry, notes that many mental health conditions have been associated with changes in the microbiota.

Often, this imbalance or "dysbiosis" is characterised by a reduced amount of certain bacteria, particularly those that produce short-chain fatty acids such as butyrate, which is widely believed to improve brain function when they break down fibre in the gut.

Indeed, a study by Mireia Valles-Colomer, a microbiologist at KU Leuven University of Leuven in Belgium at the time, and her colleagues found a correlation between the amount of these butyrate-producing bacteria and wellbeing.

Specifically, the researchers noted in the study that: "Butyrate-producing Faecalibacterium and Coprococcus bacteria were consistently associated with higher quality of life indicators. Together with Dialister , Coprococcus spp. were also depleted in depression, even after correcting for the confounding effects of antidepressants.

Antibiotics can change the shoaling behaviour of Zebrafish Credit: Getty Images. Human studies on the communication between the gut, the brain and the microbiota are still relatively few and far between.

And Burnet urges caution: "It is not known whether these altered levels in gut bacteria cause low mood or whether microbial numbers change because people who are depressed might modify their eating habits or eat less. Nevertheless, he has been exploring how prebiotics which encourage bacteria to grow and probiotics live bacteria might one day be used as psychobiotics to nurture populations of "good" bacteria — and treat a variety of mental health conditions.

For example, one study by Burnet, Rita Baião, a psychologist also at the University of Oxford, and their colleagues uncovered some particularly interesting findings. Although the study was funded by a company that manufactures probiotic bacteria, it used a randomised, double-blind, placebo-controlled trial — considered to be a gold standard study design during which neither participants nor researchers are aware whether they are receiving the treatment or not.

The researchers investigated the effect a multispecies probiotic might have on emotional processing and cognition in people with mild to moderate depression.

But the study also monitored their mood before and after the experiment using the Patient Health Questionnaire-9 PHQ-9 , which measures depression severity. Cognition was originally thought to be exclusively regulated by the central nervous system, with long-term potentiation and neurogenesis contributing to the creation and storage of memories, but now other systems, including, for example, the immune system and the intestinal microbiome may also be involved.

Cognitive impairment has been identified in numerous disease states, both gastrointestinal and extraintestinal in nature, many of which have also been characterized as having a role for dysbiosis in disease pathogenesis. This includes, but is not limited to, inflammatory bowel diseases, irritable bowel syndrome, type 1 diabetes, obesity, major depressive disorder, and autism spectrum disorder.

For example, your gut helps regulate appetite by telling the brain when it's time to stop eating. About 20 minutes after you eat, gut microbes produce proteins that can suppress appetite, which coincides with the time it often takes people to begin feeling full.

How might probiotics fit in the gut-brain axis? Some research has found that probiotics may help boost mood and cognitive function and lower stress and anxiety.

For example, a study published by Frontiers in Aging Neuroscience found that Alzheimer's patients who drank milk made with four probiotic bacteria species for 12 weeks scored better on a test to measure cognitive impairment compared with those who drank regular milk. And a small study reported in the journal Gastroenterology found that women who ate yogurt with a mix of probiotics twice a day for four weeks were calmer when exposed to images of angry and frightened faces compared to a control group.

MRIs also found that the yogurt group had lower activity in the insula, the brain area that processes internal body sensations, like those emanating from the gut.

They number in their trillions and include thousands of different species. Many of these microorganisms, including bacteria, archaea and eukarya, were here long before humans, have evolved alongside us and now outnumber our own cells many times over.

Indeed, as John Cryan, a professor of anatomy and neuroscience at University College Cork, rather strikingly put it in a TEDx talk : "When you go to the bathroom and shed some of these microbes, just think: you are becoming more human. Collectively, these microbial legions are known as the "microbiota" — and they play a well-established role in maintaining our physical health, from digestion and metabolism to immunity.

They also produce vital compounds the human body is incapable of manufacturing on its own. But what if they also had a hotline to our minds? In our new book, Are You Thinking Clearly?

And it turns out the microbes that call our bodies their home can have a surprising amount of control over our brains. Over the last few decades, researchers have started to uncover curious, compelling — and sometimes controversial — evidence to suggest that the gut microbiota doesn't just help to keep our brains in prime working order by helping to free up nutrients for it from our food, but may also help to shape our very thoughts and behaviour.

Their findings may even potentially bolster how we understand and lead to new treatments for a range of mental health conditions, from depression and anxiety to schizophrenia. The picture is still very far from complete, but in the wake of the Covid pandemic, which has had a deleterious impact on people's mental health in many parts of the world, unpicking this puzzle could be more important than ever.

One of the research field's key origin stories took place in the North American wilderness — and, be warned, it makes for some stomach-churning reading. The year was and a young trader named Alexis St Martin was loitering outside a trading post on what is now called Mackinac Island, in what is now Michigan, when a musket accidentally went off next to him, firing a shot into his side from less than a yard 91cm away.

His injuries were so bad that part of his lungs, part of his stomach and a good portion of his breakfast that day spilled out through the wound in his left side. Death seemed certain, but an army surgeon named William Beaumont rode to the rescue and saved St Martin's life, although it took the best part of a year and multiple rounds of surgery.

What Beaumont couldn't repair, however, was the hole in his patient's stomach. This persistent fistula would remain a grim and lasting legacy of the accident, but Beaumont wasn't one to pass up a good opportunity — however unpleasant.

Realising that the hole provided a unique window into the human gut, he spent years investigating the intricacies of St Martin's digestion.

Exactly how willing a volunteer St Martin was is open to debate as Beaumont employed him as a servant while conducting research on him — the murky arrangement almost certainly wouldn't be considered ethical today.

Among the findings Beaumont uncovered during his studies of St Martin's guts, however, included how they were affected by its owner's emotions, such as anger. Through this finding, Beaumont, who would go on to be lauded as the " father of gastric physiology ", had hit upon the idea of a "gut-brain axis" — that the gut and the brain aren't entirely independent of one another but instead interact, with one influencing the other and vice versa.

And now we know that the microorganisms within our gut make this process even more complex and remarkable. How exactly our microbiota might be influencing our mind is a growing, pioneering and still relatively novel field. But there have been advances over the last 20 years or so, particularly in animals.

And, slowly, a case is being built to suggest that these microorganisms aren't just a vital part of our physical selves, but also our mental and emotional selves, too.

But we need to frame things evolutionarily. It's important to remember that the microbes were here before humans existed, so we have evolved with these 'friends with benefits'. There has never been a time when the brain existed without the signals coming from the microbes.

And could we modulate these microbes therapeutically to improve thinking, behaviour and brain health? Hsiao is one of the researchers leading the way in this field and her lab at UCLA has explored the part these microorganisms might play in everything from foetal brain development to cognition and neurological conditions such as epilepsy and depression.

She has also investigated how these microbes might be influencing our brains and thinking. We also find that under shorter timescales, gut microbes can regulate the production of biochemicals, like serotonin , that actively stimulate neuronal activity.

Indeed, research suggests our microbes may be communicating with our brains through numerous pathways , from immunity to biochemicals. Another candidate is the vagus nerve , which acts as the superfast "internet connection" between our brain and internal organs, including the gut.

The bacteria Lactobacillus rhamnosus JB1 , for example, appears to improve the mood of anxious and depressed mice. This beneficial effect is removed, however, when the signals travelling along the vagus nerve are blocked, suggesting it could be being used as a communication pathway by the bacteria.

William Beaumont's research on the digestive juices of Alexis St Martin gave some of the first hints of the interaction between our guts and brains Credit: Getty Images.

Much of the research in this field is conducted in mice and other small animals. And mice, of course, aren't humans. Moreover, obvious alterations happen in the Firmicutes subgroups, with multiple members in this phylum decreasing in number. The proportions of facultative anaerobes, such as Staphylococcus and Bacillus , and Proteobacteria such as E.

Gut microbiota-based therapy seems a promising potential approach to be used in the prevention and future therapies for cognitive disorders. However, there are limited clinical studies and so many difficulties for extrapolation the results of animal models to humans including the differences in genomic sequences, gut microbiota composition, and dietary pattern.

Future large prospective studies are needed to shed light on the role of gut microbiota in the etiology of dementia and recommendations for clinical practice. An ethics statement is not applicable because this study is based exclusively on published literature. This study was supported by the National Institute for Medical Research Development Grant No.

This study was designed by H. and F. Data collection or processing was done by H. and P. Analysis or interpretation was performed by H. Literature search was done by H.

This study was written by H. All authors have read and approved the manuscript. This study is based exclusively on published literature, and all references are included in this article.

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Advanced Search. Skip Nav Destination Close navigation menu Article navigation. Volume 68, Issue Next Article. Statement of Ethics. Conflict of Interest Statement. Funding Sources. Author Contributions. Data Availability Statement.

Article Navigation. Systematic Review October 25 Is There Any Link between Cognitive Impairment and Gut Microbiota? Subject Area: Geriatrics and Gerontology. Pooneh Angoorani ; Pooneh Angoorani.

a Obesity and Eating Habits Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. This Site. Google Scholar. Hanieh-Sadat Ejtahed b Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

haniejtahed yahoo. Seyed Davar Siadat ; Seyed Davar Siadat. c Department of Mycobacteriology and Pulmonary Research, Microbiology Research Center, Pasteur Institute of Iran, Tehran, Iran.

d Elderly Health Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. sharifi gmail. Bagher Larijani Bagher Larijani. Gerontology 68 11 : — Article history Received:.

Cite Icon Cite. toolbar search Search Dropdown Menu. toolbar search search input Search input auto suggest. Journal Section:. The alterations in gut microbiota might lead to cognitive disorders.

Firmicutes and Bifidobacteria decrease in the elderly. The Proteobacteria increase throughout aging. Table 1. View large. View Large. Table 2. View large Download slide. The authors have no conflicts of interest to declare.

Search ADS. Different cognitive frailty models and health-and cognitive-related outcomes in older age: from epidemiology to prevention. World Health Organization. National Collaborating Centre for Mental Health; National Institute for Health and Clinical Excellence: Guidance.

Dementia: a NICE-SCIE guideline on supporting people with dementia and their carers in health and social care. Gut microbiota as a target in the pathogenesis of metabolic disorders: a new approach to novel therapeutic agents. Adaptation of human gut microbiota to bariatric surgeries in morbidly obese patients: a systematic review.

Our little friends with big roles: alterations of the gut microbiota in thyroid disorders. Probiotics function mechanistically as delivery vehicles for neuroactive compounds: microbial endocrinology in the design and use of probiotics.

This article corrects: gamma-Aminobutyric acid production by culturable bacteria from the human intestine. Metagenome analysis of bodily microbiota in a mouse model of Alzheimer disease using bacteria-derived membrane vesicles in blood.

Microbiome-metabolome signatures in mice genetically prone to develop dementia, fed a normal or fatty diet. Abnormal gut microbiota composition contributes to cognitive dysfunction in SAMP8 mice. CircNF improves the gut microbiome structure and function in AD-like mice.

Revisiting metchnikoff: age-related alterations in microbiota-gut-brain axis in the mouse. Gut microbiome composition is associated with age and memory performance in pet dogs. Effects of thymol on amyloid-β-induced impairments in hippocampal synaptic plasticity in rats fed a high-fat diet.

The association of post-stroke cognitive impairment and gut microbiota and its corresponding metabolites. Fecal microbiome among nursing home residents with advanced dementia and Clostridium difficile. Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly.

The relationship between the gut microbiome and mild cognitive impairment in patients without dementia: a cross-sectional study conducted in Japan.

Analysis of the relationship between the gut microbiome and dementia: a cross-sectional study conducted in Japan. Growing up in a bubble: using germ-free animals to assess the influence of the gut microbiota on brain and behavior.

Links between gut microbes and depression strengthened. Campylobacter jejuni infection increases anxiety-like behavior in the holeboard: possible anatomical substrates for viscerosensory modulation of exploratory behavior. Neonatal infection induces memory impairments following an immune challenge in adulthood.

Postnatal microbial colonization programs the hypothalamic pituitary adrenal system for stress response in mice.

Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. The probiotic Bifidobacteria infantis : an assessment of potential antidepressant properties in the rat.

Blood-brain barrier failure as a core mechanism in cerebral small vessel disease and dementia: evidence from a cohort study. Diversity, metabolism and microbial ecology of butyrate-producing bacteria from the human large intestine.

The human gut bacteria Bacteroides thetaiotaomicron and Fusobacterium varium produce putrescine and spermidine in cecum of pectin-fed gnotobiotic rats. Diabetes, Alzheimer disease, and vascular dementia: a population-based neuropathologic study.

Higher incidence of mild cognitive impairment in familial hypercholesterolemia. Diabetes and hypercholesterolemia increase blood-brain barrier permeability and brain amyloid deposition: beneficial effects of the LpPLA2 inhibitor darapladib. SSeCKS regulates angiogenesis and tight junction formation in blood-brain barrier.

Organ-specific protection mediated by cooperation between vascular and epithelial barriers. Gut microbiota composition correlates with diet and health in the elderly.