- how gut microbes communicate with the brain
- why imbalanced gut microbiota can lead to obesity and diabetes
- how harmful gut bacteria cause heart and liver disease.
Gut Microbiome – What Is It?
The collection of microbes (bacteria, fungi, viruses) living in our gut is called ‘gut microbiota’ or ‘gut microbiome’ .
In fact, less than half of the cells in the human body actually belong to the body itself. The rest are microbes.
Gut microbes play many beneficial roles in our bodies. They:
- help harvest more energy from food .
- provide nutrients such as vitamins B and K [1, 5].
- strengthen the gut barrier .
- strengthen the immune system .
- protect from harmful and opportunistic microbes [1, 5].
- process bile acids .
- degrade toxins and cancer-causing chemicals .
- are essential for the normal functioning of organs other than the gut, especially the brain, because they impact our mood and cognitive ability .
An imbalanced microbiota makes us more susceptible to infections, immune disorders, and inflammation .
Therefore, improving gut microbiota is a promising approach to combat a number of widespread diseases and disorders .
For ways to improve your gut bacteria check: Gut Microbiome: 16 Factors that can Improve or Worsen It
Composition of the Gut Microbiome
Humans harbor over 2,000 species of bacteria .
Most of the gut bacteria (80–90%) belong to two groups: Firmicutes and Bacteroidetes .
In the small intestine, the transit time is short and there are usually high levels of acids, oxygen, and antimicrobial agents. These all limit bacterial growth. Only fast-growing bacteria resistant to oxygen and able to strongly adhere to gut walls/mucus are able to survive .
In contrast, the colon has a dense and diverse community of bacteria. These use complex carbohydrates which are not digested in the small intestine .
Development and Aging of the Gut Microbiome
It was long thought that gut microbiota is established after birth. However, some research indicates that placenta may also have its own unique microbiome. Therefore, humans may be first colonized as fetuses .
At birth, the gut is colonized with microbes from both the mother and the environment. By the time humans reach one year of age, each individual develops a unique bacterial profile .
The adult-like structure of the gut microbiota occurs after the 3rd year of life .
However, in response to hormones in puberty, gut microbiota undergoes changes once again. This results in differences between males and females .
In adulthood, the composition of the gut microbiota is relatively stable. However, it can still be perturbed by life events .
In people over the age of 65, the microbial community shifts (with an increase of Bacteroidetes). Overall, bacterial metabolic processes, such as short-chain fatty acid (SCFA) production, are reduced, while the breakdown of proteins is increased .
Gut Microbiome Opens an Exciting New Chapter in Science
Science is only beginning to understand the many roles gut microbes play in our bodies. In fact, studies about gut bacteria are growing exponentially, and most of the research is recent.
There are a lot of questions that remain unanswered. However, we can look forward to a lot of new exciting breakthroughs in the years to come.
The number of studies related to ‘Gut Microbiota’, according to NCBI (https://www.ncbi.nlm.nih.gov/pubmed).
Ways In Which Gut Bacteria Influence Our Health
1) Produce Essential Vitamins
- vitamin B12
- folate/vitamin B9
- vitamin K
- riboflavin/vitamin B2
- biotin/vitamin B7
- nicotinic acid/vitamin B3
- pantothenic acid/vitamin B5
- pyridoxine/vitamin B6
- thiamine/vitamin B1
2) Produce SCFAs
These SCFAs have many important functions in the body:
- They provide ∼10% of the daily caloric requirement .
- They activate AMPK and stimulate weight loss .
- Propionate decreases fat build-up in the liver, lowers blood cholesterol, and increases the feeling of satiety .
- Acetate decreases appetite .
- Butyrate decreases inflammation and fights cancer .
- Acetate and propionate increase Treg cells , which curb excessive immune responses.
Diets with more fiber and less meat result in higher amounts of SCFAs .
3) Change Our Brains
Gut bacteria communicate with our brains. In fact, gut bacteria influence our behavior and cognitive function .
This communication runs both ways. Gut microbes and the brain influence each other, and we call this the gut-brain axis .
How do the gut and brain communicate?
- Via the vagus nerve and autonomic nervous system .
- Microbes release serotonin, GABA, acetylcholine, dopamine, and noradrenaline into the gut. Via the blood, some of these may enter the brain [18, 3].
- SCFAs, also produced by bacteria, are energy sources for nerve and glial cells in the brain .
- Via immune and inflammatory molecules .
Gut Bacteria Can Improve or Worsen Mood and Behavior
When gut microbiota is disturbed by infection or inflammation, this can decrease our mental wellbeing.
People with depression (46 subjects) had increased Bacteroidetes, Proteobacteria, and Actinobacteria and decreased Firmicutes (compared to 30 controls) .
In a TB-RCT with 40 healthy adults, probiotics reduced negative thoughts associated with a sad mood .
A study of 710 subjects showed that fermented food (high in probiotics) can decrease social anxiety in anxiety-prone people .
Interestingly, when rats receive human microbiota from depressed patients, they develop depression .
Interestingly, germ-free mice (mice without gut bacteria) had reduced anxiety. They had more serotonin in the brain (hippocampus). This altered behavior could be reversed by bacterial colonization only when the mice were still young. This shows that gut microbes also have an important role in brain development .
However, a large study of over 1 million people showed that in humans, treatment with a single antibiotic course increased the risk of depression. The risk increased even further with recurrent antibiotic use. A similar association was found for anxiety .
This shows that animal studies don’t always correspond to what we see in humans. However, both animal and human studies confirm that changes in gut microbiota influence our mood and can cause depression.
Gut Bacteria Can Improve or Worsen Cognitive Function
Diet can also affect cognitive function by changing gut microbiota. A western diet, high in saturated fats and added sugars, reduced Bacteroidetes, and increased Firmicutes and Proteobacteria in adult rodents. These changes are associated with cognitive impairments .
Transferring gut bacteria from western diet-fed mice to other mice increased their anxiety and impaired learning and memory .
4) Can Make You More or Less Susceptible to Stress
Your gut bacteria determines the way in which you react to stress. Our microbiome programs the hypothalamic-pituitary-adrenal (HPA) axis early in life. This, in turn, determines our reaction to stress later in life .
Germ-free mice have an exaggerated stress response (they have a hyperactive HPA axis). They also have lower BDNF, which is a factor involved in nerve cell survival. Bifidobacteria, when given to these mice early in life, restore the HPA axis to normal [18, 22].
‘Good bacteria’ (probiotics) can improve reaction to stress and associated disorders in humans.
5) Strengthen the Intestinal Barrier
The mucus in the gut acts as a lubricant and protects the gut wall from irritation. This layer is thinner in germ-free animals .
6) May Cause IBS
IBS also occurs after the use of antibiotics .
People with IBS have decreased microbial diversity and the gut microbiota is more unstable. There is a decreased amount of lactobacilli and bifidobacteria .
A high Firmicutes to Bacteroides ratio is found in some IBS patients, where it correlates with depression and anxiety .
A meta-analysis of 15 trials with 1793 subjects showed that probiotics improved symptoms in IBS .
Similarly, fecal transplant improved IBS in 58% of the 48 patients in the study .
7) Can Make You Fat or Thin
Obese people (and animals) have lower gut microbial diversity .
Two different studies, in 12 adults and 78 children, showed that obese subjects had less Bacteroidetes and more Firmicutes in the gut. They also had higher short-chain fatty acids (SCFAs), which are linked with the development of obesity. The proportion of Bacteroidetes increased on a low-calorie diet [44, 45].
A somewhat larger study in humans (154 subjects) confirmed that obesity was associated with :
- reduced levels of Bacteroidetes
- reduced bacterial density
- increased bacterial genes that metabolize sugars and fats for energy
Studies in mice and rats also confirmed the link between Bacteroidetes and leanness. Bacteroidetes are more abundant in lean animals, while Firmicutes are more abundant in their obese counterparts [47, 48, 49].
Obese mice have a 20:80 Bacteroidetes: Firmicutes ratio, while in lean animals it’s 40:60. The excess Firmicutes help the obese mice draw more calories from the ingested diet, leading to obesity .
A study of 436 mother-child pairs showed that exposure to antibiotics in pregnancy increased the risk of childhood obesity by 84% .
Early exposure of young mice to antibiotics makes them fatter .
‘Good bacteria’ that are decreased in obese people include:
8) May Improve Type 2 Diabetes
Gut microbiota may play a crucial role in the development of metabolic diseases .
A study of 345 subjects showed that diabetics had fewer butyrate-producers and more of opportunistic harmful bacteria .
Akkermansia muciniphila and Faecalibacterium prausnitzii are butyrate-producing beneficial bacteria. A study of 121 subjects showed that they were decreased in people with prediabetes and newly diagnosed type 2 diabetes .
In mice, probiotics C. butyricum and L. casei improve diabetes symptoms (fasting glucose, glucose tolerance, insulin resistance). Both bacteria decreased Firmicutes and increased Bacteroidetes and butyrate-producing bacteria [59, 60].
9) Imbalanced Gut Microbiota May Contribute to Heart Disease
Both human and animal studies suggest that gut bacteria contribute to the development of heart disease .
We know that patients with hardened arteries (atherosclerosis) have altered gut microbiota .
A study of 119 people showed that those with heart disease had more Firmicutes and less Bacteroidetes .
10) Are Important for Liver Health
People with fatty liver, have an increased prevalence of Firmicutes, similar to the bacterial imbalance seen in obesity .
In a study of 66 patients, Bifidobacterium longum, in addition to prebiotics and lifestyle modifications, improved fatty liver. The probiotic lowered AST (aspartate aminotransferase, a liver enzyme), TNF-α, CRP, and insulin resistance and reduced liver damage .
In mice, gut microbiota protects against liver injury and damage. Germ-free mice are more susceptible to toxin-induced liver damage .
Moreover, a probiotic mixture (VSL#3) was able to reduce liver injury in mice .
11) Are Important for Immunity
Our immunity is strongly connected to our gut. In fact, about 70% of our immune cells live in the gut .
During the first weeks and months of life, gut bacteria help infants gradually increase Th1 activity and restore the Th1/Th2 balance .
C-section-born infants have a delayed activation of Th1-type immunity. They have decreased Th1 responses due to altered gut microbiota .
Germ-free mice have fewer Treg cells and no Th17 cells. They have a Th1/Th2 imbalance which is biased toward the Th2 response .
12) Protect from Infections
Gut bacteria shield us from infection by :
- competing for nutrients with harmful bacteria
- producing by-products that inhibit the growth or activity of harmful bacteria
- maintaining the gut mucosal barrier
- stimulating innate and adaptive immunity
Stable microbiota also prevents the overgrowth of opportunistic microbes. For example, lactobacilli are important to prevent the overgrowth of Candida albicans .
Gut bacteria also help against parasites like malaria.
Just like people, some mice are more resistant to malaria infection than others. When germ-free mice received bacteria from “more resistant” mice, they also became more resistant. Their immune response was elevated and they had lower parasite numbers. Conversely, those that received bacteria from “susceptible” mice had higher parasite burdens .
Antibiotics often alter the gut microbiota, thereby reducing the resistance against harmful bacteria .
13) Suppress Inflammation
This can go either way, depending on the gut bacteria you have.
When gut microbiota is out of balance (gut dysbiosis), it can increase inflammation. This contributes to the development of chronic inflammatory diseases, such as IBD, multiple sclerosis, asthma and rheumatoid arthritis .
‘Good bacteria’ that seem to protect from inflammatory diseases include A. muciniphila and F. prausnitzii .
14) Protect from Allergies
Imbalanced gut microbiota increases the risk of allergies.
A study of 1879 subjects showed that people with allergies had lower gut microbial diversity. They had reduced Clostridiales (butyrate producers) and increased Bacteroidales .
These factors can both disturb gut microbiota and are associated with having food allergies :
- C-section delivery
- Lack of breast milk
- Antibiotics and gastric acid inhibitors
- Low fiber/ high-fat diet
Children exposed to farm environments have a lower risk of allergies. This is probably because they have a different microbial composition than those with other lifestyles .
Other protective factors against food allergies include having older siblings and pets. People with pets have more microbes in their home environment .
A study of 15,672 subjects showed that the use of antibiotics in pregnancy, as well as during the first months of life, increased the risk of cow’s milk allergy in infants (15,672 subjects) .
Two studies with 220 and 260 children showed that a probiotic Lactobacillus rhamnosus (LGG) accelerated the development of tolerance in infants with cow’s milk allergy. It also reduced the incidence of other allergies. This tolerance-inducing probiotic works by increasing butyrate-producing bacteria [86, 87, 88].
Finally, in a meta-analysis of 25 studies with 4031 infants, L. rhamnosus (LGG) lowered the risk of eczema .
15) Protect Against Asthma
In a study of 47 children, those with asthma had a lower diversity of gut bacteria as infants .
- Being breastfed
- Having multiple siblings
- Contact with farm animals and pets
- High-fiber diet
On the other hand, antibiotics increase the risk of asthma.
Two or more courses of antibiotics in pregnancy increased the risk of offspring asthma in 24,690 children .
Another study in 142 children showed that antibiotics early in life also increased the risk of asthma. They reduced bacterial richness, lowered Actinobacteria and increased Bacteroidetes. Reductions in bacterial richness persisted for more than 2 years after exposure .
A study (DB-RCT) with 137 infants showed that prebiotics reduce recurrent wheeze in allergy-prone children .
In mice, a high-fiber diet increased the ratio of Firmicutes to Bacteroidetes. This increased the levels of SCFAs and protected against airway inflammation .
Germ-free mice suffer from exaggerated allergic airway inflammation. Colonization with gut bacteria of young but not adult germ-free mice protected them from airway inflammation . This indicates there is a time-specific role gut bacteria play in the development of the immune system.
16) Imbalanced Gut Microbiota Contributes to IBD
Inflammatory bowel disease (IBD) is caused by a combination of genetic, environmental, and microbial factors. It manifests in the form of ulcerative colitis (UC) or Crohn’s disease (CD).
IBD can be directly associated with changes in the gut microbiota .
A meta-analysis of 9 studies with a total of 706 subjects showed that people with IBD generally have lower levels of Bacteroides .
Another meta-analysis (of 7 studies with 252 subjects) showed that people with IBD have more harmful bacteria, including E. coli and Shigella .
The anti-inflammatory drug mesalamine, used in IBD, decreases gut inflammation. It also decreases harmful Escherichia/Shigella abundance .
Interestingly, animals prone to IBD develop only minor inflammation when they are reared as germ-free .
Fusobacterium was also linked to colon cancer – and IBD is a recognized risk factor for colon cancer .
Faecalibacterium prausnitzii is an anti-inflammatory butyrate producer that may protect against IBD. It was decreased in patients with both ulcerative colitis and Crohn’s disease, in two studies of 214 and 13 subjects, respectively [99, 100].
17) Imbalanced Gut Microbiota Contributes to Autoimmune Diseases
Infants are less and less exposed to microbes. This can increase the risk of autoimmune disorders because it hampers the development of our immune system. The Treg cells are not produced properly, resulting in a loss of self-tolerance .
Short-chain fatty acids (SCFAs) produced by gut bacteria promote self-tolerance by increasing Treg cells .
Gut Bacteria in Type 1 Diabetes
A study of 8 children with type 1 diabetes found that they had a less stable and less diverse microbiome. They had less Firmicutes and increased Bacteroidetes . Basically, they had fewer butyrate producers.
Diabetes-prone mice treated with antibiotics were less likely to develop diabetes. In this case, antibiotics increased A. muciniphila. This is a beneficial bacterium that may have a protective role against autoimmune diabetes in infancy .
Diabetes-prone mice on fermentable fiber-rich diets were more likely to develop type 1 diabetes. This was correlated with more Bacteroidetes and less Firmicutes .
There is disagreement, however, of whether altered gut microbiota triggers the onset of type 1 diabetes, or is just a result of the disease .
Gut Bacteria in Lupus (SLE)
In a study of 40 subjects, patients with lupus had increased Bacteroides and decreased Firmicutes .
Lactobacillus improved kidney function in female mice with lupus-induced kidney inflammation. This treatment also prolonged their survival. Lactobacillus decreased inflammation by skewing the Treg/Th17 balance towards Treg. It decreased IL-6 and increased IL-10. This positive effect was not observed in males, suggesting a hormone dependency .
Lupus-prone mice develop different gut microbiota when they drink acidic water. They have more Firmicutes and less Bacteroidetes. These mice also have lower levels of lupus-associated antibodies and a slower progression of the disease .
Gut Bacteria in Multiple Sclerosis
Mice with experimental autoimmune encephalomyelitis (EAE, a mouse equivalent of MS) have disturbed gut microbiota. Antibiotics help make the disease less severe and reduce mortality .
Also, germ-free mice only develop a milder form of the disease. This is attributed to the impaired production of Th17 cells .
When germ-free mice are colonized with bacteria that increase Th17 they develop EAE. On the other hand, colonization with B. fragilis (beneficial bacterium) protects from EAE by increasing Treg cells [109, 110].
Gut Bacteria in Rheumatoid Arthritis
Environmental factors are much more important in the development of rheumatoid arthritis (RA) than genes . These factors include the gut microbiota.
Patients with RA have reduced gut microbial diversity. In a study of 72 subjects, the disturbance in gut microbiota was proportional to disease duration and autoantibody levels .
A study of 212 subjects showed that anti-rheumatic drugs could reverse the perturbations of gut bacteria in RA patients .
Several bacteria have been linked specifically to the development of RA. These include Prevotella copri, Collinsella, and Lactobacillus salivarius. They are all increased in RA patients [113, 114, 115].
On the other hand, another bacteria, Prevotella histicola, reduces the incidence and severity of arthritis in mice. P. histicola does this by increasing Tregs and IL-10 and reducing Th17 responses .
Germ-free animal studies are conflicting. Arthritis-prone mice do not develop arthritis when they are reared as germ-free. In contrast, germ-free rats develop more severe arthritis . Still, we can’t deny that gut microbiota plays a role in the disease.
Probiotics were shown to improve symptoms in patients with RA in several clinical trials (L. casei in a DB-RCT of 46 patients; L. acidophilus, L. casei and B. bifidum in a DB-RCT of 60 patients; Bacillus coagulans in 45 patients) [117, 118, 119].
18) May Increase Bone Strength
Our gut microbiota also communicates with our bones. However, this association was so far only studied in animals.
Germ-free mice had increased bone mass. It returned back to normal when these mice received gut bacteria from conventionally raised mice .
Furthermore, antibiotics increased bone density in young mice .
Probiotics, mainly lactobacilli, increased bone production and bone strength in animals .
19) Imbalanced Gut Microbiota May Contribute to Autism
Up to 70% of patients with autism also have gut-related symptoms. These include stomach pain, increased intestinal permeability, and an altered gut microbiome. This basically indicates that there is a disturbance of the gut-brain axis in autism [18, 3].
A small clinical trial involving 18 autistic children attempted a microbiota transfer therapy. It consisted of a 2-week antibiotic treatment, a bowel cleanse, and a fecal microbiota transplant. These children had 80% reduced gut-associated symptoms (constipation, diarrhea, indigestion, and stomach pain). Behavioral symptoms were also improved. The improvements persisted 8 weeks after the treatment ended .
Germ-free mice have impaired social skills. They exhibit excessive self-grooming (similar to repetitive behaviors in humans) and are more likely to spend time within an empty chamber or with an object than with another mouse. If these mice are colonized with gut bacteria after weaning, some but not all symptoms improve. This indicates that there is a critical time during infancy when gut bacteria impacts brain circuits [3, 18].
Antibiotics administered to rat mothers decreased offspring social interactions and increased anxiety .
When mice moms are fed a high-fat diet, their gut microbiota gets imbalanced, and their pups have social deficits. Co-housing and subsequent sharing of bacteria with the pups of lean mothers can correct these social impairments. Also, a single probiotic species, Lactobacillus reuteri, can improve these social deficits .
Another probiotic, Bacteroides fragilis, remodels the gut microbiome in mice. It also improves communication, repetitive and anxiety-like behaviors. However, it can’t correct social deficits .
20) Imbalanced Gut Microbiota May Contribute to Alzheimer’s
Germ-free mice are partially protected against the disease. Colonization of these mice with bacteria from diseased mice promotes Alzheimer’s development (non-peer reviewed study) .
The protein that forms amyloid plaques in Alzheimer’s is produced by gut bacteria. E. coli and Salmonella enterica are among the many bacteria that release amyloid proteins and can contribute to Alzheimer’s .
People with imbalanced microbiota are more likely to develop Alzheimer’s:
- Chronic fungal infection may increase the risk of Alzheimer’s [130, 131].
- Rosacea patients have a disturbed gut microbiome . They are at increased risk of developing dementia, particularly Alzheimer’s (study of 5,591,718 subjects) .
- People with diabetes may have double the risk of developing Alzheimer’s (study of 1,017 elderly subjects) .
21) Imbalanced Gut Microbiota May Contribute to Parkinson’s
A study of 144 subjects showed that patients with Parkinson’s disease have altered gut microbiota. Prevotellaceae are reduced by almost 80%. Enterobacteriaceae are increased and associated with greater postural instability and gait difficulty .
Parkinson’s-prone mice have fewer motor abnormalities when they are raised germ-free. If they are colonized with bacteria or given SCFAs, the symptoms get worse. Conversely, antibiotics help improve the disease .
If these germ-free mice receive gut bacteria from a patient with Parkinson’s, their symptoms get much worse .
22) Imbalanced Gut Microbiota Can Cause Colon Cancer
A study of 179 subjects showed that patients with colorectal cancer have an increased ratio of Bacteroides/Prevotella .
Another study of 27 subjects showed that people with colon cancer had more acetate and fewer butyrate producers .
Infections and harmful bacteria disturb gut microbiota and increase the risk of colon cancer:
- Infection with Streptococcus bovis is a risk factor for developing colon cancer (meta-analysis, 24 studies) .
- E. coli enhances tumor growth in mice with gut inflammation .
Cancer-prone mice have a reduced tumor load when they are raised as germ-free .
However, when germ-free mice receive bacteria from colon tumor-bearing mice, they develop larger tumors, while antibiotics slow down tumor growth .
23) Imbalanced Gut Microbiota is Associated with Chronic Fatigue Syndrome
Similarly, in a study of 87 subjects, patients with chronic fatigue syndrome had decreased bacterial diversity. In particular, there was a reduction of Firmicutes. There were more inflammatory and less anti-inflammatory species .
In a pair of monozygotic twins, the twin with chronic fatigue syndrome had lower microbial diversity compared to the unaffected sibling .
A study of 20 subjects showed that exercise caused a further disturbance in gut bacteria in people with chronic fatigue syndrome. This may explain the profound post-exertional malaise in those affected .
24) May Decrease Fatigue and Improve Athletic Performance
In animals, gut microbiota improved performance and reduced fatigue during exercise .
Germ-free mice have shorter endurance swimming time .
25) Influence Aging
Aging is often associated with disturbances in gut microbiota .
Elderly people tend to have an overall low diversity of gut bacteria. They have a very low abundance of Firmicutes and increased Bacteroidetes .
Gut dysbiosis causes low-grade chronic inflammation. It is also associated with a decline in immune system function (immunosenescence). Both of these accompany many aging-associated diseases .
People who age better may have better gut bacteria.
Germ-free mice live longer. Co-housing germ-free mice with old, but not young mice increased inflammatory cytokines in the blood .
26) May Help Maintain Circadian Rhythms
In mice, Bacteroidetes fluctuate during the day, while Firmicutes vary only slightly .
27-33) Other Conditions Possibly Associated with Imbalanced Gut Microbiota
Studies have also found links between gut bacteria and other disorders and diseases. These include:
- Ankylosing spondylitis [97, 160, 161, 162, 163]
- Schizophrenia 
- Eating disorders: anorexia nervosa, bulimia, and binge eating disorder [22, 165]
- Kidney disease [166, 167]
- Psoriasis 
- Urticaria 
- Acne 
For ways to improve your gut bacteria check: Gut Microbiome: 16 Factors that can Improve or Worsen It
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