We share our bodies with our gut microbes. In fact, you could even say that a lot of what we are depends on the bacteria we carry. They can make us thin or fat, healthy or sick, happy or depressed. Science is just beginning to understand all the ways in which gut microbes affect our lives. In this post, we review what is known about gut bacteria so far, including the ways in which they are shaping our bodies and our minds. Read on to find out:
- 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
The collection of microbes (bacteria, fungi, viruses) living in our gut is called ‘gut microbiota’ or ‘gut microbiome’ .
In fact, there are likely more bacterial cells than human cells in and on the human body.
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: 15 Factors that can Improve or Worsen It
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 that are not digested in the small intestine .
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, the 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 again, 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 .
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).
- 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
These SCFAs are believed to have many important functions in the body:
- They provide about 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 is inversely related to 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 .
Gut bacteria communicate with our brains. In fact, researchers increasingly believe that the gut bacteria have a broad influence on both our behavior and cognitive function .
This communication runs both ways. Gut microbes and the brain influence each other; 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 .
When gut microbiota is disturbed by infection or inflammation, some researchers have argued that this can decrease our mental wellbeing. People with gut inflammatory diseases frequently also have depression and/or anxiety [19, 20].
People with depression (46 subjects) had increased Bacteroidetes, Proteobacteria, and Actinobacteria and decreased Firmicutes (compared to 30 controls) .
In a study of 40 healthy adults, probiotics reduced negative thoughts associated with a sad mood .
In a study of 710 subjects, fermented food (high in probiotics) decreased social anxiety in anxiety-prone people .
Interestingly, when rats received human microbiota from depressed patients, they developed depressive symptoms .
Interestingly, germ-free mice (mice without gut bacteria) had reduced anxiety and more serotonin in the brain (hippocampus). This altered behavior could be reversed by bacterial colonization only when the mice were still young. This result suggests 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 rates of depression. The association was even stronger 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, in both animal and human studies, changes in the gut microbiota influenced mood and mental health.
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 .
The gut bacteria is believed to influence the way in which humans 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.
The mucus in the gut acts as a lubricant and protects the gut wall from irritation. This layer is thinner in germ-free animals .
According to one study, postinfection IBS arises in 10% – 30% of patients who experience a bout of gut infection or inflammation. It is a condition associated with changes in the gut microbiota [38, 39].
IBS may also occur after a course of antibiotics .
People with IBS have decreased microbial diversity, and their gut microbiota tends to be less stable. They also tend to have a decreased amount of Lactobacilli and Bifidobacteria .
A high Firmicutes to Bacteroidetes 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 .
IBD has been linked to 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 a larger share of 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 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 [47, 48].
Obese people (and animals) have lower gut microbial diversity .
In two different studies, of 12 adults and 78 children, obese subjects had fewer Bacteroidetes and more Firmicutes in the gut. They also had more short-chain fatty acids (SCFAs), which may be linked with the development of obesity. The proportion of Bacteroidetes increased on a low-calorie diet [49, 50].
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 were more abundant in lean animals, while Firmicutes were more abundant in their obese counterparts [52, 53, 54].
Obese mice have a 20:80 Bacteroidetes to Firmicutes ratio, while lean animals tend toward 40:60. The excess Firmicutes may encourage the obese mice’s draw to more calories from the ingested diet, leading to obesity .
Early exposure of young mice to antibiotics made them fatter .
‘Good bacteria’ that are decreased in obese people include:
Some researchers have argued that the gut microbiota may play a crucial role in the development of metabolic diseases like diabetes .
A study of 345 subjects showed that diabetics had fewer butyrate producers and more 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 improved diabetes symptoms (fasting glucose, glucose tolerance, insulin resistance). Both bacteria decreased Firmicutes and increased Bacteroidetes and butyrate-producing bacteria [64, 65].
Both human and animal studies suggest that gut bacteria may contribute to the development of heart disease .
Patients with hardened arteries (atherosclerosis) tend to have altered gut microbiota .
A study of 119 people showed that those with heart disease had more Firmicutes and fewer Bacteroidetes .
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 .
Our immunity is strongly connected to our gut. In fact, about 70% of our immune cells live in the gut .
Some researchers believe that, during the first weeks and months of life, the 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 .
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
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 .
When gut microbiota is out of balance (gut dysbiosis), inflammation may increase. Some researchers believe that this process 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 .
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 are less likely to develop allergies. Researchers have argued that children who live on farms have a different microbial composition than those with other lifestyles, and their microbes protect them from allergic reactions .
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 rate of development of cow’s milk allergy in infants .
In two studies of 220 and 260 children, 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 [91, 92, 93].
Finally, in a meta-analysis of 25 studies with 4031 infants, L. rhamnosus (LGG) reduced the incidence of eczema .
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, two or more courses of antibiotics in pregnancy increased relative rates of offspring asthma in 24,690 children .
Another study in 142 children showed that antibiotics early in life also promoted the development of asthma. They reduced bacterial richness, lowered Actinobacteria and increased Bacteroidetes. Reductions in bacterial richness persisted for more than 2 years after exposure .
In one study of 137 allergy-prone children, prebiotics reduced recurrent wheeze .
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.
In the modern, sterile environment, infants are less and less exposed to microbes. Some researchers believe that this sterility could increase the rate of autoimmune disorders because it hampers the development of our immune system. They argue that, in the absence of exposure to beneficial bacteria, 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 .
A study of 8 children with type 1 diabetes found that they had a less stable and less diverse microbiome than healthy peers. They had fewer Firmicutes and increased Bacteroidetes . Overall, 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 .
In a study of 40 subjects, patients with lupus had increased Bacteroidetes 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 fewer Bacteroidetes. These mice also have lower levels of lupus-associated antibodies and a slower progression of the disease .
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 were colonized with bacteria that increase Th17 they developed EAE. On the other hand, colonization with B. fragilis (beneficial bacterium) protects from EAE by increasing Treg cells [109, 110].
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 improved 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].
The gut microbiota may also communicate in some way with the skeletal system. However, this association has so far only been 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 .
Up to 70% of patients with autism also have gut-related symptoms, including stomach pain, increased intestinal permeability, and an altered gut microbiome. This association has led some researchers to conclude 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, bowel cleanse, and 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 for 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. According to some researchers, this result indicates that there is a critical time during infancy when the gut microbiome impacts brain circuits [3, 18].
Antibiotics administered to rat mothers decreased offspring social interactions and increased anxiety .
When mouse mothers 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, remodeled the gut microbiome in mice. It also improved communication, repetitive and anxiety-like behaviors. However, it can’t correct social deficits .
Germ-free mice are partially protected against Alzheimer’s 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 .
In humans, imbalances in the gut microbiome are associated with Alzheimer’s:
- Chronic fungal infection may be associated with Alzheimer’s [130, 131].
- Rosacea patients have a disturbed gut microbiome . They developed dementia, particularly Alzheimer’s, at a significantly increased rate (study of 5,591,718 subjects) .
- People with diabetes may develop Alzheimer’s at twice the rate of those without (study of 1,017 elderly subjects) .
A study of 144 subjects showed that patients with Parkinson’s disease tend to 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 .
A study of 179 subjects showed that patients with colorectal cancer tend to 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 are linked to colon cancer:
- Infection with Streptococcus bovis is considered a risk factor for developing colon cancer (meta-analysis, 24 studies) .
- E. coli enhanced tumor growth in mice with gut inflammation .
Cancer-prone mice had a reduced tumor load when they are raised as germ-free .
However, when germ-free mice received bacteria from colon tumor-bearing mice, they developed larger tumors, while antibiotics slowed tumor growth .
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 .
In animals, certain gut microbiota improved performance and reduced fatigue during exercise .
Germ-free mice had shorter endurance swimming time .
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 .
Germ-free mice live longer. Co-housing germ-free mice with old, but not young mice increased inflammatory cytokines in the blood .
In mice, Bacteroidetes fluctuate during the day, while Firmicutes vary only slightly .
Studies have also found links between gut bacteria and other disorders and diseases. These include:
- Ankylosing spondylitis [45, 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: 15 Factors that can Improve or Worsen It