The probiotic formulation (PF) consisting of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 have been found to decrease stress-induced gastrointestinal discomfort. In this experiment, rats and human volunteers were tested. Rats were administered the PF formula for 2 weeks and tested in a conditioned defensive burying test, a screen model for anti-anxiety agents. In clinical trials, volunteers were randomly assigned to double-blind, placebo-controlled groups with PF administered for 30 days and assesed with a variety of tests: the Hopkins Symptoms Checklist, the Hospital Anxiety and Depression Scale, the Perceived Stress Scale, the the Coping Checklist and and 24 hour urinary free cortisol.

It was found that daily subchronic administration of PF significantly reduced anxiety-like behavior in rats and allieviated stress in volunteers. L. helveticus R0052 and B. longum R0175 taken together reduce anxiety-like behavior in rats and beneficial psychological effects in human volunteers.

Messaoudi, Michaël, et al. "Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects." British Journal of Nutrition 105.5 (2011): 755-764. 

Gut microbiota composition is associated with newborn functional brain connectivity and behavioral temperament  

Little is known about the gut microbiome, but it appars to play a role in human behavior and development. In this study, researchers look at how variability in the gut microbiome affects infant development of the brain. Infant gut microbiome diversity was measured using fecal samples and infant functional brain network connectivity was assessed using a resting state functional near infrared spectroscopy (rs-fNIR). The results show that micriobiome diversity is linked to individual variability in network connectivity and causes differences in their behavioral temperment. Data also corroborates that increases biodiversity of microbiota in the gut is associated with frontal-parietal connectivity, which has been linked to positive mental health.

Kelsey, Caroline M., et al. "Gut microbiota composition is associated with newborn functional brain connectivity and behavioral temperament." Brain, Behavior, and Immunity 91 (2021): 472-486.

Gut microbiota regulates maturation of the adult enteric nervous system via enteric serotonin networks  

The enteric nervous system (ENS) plays a vital role in gastrointestinal physiologic functions such as motility, fluid secretion, and blood flow. The gut consists of countless types of microbacteria that modulate host production of several signaling serationin (5-HT) and other hormones and neurotransmitters. 90% of 5-HT comes from the intestines, and 5-HT activation in the ENS has been linked to adult neurogenesis and neuroproduction. Results found that germ-free mice with a microbiota from normal mice modified neuroanatomy of the ENS, which is associated with the effects of 5-HT in the adult intestine. Modification of the 5-HT receptors and depletion of 5-HT have identified a link between gut microbiota and maturation of the ENS through 5-HT activation it's respectivce receptor. In conclusion, it was found that gut microbiota modulate the ENS anatomy via seratonin (5-HT) receptors.

De Vadder, Filipe, et al. "Gut microbiota regulates maturation of the adult enteric nervous system via enteric serotonin networks." Proceedings of the National Academy of Sciences 115.25 (2018): 6458-6463.

Substantial Production of Dopamine in the Human Gastrointestinal Tract

Large amounts of dopamine metabolites found in urinary excretion suggest that mass amounts of dopamine are produced from unknown locations in the body. In this experiment, the contribution of dopamine from mesenteric organs in humans was assesed via the plasma concentration of dopamine and its metabolites from blood samples.

It was found that mesenteric organs produce roughly 50% of dopamine formed in the body, most of which is unlikely to have came from sympathetic nerves, but another nonneuronal dopimengeric system.

Eisenhofer, Graeme, et al. "Substantial production of dopamine in the human gastrointestinal tract." The Journal of Clinical Endocrinology & Metabolism 82.11 (1997): 3864-3871. 

Bacteria activate sensory neurons that modulate pain and inflammation 

Nociceptor sensory neurons initiate the sensation of pain and defensive behaviors in an organism to protect it from possibly harmful stimuli. Bacteria infections also produce pain--by some unknown molecular mechanisms--which was presumed to be caused by the immune system. In this experiment, the bacteria Staphylococcus aureus was injected into the tissue of mice, and their behavior and sensitivity to mechanical and thermal stimulation was recorded.

It was found that the bacteria directly activated the nociceptors, and the immune response is not necessary for the sensation of pain. Mechanical and thermal hyperglasia was positively coorelated to bacterial load rather than swelling or immune activation; the bacteria activated the neurons by inducing calcium flux via peptides and toxins. 

Chiu, Isaac M., et al. "Bacteria activate sensory neurons that modulate pain and inflammation." Nature 501.7465 (2013): 52-57. 

Transfer of carbohydrate-active enzymes from marine bacteria to Japanese gut microbiota

The gut microbiome supplies humans with energy through carbohydrate active enzymes (CAZymes), which are absent in the human genome. There is an extremley large diversity of CAZymes in the gut microbiome, but how this diversity originated from microbes living outside the gut is an unexplored realm. 

In this experiment, it is shown that the bacteria Zobellia galactanivorans shares the genes coding for porphyranases, agarases and associated proteins (from the marine red algae Porphyra) have been transfered to the gut bacteria Bacteroides plebeius isolated from Japanese individuals. Furthermore, the metagenome analyses conducted show that t porphyranases and agarases are frequent in the Japanese population but absent in the metagenome from North American individuals. Since seaweed heavily contributes to the daily diet in Japan, this indicates seaweeds with CAZyme-producing bacteria may have been how gut bacteria in humans have acquired the CAZymes required, and non-sterile foods may be a factor in CAZyme diversity in human gut microbiomes.

Hehemann, Jan-Hendrik, et al. "Transfer of carbohydrate-active enzymes from marine bacteria to Japanese gut microbiota." Nature 464.7290 (2010): 908-912.

Therapeutic potential of Bifdobacterium breve strain A1 for preventing cognitive impairment in Alzheimer’s disease

Consumption of probiotics may have beneficial effects on the central nervous system and behavior via the gut-brain axis. Therefore, probiotics may be a viable theraputic treatment for managing neurodegenerative disorders.

In this experiment, it was found the oral administration of Bifdobacterium breve strains A1 to AD in Alzheimer’s disease (AD) model mice indicated prevention in cognitive dysfunction. Furthermore, B. breve A1 suppresed the effects of amyloid-β, a protien connected to AD. This suggests the bacteria has potential for theraputic potential to prevent cognitive impairment in AD.

Kobayashi, Yodai, et al. "Therapeutic potential of Bifidobacterium breve strain A1 for preventing cognitive impairment in Alzheimer’s disease." Scientific reports 7.1 (2017): 13510. 

Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve

Is there a direct effect on neurotransmitter receptors in the CNS from bacteria in the gut microbiota? If so, how is this manipulation achieved? In this experiment, the lactic acid bacteria Lactobacillus rhamnosus was found to modify GABA mRNA in the brain, increasing it in cortical regions and reducing it in the hippocampus, amygdala, and locus coeruleus, compared to control-fed mice. 

In one of the experiments, the experimental mice fed L. rhamnosus (JB-1) swam longer than the control fed mice in a water tub with no possible escape. However, this effect dissapeared when the vagus nerve was severed in the experimental group. There was no effect on severing the vagus nerve in control mice. The neurochemical and behavioral effects were absent in vagotomized (removed vagus nerve) mice, showing the vagus nerve as a major communicator between the microbiota in the gut and the brain, forming the aptly named gut-brain axis via the vagus nerve.

Bravo, Javier A., et al. "Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve." Proceedings of the National Academy of Sciences 108.38 (2011): 16050-16055. 

Mechanisms underlying the resistance to diet-inducedobesity in germ-free mice

The gut microbiota is essential for metabolic function and acts as another organ for our human metabolic system. Because of the obesity epidemic, there is increased instrest in how the micriobiome affects energy balence. 

In this experiment, it was found that germ-free (GF) mice are protected against obesity from consuming a Western-style, high sugar, high fat diet. This is associated with their higher levels of AMPK, which is responsible for fatty acid oxidation. However, it was also found that GF mice lacking fasting-induced adipose factor (Fiaf) are not protected from diet-induced obesity, despite having normal AMPK levels compared to wild type. This suggests that GF mice are protected from diet-induced obesity by two complementary but independant mechanisms: elevated levels of Fiaf, and increased AMPK activity. This suggests the microbiome is able to influence both sides to the obesity scale.

What is most interesting is the makeup of the microbiome. When a percentage of Bacteroidetes increase, the Firmicutes decrease by a cooresponding degree, and vice versa. Higher levels of Bacteroidetes have coorelated to lean humans, while higher levels of Firmicutes have been coorelated to obese humans.

Bäckhed, Fredrik, et al. "Mechanisms underlying the resistance to diet-induced obesity in germ-free mice." Proceedings of the National Academy of Sciences 104.3 (2007): 979-984. 

Association between body mass index and Firmicutes/Bacteroidetes ratio in an adult Ukrainian population 

Metagenomic studies have confirmed obesity is associated with a certain microbiota composition. However, there is controversy about this makeup in different human populations. 

In this experiment, the difference between BMI and microbiota composition in fecal samples was recorded from Ukranian population, especially the ratio of Firmicutes/Bacteroidetes. It was found that obese persons in Ukraine have a significantly higher level of Firmicutes and lower level of Bacteroidetes compared to normal-weight and lean adults. This further strengthens that the microbiota balance is essential to metabolic function, and that a higher level of Firmicutes in the human microbiota plays a role in causing obesity.

Koliada, Alexander, et al. "Association between body mass index and Firmicutes/Bacteroidetes ratio in an adult Ukrainian population." BMC microbiology 17.1 (2017): 1-6. 

Human Metabolic Phenotypes Link Directly to Specific Dietary Preferences in Healthy Individuals

Why do some people hate pineapple on pizza, while others don't mind it? Similarly, why do some people like chocolate but others don't? In this experiment, a new "nutrimetabonomic" approach, where behaviors are associated with different metabolic biomarkers, is used to try to determine why humans either prefer or are indifferent to certain foods.

In this study, chocolate "desiring" and chocolate "indifferent" human volunteers were found to have a different metabolic phenotype in relation to their behavioral dietary preference, either "desiring" or "indifferent to" chocolate, which is not affected by ingested food. This could suggest that differences in the microbiome between these two groups is a factor in their dietary preference.

Rezzi, Serge, et al. "Human metabolic phenotypes link directly to specific dietary preferences in healthy individuals." Journal of proteome research 6.11 (2007): 4469-4477. 

Bäckhed, Fredrik, et al. "Mechanisms underlying the resistance to diet-induced obesity in germ-free mice." Proceedings of the National Academy of Sciences 104.3 (2007): 979-984. 

Turnbaugh, P. J., Bäckhed, F., Fulton, L., & Gordon, J. I. (2008). Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell host & microbe, 3(4), 213-223.

Ismail, Nagwa Abdallah, et al. "Frequency of Firmicutes and Bacteroidetes in gut microbiota in obese and normal weight Egyptian children and adults." Archives of Medical Science 7.3 (2011): 501-507. 

Palmas, Vanessa, et al. "Gut microbiota markers associated with obesity and overweight in Italian adults." Scientific reports 11.1 (2021): 5532. 

Kasai, Chika, et al. "Comparison of the gut microbiota composition between obese and non-obese individuals in a Japanese population, as analyzed by terminal restriction fragment length polymorphism and next-generation sequencing." BMC gastroenterology 15 (2015): 1-10. 

Turnbaugh, Peter J., et al. "An obesity-associated gut microbiome with increased capacity for energy harvest." nature 444.7122 (2006): 1027-1031. 

Turnbaugh, Peter J., et al. "A core gut microbiome in obese and lean twins." nature 457.7228 (2009): 480-484. 

Johnson, Jethro S., et al. "Evaluation of 16S rRNA gene sequencing for species and strain-level microbiome analysis." Nature communications 10.1 (2019): 5029. 

Paik, Donggi, et al. "Human gut bacteria produce ΤΗ17-modulating bile acid metabolites." Nature 603.7903 (2022): 907-912.

Zhang, Husen, et al. "Human gut microbiota in obesity and after gastric bypass." Proceedings of the National Academy of Sciences 106.7 (2009): 2365-2370. 

Queipo-Ortuño, María Isabel, et al. "Gut microbiota composition in male rat models under different nutritional status and physical activity and its association with serum leptin and ghrelin levels." PloS one 8.5 (2013): e65465. 

Torres-Fuentes, Cristina, et al. "Short-chain fatty acids and microbiota metabolites attenuate ghrelin receptor signaling." The FASEB Journal 33.12 (2019): 13546-13559. 

Zaibi, Mohamed S., et al. "Roles of GPR41 and GPR43 in leptin secretory responses of murine adipocytes to short chain fatty acids." FEBS letters 584.11 (2010): 2381-2386.