The microbiome-gut-brain axis: from bowel to behavior
Behavioral and neurochemical consequences of growing up germ-free
Neufeld and colleagues in this issue of this Journal11 use female germ-free mice to demonstrate that the absence of a conventional microbiota results in a reduction in anxiety behavior in the elevated plus maze, a well validated model of anxiolytic action (see Fig. 1). These authors also show an upregulation in the expression of brain derived neurotrophic factor (BDNF) mRNA in the dentate gyrus of the hippocampus of these germ-free animals. Brain derived neurotrophic factor is crucial for supporting neuronal survival and encouraging the growth and differentiation of new neurons and synapses and thus is involved in the regulation of multiple aspects of cognitive and emotional behaviors.12 Whilst there is a clear relationship between chronic stress states, major depression and BDNF,13 the association between anxiety and BDNF appears to be more complex with the authors finding positive, negative and no correlation between hippocampal levels and anxiety.14–16 Thus, it is unclear whether the changes in hippocampal BDNF observed in the study of Neufeld and colleagues actually relates to the behavioral changes observed.
Interestingly, and somewhat discordant with the behavioral data, an increase in the stress hormone corticosterone was noted in the plasma of the germ-free mice. Moreover, a decrease in the NR2B subunit of the NMDA receptor in the amygdala, but not hippocampus, of germ-free animals was observed which the authors speculate may contribute to the anxiolytic-like effect noted. In addition, a down-regulation of the 5-HT1A auto receptor was also present in the dentate gyrus of the germ-free mice.11
These data together provide important and direct evidence that microbiota can influence brain and behavior, in this case anxiety. They build on previous studies from Sudo and colleagues17 which demonstrate that male germ-free mice have an increased stress response (although no basal changes in hypothalamic pituitary adrenal axis function were noted in these studies) coupled with decreased hippocampal and cortical BDNF, and decreased NR1 (hippocampus) and NR2A (hippocampus and cortex).17 The reasons for the discrepancies between the molecular changes in these studies and that of Neufeld and colleagues are unclear at present. Gender may play a role in such effects. Indeed, recent data from our laboratory show that the neurochemical and endocrine but not immune effects of growing up in a germ-free environment is only evident in male animals.18 Another important difference between the studies is the method of mRNA expression analysis (in situ hybridization vs quantitative real-time PCR). One significant caveat to the data generated by Neufeld and colleagues is that their studies were carried out on commercially sourced germ-free animals and were conducted just 48 h following arrival at their facility. The impact of transport stress and the lack of information regarding gnotobiotic status are two major confounds to the study.19 Moreover, whereas Sudo and colleagues demonstrated that recolonization with Bifidobacteria species reversed the germ-free induced effects, no attempt at recolonization occurred in Neufeld et al.’s study. However, despite these limitations their work is among the first to show a direct link between anxiety-related behavior and the microbiota and thus is an exciting and important contribution to the literature.
Probiotics and behavior/central neurotransmitters
Probiotics are beneficial in the treatment of the gastrointestinal symptoms of disorders such as IBS.20 Clinical evidence is mounting to support the role of probiotic intervention in reducing the anxiety and stress response as well as improving mood in IBS patients and those with chronic fatigue.21–23 Recently, a study assessing the effect of a combination of Lactobacillus helveticus and Bifidobacterium longum on both human subjects and rats showed that these probiotics reduced anxiety in animals and had beneficial psychological effects with a decrease in serum cortisol in patients.24 While the mechanism of action is not known, some probiotics do have the potential to lower inflammatory cytokines,20,25 decrease oxidative stress and improve nutritional status.21 The modulation of systemic inflammatory cytokines and oxidative stress could potentially lead to increased BDNF,21 known to be involved in depression and anxiety.13,14
Lactobacillus reuteri, a potential probiotic known to modulate the immune system26 decreases anxiety as measured on the elevated plus maze as well as reducing the stress-induced increase of corticosterone in mice.27 This probiotic alters the mRNA expression of both GABAAand GABAB receptors in the central nervous system. Alterations in these receptors are associated with anxious and depressive-like behaviors in animal models. Vagotomy in these animals prevented the anxiolytic and antidepressant effects of this bacterium as well as the effects on the central GABA receptors. This suggests that parasympathetic innervation is necessary for L. reuteri to participate in the microbiota-brain interaction.
Previous studies28 have shown that probiotic agents can modulate antidepressant-like behavior with Bifidobacterium infantis having antidepressant properties in the forced swim test, a well-established model in the evaluation of pharmacological antidepressant activity.29Chronic B. infantis administration also led to a suppression in stimulation-induced increases in peripheral pro-inflammatory cytokines and increases in plasma tryptophan,28 both of which have been implicated in depression.30,31 We have also investigated the impact of B. infantis on a preclinical model of IBS (maternal separation model)32 and showed that this bacterium was able to reverse some of the early-life stress-induced changes.
Taken together, it is clear that certain probiotic strains can modulate various aspects of the microbiome-gut-brain axis.33 However, these effects are bacterial strain dependent and care must be taken in extrapolating data obtained from one organism to another. Nonetheless, the accumulating data suggest a clear ability of probiotic and potential probiotic strains to modulate brain and behavior.
There is more at the link maybe this should have its own thread but seems related to me.. other might miss it by itself. I was interested in L.Reuteri specifically as I have been researching probiotics for a couple of wks now. While doing this research I have learned that Bifidobacterium infantis is the one a lot people with bowel issues find helpful. While I was looking to find a probiotic to help with bowel issues I found the L. Reuteri probiotic hit a lot more of my symptoms. Including tooth issues as it apparently has the ability to kill bacteria in the gut ...heal the gut lining and is involved in immune modulation.
independently of the brain. The enteric nervous system of the gut is comprised of about 500 million neurons. The enteric nervous system can “think”, “remember” and “learn” on its own accord.
The enteric nervous system lines the mucosa of various organs: esophagus, stomach, small intestine, large intestine, pancreas, gall bladder, and biliary tree.
The ENS is involved in the regulation of several essential digestive functions. Most notably:
- Peristalsis, intestinal motility: bowel muscular contractions
- Digestive enzyme secretion: to break down food particles
- Participates in the regulation of esophageal muscles: moving food to your stomach
- Motility of the gall bladder, releasing bile into the duodenum
- Assists the hormone secretin in releasing pancreatic enzymes
- Exchange of fluids and electrolytes in the gut
- Blood flow through the gastric mucosa
- Also involved in the regulation of the gastic and esophageal sphincters: preventing acid food from entering the throat, and allowing food to pass into the duodenum from the stomach
- Uses more than 30 neurotransmitters, including serotonin, GABA, dopamine, acetylcholine
Many researchers postulate that the enteric neurons have an important role to play in regulating behavior. This is likely due to the fact that the enteric nervous system communicates with the brain via the vagus nerve. It is known that strains of intestinal bacteria have a powerful regulatory effect on the enteric neurons. It is also known that these same bacterial colonies can induce behavior-modifying effects.
“As Bifidobacterium longum decreases excitability of enteric neurons, it may signal to the central nervous system by activating vagal pathways at the level of the enteric nervous system.”
Lactobacillus reuteri has been studied for its anti-anxiety effects and for its powerful modulation of the immune system, especially the inhibition of TNF-a. Additionally, L-reuteri is well established to modify the activity of the neurotransmitter GABA in the central nervous system. The same is true for lactobacillus rhamnosous.
L.Reuteri came out as the star for me personally it is found in breast milk and each species it is a bit different so has to come from human breast milk. I am still a firm believer in trying only one thing at a time and now sourcing this BioGaia seems to be the only game in town. So if I can find it I will be trying it and reporting back.
Chemical and trauma-induced injury
Treating colonic tissue from rats with acetic acid causes an injury similar to the human condition ulcerative colitis. Treating the injured tissue with L. reuteri immediately after removing the acid almost completely reverses any ill effects, leading to the possibility that L. reuteri may be beneficial in the treatment of human colitis patients."
I was told I have antibiotic induced colitis so this is the one I am going to try first. I will let you know what happens.
This may need to be moved if so please put a link to where it goes to my page....thanks.
WARNING THIS WILL BE LONG
Had a car accident in 85
Codeine was the pain med when I was release from hosp continuous use till 89
Given PROZAC by a specialist to help with nerve pain in my leg 89-90 not sure which year
Was not told a thing about it being a psych med thought it was a pain killer no info about psych side effects I went nuts had hallucinations. As I had a head injury and was diagnosed with a concussion in 85 I was sent to a head injury clinic in 1990 five years after the accident. I don't think they knew I had been on prozac I did not think it a big deal and never did finish the bottle of pills. I had tests of course lots of them. Was put into a pain clinic and given amitriptyline which stopped the withdrawal but had many side effects. But I could sleep something I had not done in a very long time the pain lessened. My mother got cancer in 94 they switched my meds to Zoloft to help deal with this pressure as I was her main care giver she died in 96. I stopped zoloft in 96 had withdrawal was put on paxil went nutty quit it ct put on resperidol quit it ct had withdrawal was put on Effexor... 2years later celexa was added 20mg then increased to 40mg huge personality change went wild. Did too fast taper off Celexa 05 as I felt unwell for a long time prior... quit Effexor 150mg ct 07 found ****** 8 months into withdrawal learned some things was banned from there in 08 have kept learning since. there is really not enough room here to put my history but I have a lot of opinions about a lot of things especially any of the drugs mentioned above.
One thing I would like to add here is this tidbit ALL OPIATES INCREASE SEROTONIN it is not a huge jump to being in chronic pain to being put on an ssri/snri and opiates will affect your antidepressants and your thinking.
As I do not update much I will put my quit date Nov. 17 2007 I quit Effexor cold turkey.
There is a crack in everything ..That's how the light gets in