What's bugging you?

Findings from a new study showing that a noninvasive, deep transcranial magnetic stimulation (dTMS) technique helps obese people lose weight, partly by changing the composition of their intestinal bacteria raises the question as to just how much are you under the control of your so-called gut microbiota? The study expands on previous findings that stimulation reduces the cravings for food and induced weight loss in obese individuals. Unlike deep brain stimulation, dTMS does not need an operation or implantation of electrodes. Instead, an electromagnetic coil is placed on the scalp and sends magnetic pulses to stimulate specific deep regions of the brain. Currently approved in the US for treating major depression, dTMS is being studied in some countries for the treatment of other neuropsychiatric disorders, especially addiction.

For years we have studied the interaction between our brain and gut, learning that its complexities run deeper than we initially thought. It is clear that our minds are, in some part, controlled by the bacteria in our bowels. But what sort of impact does it have? We know that the gut defends itself (and us) against pathogens, but, at the same time, it encourages the survival and growth of 'healthy' gut bacteria. More than a trillion of these single-celled organisms live in each gram of intestinal content, with a best guess of 40 trillion gut bacteria calling you 'home' - at least 10 trillion more than the 30 trillion cells that make up your own body. In a very real sense, we are more bacteria than man. Although there are up to 1,000 different species, most of our gut bacteria belong to the 30 or 40 groups that we collectively call the microbiome. For the cost of free rent, food and central heating, the microbiome breaks down dietary fiber down into short-chain fatty acids that we can then absorb and use, metabolises several compounds on our behalf and plays a role in the synthesis of vitamins B and K.

So, you can imagine that the happy balance between landlord and occupier is beneficial for both parties - but what happens when this balance breaks down? We are all well versed in the somewhat catastrophic and acute challenges we face following breakdown of balance within the gastrointestinal environment but recent research implies that there are more subtle forms of chronic dysregulation that can have less obvious and yet more concerning effects on our health.

Linking gut and brain

It is essential for the brain to be aware of what is happening in the guy: availability of food and food processing issues affect nutrition absorption and if our gut is facing a pathogen attack the brain needs to be informed. The organs communicate via hormonal, immunological, and neurological pathways (the central and enteric nervous systems) that have been termed the gut-brain axis. We have all experienced the link in action - for example bowel symptoms when we feel stress or anxiety. The connection has long been documented in the scientific literature - who can forget Pavlov's dogs? More recently, however, a new level of cooperation between our microbiome and the gut-brain axis has emerged. With the understanding that most biological communication pathways are bidirectional in nature the question has arise as to whether the bacteria in our gut affect our psychology and behavior. Only now are we beginning to suspect the impact of the brain-gut-enteric microbiota axis.

Stress and the gut

The hypothalamic-pituitary-adrenal (HPA) axis is believed to be your primary responder to stress, a major player in limbic responses it is heavily involved in emotions and memory. When activated by stress the HPA axis moderates release of cortisol - the "stress hormone" - which has a variety of effects on many organs, including the brain and gut. Thus our psychological states impacts directly on the cells of the gut, including epithelial and immune cells, enteric neurons, interstitial cells of Cajal (the pacemakers of the bowels), and entero-chromaffin cells (seretonin synthesizing cells). These cells are also influenced by the microbiota - but can the microbiota influence the brain and thus your psyche in some sort of two-way dialogue?

Twenty years ago it was observed how the health of patients with hepatic encephalopathy - a decline in brain function due to severe liver disease - improved following oral antibiotics. Later studies provided further hints that the microbiome had more than a passing influence on states of mind such as anxiety and depression. There have even been links proposed between imbalance in the microbiota and autism - with research implying that children with autism often have abnormal and less diverse communities of bacteria in their gut. It may be that gut microbes can alter levels of neurotransmitter-related metabolites, affecting gut-to-brain communication and/or altering brain function. Mice with no gut bacteria certainly have exaggerated responses to stress and altered memory function - something is clearly going on but it impossible to extrapolate into humans. Other approaches have investigated the effects of the neuroactive compounds that gut flora produce or differences in the gut flora of individuals with psychiatric or neurological differences. The work currently remains inconclusive.

Components of the gut flora-brain axis

The way that gut bacteria can affect over human psychology seems to be coming slowly into focus. Stress increases the permeability of the intestinal lining exposing both the immune system and the neuronal cells of the enteric nervous system to the bacteria. This could be one way that bacteria influence us. There may also be more direct routes, for example through direct contact of the microbiome with the sensory neurons of the enteric nervous system. In addition, food-borne pathogens can access stress circuits directly by activating the vagus nerve. Studies have shown how sensory neurons are less active in germ-free mice, and neuron activity levels return to normal when they are given probiotics to restock their microbiome. When data from human and animal studies are combined it is clear that dietary supplementation with probiotic cultures of Bifidobacterium and Lactobacillus over a 2-4-week period that tere are improvements in psychiatric disorder-related behaviors including anxiety, depression, autism spectrum disorder, obsessive-compulsive disorder, and memory abilities, including spatial and non-spatial memory. In another study, researchers showed how age-related decline in memory could be reversed in rats by altering the levels of Actinobacteria and Bacterioidetes in their gut with probiotics.

Conclusions

There has been some concern over the credibility of the microbiome-gut-brain axis proposition and judgment over the quality of the research conducted as well as those conducting the research. Although the available data points to some form of relationship, the failure to establish reproducible evidence that can describe the observations continues to plague research. No doubt the multifactorial nature of the different variables will serve to confound efforts to discover the underlying mechanisms. Eventually we will develop an understanding of the microbiome that allows it to serve as an early warning system or diagnostic tool for certain conditions and medicines specifically targeting the microbiome. Perhaps appreciating that despite our intelligent and scientific achievements we remain (partially) under the control of single-celled organisms.