Bugs in the system

Imagine you’ve been in a car accident and your spinal cord is severed. You are paralyzed from the neck down with major nerve damage. The neurologist assessing you begins with a treatment of probiotics, vitamins and nutrients to feed certain bacteria and stimulate your immune system. Over the course of the coming weeks, your stool is continually tested, and your urine and blood sampled, to gauge markers of the types of bacteria thriving in your gut. You receive a transplant of bacteria into your colon from a healthy ‘faecal donor’, and your diet and probiotics are monitored to see how your immune system and microbes are responding, hopefully encouraging them to kick-start your damaged nervous system into self-repair mode.

Sound like quackery? It’s more like a distant, but not impossible, dream of a rapidly growing field of science studying how the bacteria inhabiting our gut are intimately connected
to our brain and central nervous
system (CNS).

Take, for example, a recent study by scientists at the Center for Brain and Spinal Cord Repair at Ohio State University. They demonstrated for the first time that an injury to the spinal cord profoundly alters the kinds of microbes living in the intestines. What’s more, mice fed antibiotics prior to a spinal cord injury have intestines that are overrun with antibiotic-resistant superbugs, and suffer even worse nerve damage and impaired healing. More astonishingly, mice with spinal cord injuries fed probiotics – living ‘friendly bacteria’ – suffered less nerve damage and enjoyed greater motor recovery than the injured mice that didn’t get probiotics.1

Two-way brain chatter

Your gut is around 6–10 metres long from entry to exit, and every square centimetre of it is densely colonized by hundreds of species of bacteria, viruses, fungi and archaea – around 100 trillion of them. While you sleep, these organisms are busy replicating, competing for food, digesting your food, disintegrating your toxins and churning out a host of byproducts – vitamins, antioxidants and anti-inflammatory agents – that ‘talk’ through your immune system and CNS which, in turn, influences the rest of you – your brain, your hormones, your heart and more.

The microbiome – the microscopic cosmos of thousands of species of bacteria, viruses and other microbes that reside in our gut, mouth, skin, nose, among others – is one of the most explosive and revolutionary fields of research.

Scientists have discovered that these bugs, once viewed as agents of disease to be attacked with sterilizers and antibiotics, in fact perform endless vital functions for us. They digest our food, produce our vitamins, compete with pathogens to defend us, churn out metabolites that regulate our immune system and, as the latest research is showing, even command our CNS
and brain.

For decades, alternative practitioners have been pointing to yeast overgrowths – Candida infections and bacterial imbalances – and the ‘leaky gut’ that results from the damage these overgrowths do to the intestinal lining as a major underlying culprit in a wide array of chronic disorders, including mental illness.

And now, thanks to new technology, the emergence of microbiome science is validating their theories. What began a decade or so ago as research confirming a role for microbes in gastrointestinal disease has rapidly expanded to include research into the impact of bugs on the immune system, metabolism and neurological diseases.

The ability of bugs to control behaviour was recently shown experimentally with the jaw-dropping example of a parasite (Toxoplasma gondii) that ‘hijacked’ the brains of rats, manipulating those animals’ sexual and defensive behaviours to favour its own reproduction.2 Indeed, it turns out that our bugs can manipulate our mood and mental health too.

While researchers have long described a ‘gut–brain axis’, there is now growing evidence for a gut–microbiota–immune system–brain pathway that bears constant four-way traffic.

Gut microbiota ‘talk’ to the CNS directly by interacting with immune cells and nerve fibres, and indirectly by secreting metabolites that bypass the blood–brain barrier, say the Ohio State University researchers in their report.1 As 70 to 80 per cent of immune system cells are in the gut – specifically, in gut-associated lymph tissue (GALT) – alongside the microbes, there is an ongoing back-and-forth chatter between the two.

Other, similar studies are just beginning to fill in the details of how this chatter works and to determine the roles that microbes play, beyond what was previously suspected in neurological diseases and even in traumatic injuries. An entirely new field of ‘immunopsychiatry’, focused on this gut–immune system–brain trafficking is now emerging.3

When gut bugs get altered

Many environmental agents have been shown to disrupt the microbiome. Antibiotics designed to kill microbes are the most obvious, but other drugs, such as antacids, can change the gut pH and selectively cull certain species. Heavy metals like mercury and aluminium have also been implicated in microflora disruption,4 as has stress. The foods we eat and the chemicals they contain are also all now suspects – and potential therapies.

The Ohio study specifically demonstrated how spinal cord injury causes populations of bacteria in the gut to change. This ‘dysbiosis’ triggers damage to the gut lining, so allowing ‘bacterial translocation’, the migration of bacteria from within the intestines to areas outside of the gut. The researchers confirmed that the bacteria in their mice had translocated following spinal cord injury from the gut to the blood and liver, kidneys, spleen and lymph node tissues. In contrast, intestinal bacteria were never found in tissues outside of the gut in uninjured mice.

In addition, mice fed antibiotics before the injury suffered ongoing dysbiosis and even worse symptoms and poor recovery. But injured mice given VSL#3 – a medical-grade probiotic powder containing eight species of lactobacilli and bifidobacteria – saw a “protective immune response” that damped down the inflammation triggered and “improved locomotor recovery”.1

This mouse research followed an earlier 2016 study in humans, which also found that spinal cord injury (SCI) disrupted the ecology of gut microbes. “Our results demonstrate for the first time that butyrate-producing [bacteria] are specifically reduced in SCI patients when compared to healthy subjects.”5

This study was another example of the wave of new research implicating changes in the microbiome in brain and neurological disorders. Microbiota profiling, as it has come to be known, has shown a distinct disruption of species balance in disorders ranging from chronic stress and mood changes to autism and obsessive–compulsive dis
order (OCD). What follows are a few other examples of the research linking the gut to the brain.

Stroke injury

A 2016 study found that inducing strokes in mice altered their gut microbiota, activating an immune response that fired signals back to the brain and made the stroke lesions worse.

But when the researchers, from the Ludwig Maximilian University of Munich in Germany, transplanted faecal bacteria from healthy mice into germ-free ones that had suffered strokes, these mice improved more than the controls that had not received bacterial transplants.6

“These findings highlight the key role of microbiota as a potential therapeutic target to protect brain function after injury,” the researchers concluded.6

Multiple sclerosis

Another recent study analyzed the faecal microbiomes of patients with the crippling neurological disease multiple sclerosis (MS) and compared them with the microbiomes of healthy controls, and concluded that MS patients have an underlying gut dysbiosis.

“We observed an increased abundance of Pseudomonas, Mycoplana, Haemophilus, Blautia, and Dorea genera in MS patients, whereas control group showed increased abundance of Parabacteroides, Adlercreutzia and Prevotella genera.”7

Autism

Numerous studies have examined the gut microbiota of children with autism spectrum disorders, and found that the main bacterial phyla (Firmicutes, Bacteroidetes, Fusobacteria and Verrucomicrobia) were significantly altered, with a tendency to be overpopulated with clostridia, Ruminococcus and Akkermansia muciniphila bacteria compared with healthy controls.8

These findings are a partial vindication of the work of Dr Andrew Wakefield, who investigated the gastrointestinal symptoms of autistic children and found live viruses from the measles vaccine in the guts of such children.

Nevertheless, there have been virtually no investigations of whether viruses and other vaccine ingredients can change the gut microbiome. The question remains: do medicines designed to impact the immune system – the middleman in the chatter between gut and brain – have unintended effects on the microbiome?

Anorexia nervosa

One surprising discovery about the microbiome is that it’s related to obesity. This was first discovered when a faecal sample from an overweight teenager was transplanted into her mother to treat a gastrointestinal infection (a now routine procedure for antibiotic-resistant Clostridium difficile infection). This resulted in the mother putting on weight as well. Further investigations have since shown that resident gut microbes do indeed regulate metabolism and play a role in weight gain: transplanting microbes can transplant obesity.

Microbes have now been found to be disrupted in malnutrition as well, and this has raised interest in their role in the most common eating disorder, anorexia, which has traditionally been treated as a psychological disorder. It turns out that anorexics have an overrepresentation in their guts of the predominant gut archaeon Methanobrevibacter smithii, which has a key role in the digestion of carbohydrates and in energy efficiency.9 What’s not known is which came first: the dysbiosis or the anorexia.

Depression and anxiety

Anyone who has ever felt nauseous or lost their appetite because of grief, fear or shock knows that stress has an impact on the gut. It has been more than a decade since animal studies began making the correlation between stress and changes in gut microbes. The connection between stress, depression and anxiety is well established, and dozens of studies are now looking at how these conditions affect bugs in the gut. The big questions – such as which comes first, the microbe shift or the depression – have yet to be answered. Because it’s a two-way street, though, it looks as if correcting the gut microbiome could be a new way to treat depression.10

Obsessive–compulsive disorder (OCD)

Scientists had previously hypothesized that OCD could be the result of antibiotic therapy (including just-in-case doses) causing a “dysfunction of the gut microbiome constituency”, with “stressful life events” being behind this rather poorly understood disorder rather than streptococcal infections. “As the role of microflora to modify key players in the CNS becomes clearer, it is not unreasonable to think that probiotics can play a role in transforming OCD to a more tolerable state,” said author J.C. Rees from the US Centers for Disease Control and Prevention (CDC).11

Migraines

The mouths and intestines of migraine sufferers, it turns out, are populated with greater numbers of bacterial strains that make them more sensitive to certain foods.

Scientists have found that patients with migraines have higher levels of bacteria that process nitrates and nitrites, leading to studies of foods like wine and processed meats, which are high in nitrites and nitrates, as ‘triggers’ for migraine headaches.

Researchers at the University of California San Diego speculate that it may be that the bacteria in the mouth and intestines break down and process these nitrates and nitrites more efficiently than do other bacteria, causing blood vessels in the brain to dilate, so triggering migraines.12 Probiotics in the form of a mouth rinse may be a future treatment based on such research.

Parkinson’s disease

A 2015 Finnish study studied the faecal microbes of 72 Parkinson’s disease (PD) patients and 72 healthy controls, and found that the relative abundance of bacteria of the Enterobacteriaceae family in PD patients was positively associated with the severity of their postural and gait difficulties. The researchers concluded that an intestinal microbiome dysbiosis underlies PD and merits further study.13

Double-edged sword

All this new research means a lot of revising of out-of-date medical textbooks. As the unforeseen roles of bacteria and viruses emerge, doctors need to become more aware of and more cautious about the impact of drugs on the microbial residents of their patients’ guts – and the wide-ranging list of long-term side-effects that can result.

Not only are microbes far more important than previously understood and antibiotics far more dangerous, but even the idea of ‘good’ vs ‘bad’ bugs needs to be thrown out as scientists unravel the complex ecology in the mi
croscopic terrain of the human body. Some bacteria can perform a vital role in controlling overeating and obesity, say, yet in abundance can bring about a loss of appetite and anorexia.

As a component of the immune system, the microbiome also raises questions about how steroid drugs that suppress the immune system can do more harm than good. The 2004 Corticosteroid Randomization After Significant Head Injury (CRASH) trial showed that corticosteroids increased the risk of disability and death for brain-injury patients.14

In one study, Dartmouth Medical School immunologist Lloyd Kasper and his colleagues created a mouse model of MS, then gave the mice broad-spectrum antibiotics orally. The subsequent reduction in gut bacteria protected the animals against developing the disorder.15 In a follow-up study, the team discovered that certain gut microbes might offer even greater protection against neural damage and may have possible applications in MS in humans.16

“You have this balance going on in the gut,” Kasper told The Scientist (1 November 2016). “As long as everything is in balance, it’s homeostatic and everybody’s happy. But something happens in the disease process that that balance is lost.

“If we can drive the immune system from the gut upward and do it in a positive way,” he added, “I think that will give rise to greater benefit and far less side-effects than [current drugs].”

Tending your gut garden

Gastroenterologist Robynne Chutkan advises looking for the following features when choosing a probiotic supplement:

• at least 50 million colony forming units (CFUs), with a predominance of Lactobacillus and Bifidobacterium species and a seal on the bottle certifying that it contains the labelled amounts of bacteria

• at least seven different compatible strains of bacteria

• enteric coating to ensure it’s not destroyed by stomach acid

• good safety record

• good shelf life

• need for refrigeration, which usually means better quality

The best food for microbes

Prebiotics are foods that feed your friendly microbes, so make sure to include the following in your daily diet.

Foods high in ‘resistant starches’, like green bananas and lentils, are fermented by gut bacteria to produce short-chain fatty acids (SCFAs), a primary energy source for cells in the colon that also have anti-inflammatory and anticancer properties

Non-digestible fibres, like those found in beans, bran and flaxseed

Inulin, found in onion, garlic, leek, asparagus and artichoke

Seeds, quinoa and buckwheat, instead of gluten-containing grains

Homemade fermented vegetables, like sauerkraut, kimchi, and fermented drinks like kefir and kombucha, are traditional foods that introduce far more species and numbers of gut bacteria than packaged probiotics.

The main gut culprits

As with any ecosystem, microbiome health is not so much about ‘good’ vs ‘bad’ species as it is about diversity in balance. Here are some microbiome disruptors that have so far been identified.

C-section delivery

If you were delivered by caesarean section rather than vaginally, you may lack many of the microbes you should have acquired on your journey through the birth canal and have, instead, been colonized in infancy by a greater ratio of hospital bugs, such as Staphylococcus species, associated with later onset of asthma, obesity and Crohn’s disease.17

Antibiotics

The average child in the UK receives 10 prescriptions for antibiotics by the time they’re 16 and, in the US, the average child gets 17 antibiotic prescriptions by the time they’re 18 years old.

Antibiotics are like napalm on the microbiome village. A single treatment of clindamycin, for example, can decimate microorganism diversity. It can then take two months for species to begin to recover and up to two years to fully return to pretreatment levels.18

Other studies of a single treatment of ciproflaxicin and clindamycin found they both significantly led to long-term microbiome alterations, diminishing the bug byproduct butyrate, which fights inflammation and cancer, reinforces epithelial defences and regulates gut motility, while inducing lasting changes “the full consequences of which remain unknown”.19

Drugs

Over-the-counter antacids and proton pump inhibitors (PPIs), prescribed for reflux and indigestion, weaken the stomach acids that normally protect against pathogens like C. difficile and yeasts like Candida.20

Corticosteroids, anti-inflammatories like prednisone and chemotherapy agents, used to suppress the immune system, are linked to microbiota shifts and disorders.21

Vaccines can disrupt the body’s microflora in profound and unpredictable ways; scientists call it ‘vaccine-induced pathogen strain replacement’. This is well documented with several types of vaccines, including those against meningococcus, rotavirus and pneumococcus, leaving us vulnerable to overgrowths of pathogens that were once rare and are now possibly more dangerous than the ones we were vaccinated against.22

Stress

A major international report found that stress can change the secretion of mucus and other defence factors that regulate the microbiota in the stomach and gut that, in turn, affects the number and diversity of bugs in the digestive tract.23

Diet

A landmark study by Italian researchers demonstrated the effects of diet by comparing the gut microbes of children in Florence, Italy, with those in rural Burkina Faso.

Both groups had similar microbes in infancy and all had been breastfed. But when they switched to the local diet – the Italian toddlers began eating a high-fat/high-sugar Western diet while the African kids ate a plant-based diet of beans and vegetables – major changes took place in their microbiomes.

The Italian children had fewer species and more bugs associated with obesity, diarrhoea and allergy, while the African kids had a much more diverse collection of bugs, with greater numbers of those associated wit
h fighting inflammation.24

Alcohol

Heavy alcohol intake has long been associated with shifts in bug populations in the small bowel. And now a recent study has shown that even moderate amounts – just one glass of wine a day for women and two for men – can alter the microbiome too.25

Artificial sweeteners

Low- to no-calorie artificial sweeteners have been associated with microbiome changes that can lead to glucose intolerance, a precursor of diabetes.26

How to keep your microbes healthy

The gut–immune system–brain field is still in its infancy. Yet, the emerging consensus is that a healthy gut microbiome – characterized by a wide diversity of species in balance – can protect against disease. “All disease begins in the gut,” Hippocrates is reported to have said.

There is a growing body of research documenting the ability of probiotics, prebiotics (food for bacteria) and certain foods to normalize an out-of-balance microbiome and perhaps also
treat disease.

Even those in psychiatry who usually treat patients with psychotropic drugs are beginning to view probiotics in the same way, referring to them as ‘psychobiotics’.27

The explosion of microbiome research includes numerous studies of the potential of probiotics to treat neurological disorders. But the research is still in its early days, so the choice of probiotic species, and their optimal doses and timings, for each neurological problem and patients have yet to be determined.28

It also appears that microbial health is yet another factor, and conscripting bugs for drugs is not as simple as it sounds – though it may be far less dangerous than using chemicals.

Most studies of the impact of friendly bacteria on diseases of the brain and CNS have looked at only a handful of species of Lactobacillus and Bifidobacterium. Some researchers have used medical-grade commercially available probiotics like VSL#3, which contains multiple (freeze-dried) species of probiotics, with billions of cells per dose, shown to improve gastrointestinal disorders like irritable bowel syndrome (IBS). These products generally require refrigeration to maintain their effectiveness.

As with IBS, though, it may be that manipulating the environment of microbes and controlling the foods they eat – by changing the foods you eat – is a more effective way of creating a diverse microbiome.

In a 2016 review entitled ‘Bread and Other Edible Agents of Mental Disease’, two researchers from the University of Padua in Italy stated that “psychologists and psychiatrists typically fail to appreciate the impact that food can have on their patients’ condition”.

This has prompted them to look at evidence in the scientific literature that the proteins (gluten) in barley, rye and especially wheat make the gut more permeable, encouraging the migration of food molecules to unexpected sites and the release of opioid-like compounds in the brain, so “causing mental derangement”.

As the pair conclude, a “grain-free diet, although difficult to maintain, could improve the mental health of many and be a complete cure for others”.29

Make your own coconut-water kefir

In their book The Body Ecology Diet (Body Ecology, 1994), authors Donna Gates and Linda Schatz offer recipes for fermented foods, including a coconut-water kefir concoction that is tart and fizzy, like a tangy spritzer, not sweet.

1) Gently warm the water drained from three young coconuts (or store-bought coconut water, not milk) to about 32º C (90º F).

2) Pour the warmed water into a sterilized jar and add a starter culture, such as Body Ecology Kefir Starter, which contains Lactobacillus and yeasts.

3) Let the coconut water sit, covered, in a stable warm environment for 36 hours. It’s ready when the water changes to a milky-white colour with slight bubbling or foam on top, a sign that most of the sugar has been fermented by the bacteria and yeasts.