Tag Archives: BDNF

New book cover, and ebook price is cut to $6.99!

Hi Rez Cover ebook gut brain

I’ve been working on rewriting my book description, as I’ve never liked the one I used. So, today’s post is all about updates on TSF. I’m working on the next book too, and it’s all about applying the information from TSF to everyday life! So, here’s the update so far, with a linky at the bottom:

What if many of the things you thought you knew about being human did not actually work the way you were taught?

What if scientific research into gut bacteria had revealed huge amounts of information about their role in human function, health, emotions and appetite and healthcare hadn’t caught up at all?

What if you could find out the key to controlling your weight without starving yourself or undergoing dangerous surgery?

What if the book you’re looking at could teach you about the explosion of scientific research on the microbiome, without you having to read a few thousand studies to understand it?

You’ve probably heard that our gut bacteria vastly outnumber our human cells, and our gut bacteria’s gene pool includes more than one hundred times the gene count as our human cells. What does that mean and how does it work?

If you’re interested in knowing more about “what makes us tick” physically and emotionally, how to hurt less and age more gracefully, then this book is for you!

If you’re tired of books that state the author’s opinion or make broad claims without scientific backing or support, this book includes about 1300 peer-reviewed research studies, and the e-book has links to those studies on the National Library of Health/National Library of Medicine.

One of the inspirations for this book was research published by the late Prof. Eshel Ben-Jacob, a brilliant Israeli researcher. I was able to share this book with him before he passed away, and this is what he said about it:

“This excellent and long needed book presents in a clear and sound manner the recent dramatic findings about our gut bacteria. These thousands of trillions microorganisms living inside us play a crucial role in regulating our well-being throughout life. The new message is of great importance to the entire medical community, life sciences researchers, as well as the general public. Realizing the role of gut bacteria can help each of us to better understand the effect of nutrients, as mediated by the gut bacteria, on our body in health, in disease and in special times, such as pregnancy, nursing or periods of high stress. For example, we now understand that the massive use of antibiotics in children, adults and agriculture has endangered our vital microbiome and is liable to cause diseases such as Type 2 diabetes on a global scale. The gut microbiome is emerging as a vital part of humanity, without which health and happiness are severely compromised. The time has come for this knowledge to be widely understood!”

Professor Eshel Ben-Jacob, International member of the American Philosophical Society

Professor of Physics
The Maguy-Glass Professor
in Physics of Complex Systems
School of Physics and Astronomy
Tel Aviv University, 69978 Tel Aviv, Israel

http://www.amazon.com/Symbiont-Factor-Bacteria-Microbiome-Redefines-ebook/dp/B00LV6H1UY/ref=tmm_kin_swatch_0?_encoding=UTF8&qid=1443640302&sr=8-6

Australopithecus sediba, our vegetarian past? What does it take to grow a brain?

Very detailed and scientifically correct human skullcutaway, with all brain details, mid-sagittal side view, on white background. Anatomy image.

I’m watching a PBS special about some new fossils of our ancestors, specifically Australopithecus sediba, discovered in a cave in South Africa. I noted that the reconstruction of the ribcage appeared to be wide and consistent with an individual having a large abdomen, similar to a gorilla, providing room for a long enough digestive tract to digest a mostly vegetable diet. Just as horses and cattle need a relatively large abdomen to provide a “fermentation vessel”, so too the gorilla (and A. sediba) have a skeletal structure to accommodate this structure. Later in the show, it was revealed that dental calculi (plaque) provided evidence of a vegetarian high-fiber diet. This validates my observation of the ribcage dimension and clinches, in my mind, that this ancestor was a veggie eater. The braincase suggests that this ancestor had not yet evolved the larger brain, particularly frontal lobes, characteristic of modern humans.

Scientists have identified two requirements for the evolution of large brains (termed “encephalizaton”). The first requirement is sociality, as much of the brain enlargement is frontal lobe and this part of the brain is where much of our social dynamic originates from. Executive functions, self control, altruism are frontal lobe functions for the most part. Species with large frontal lobes have advanced social societies (dolphins, whales, elephants are prime examples). The second requirement is DHA, an essential fatty acid found mostly in seafood but also in fats of prey animals.

It is thought by many research authors (see Ben-Dor and Jandhayala below in references) that mankind’s encephalization involved a shortening of the digestive tract to support eating more energy-dense foods like meats and fats. The consumption of plant material for a diet requires that most of the waking time be spent foraging and eating, and the digestive process depends on a large gut. The development of tools and weapons was a necessary step to becoming an omnivore, as was the development of social structure necessary to successfully hunt larger prey animals.

It is for these reasons that a diverse and unique gut bacteria were a critical component of our development. The gut bacteria help produce BDNF (brain derived neurotrophic factor), required for the development of new brain cells and is essential for plasticity and learning. High levels of DHA in the diet also help with BDNF production. The human brain requires essential fats in the diet to support both its energy requirements and its health. There is evidence that during the phases where early man was developing the large brain characteristic of our species, diet shifted from plant based to include meat and fat. Those near the ocean likely obtained all the DHA fats needed from seafood, while those dwelling inland may have obtained it from…brains and marrow fat. Fossil remains show that prey animals consumed by early man have been found with cranial vault damage suggesting that the brain was removed for consumption. Obviously, those living near the ocean had a much easier time of things, as clams do not run fast nor pose much of a threat! Ancient settlements near water are often characterized by large piles of seashells.

What this boils down to is that we developed our big and (usually) useful brains due to a dietary shift away from vegetarian to eating meat and animal fats. Accompanying this shift, and codependent on it, was a behavioral shift toward toolmaking, weapon use, and increased social interaction. It should also be noted that as I explained in The Symbiont Factor, a higher functioning brain is codependent on a diverse microbiome. More brain activity helps the gut become healthy and encourages a healthy microbiome, and vice versa. The modern Western diet has high levels of omega-6 fats, which displace DHA and increase inflammation, leading to more disease and less brain development! That type of diet is also typically very unheathy for the microbiome, further hindering brain function. A vegetarian or vegan diet can still be brain-healthy, but apparently not without additional supplementation of DHA as even the presence of healthy fats in vegetable sources does not provide enough DHA due to a low conversion rate. That subject is discussed at length in some of the references provided, and may be fodder for many who have strong opinions one way or the other.

References:

The Symbiont Factor: http://tinyurl.com/ppyh9yr

Energetic and nutritional constraints on infant brain development: implications for brain expansion during human evolution:http://www.ncbi.nlm.nih.gov/pubmed/24928072

Docosahexaenoic acid, the aquatic diet, and hominin encephalization: difficulties in establishing evolutionary links. http://www.ncbi.nlm.nih.gov/pubmed/17160979

Encephalization is not a universal macroevolutionary phenomenon in mammals but is associated with sociality. http://www.ncbi.nlm.nih.gov/pubmed/21098277

Evidence for the unique function of docosahexaenoic acid during the evolution of
the modern hominid brain. http://www.ncbi.nlm.nih.gov/pubmed/10419087

Man the Fat Hunter: The Demise of Homo erectus and the Emergence of a New Hominin Lineage in the Middle Pleistocene (ca.400 kyr) Levant http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235142/

New Insights into the Evolution of the Human Diet from Faecal Biomarker Analysis in Wild Chimpanzee and Gorilla Faeces http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4465628/

Docosahexaenoic Acid (DHA): An Ancient Nutrient for the Modern Human Brain http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257695/

Role of the normal gut microbiota: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4528021/

https://en.wikipedia.org/wiki/Australopithecus_sediba

http://www.pbs.org/wgbh/nova/next/ancient/new-ancient-hominid-skeleton-found-in-south-africa/

 

ADHD and the Microbiome: Any useful connections?

ADHD

Life sometimes keeps us quite busy, doesn’t it? I apologize to you, my readers, for the scarce blog posts. I’ve been in the process of pulling off an epic home move of about 1700 miles! So, I write this post while in a campground in Lamoine, Maine USA where I’ve been hunting up a new home for my family and I.

I did quite a bit of research reading about ADHD recently, and thought I would share a few thoughts about it.  Most of these thoughts are summarized in the flow chart drawing I created; refer to it when reading this blog post and you’ll see what I mean. What can be learned from a simple uBiome stool sample that can help with ADHD? Well, it turns out that there is quite a bit to look at there! As usual, this isn’t meant to replace your physician’s advice, and it is an example-which may not exactly describe your situation. You should consider using uBiome to run your (or your child’s) sample to see what your particular situation consists of.

The first thing to consider is the imbalance that frequently occurs in a microbiome. You see, it isn’t just about how many species of bacteria live in your gut, it is also about the relative numbers of those species. uBiome, after processing your sample, shows this in the simplest way by clicking on Taxonomy tree. In this format, the larger circles indicate larger populations while the smaller ones indicate, well, smaller. Clicking on each allows one to expand the data down from the phylum level all the way down to the genus level (remember, all life is cataloged by Kingdom, Phylum, Class, Order, Family, Genus, Species. We usually use Genus, Species to identify organisms, such as Homo sapiens or Helicobacter pylori.) When expanding these circles, often there is an obvious imbalance. At this point, I’m going to share some very specific information, and some or all of it may not apply to you or your child. It is an example of how a uBiome analysis can correlate with a condition and symptoms, directing some interventions. One recent patient case was a good example; the only large circles were Firmicutes, which is not such a bad thing. Opening that led to Clostridia being dominant, while Bacilli was minimal. This is meaningful because Bacilli includes Lactobacillus-one of the definite “good guys” that keep things working well. The phylum Actinobacteria was also minimal, significant because it includes another desirable genus, Bifidobacterium. This organism is an initial colonizer of the gut, tames the immune system, and also works with Lactobacillus to produce BDNF.

BDNF stands for Brain Derived Neurotrophic Factor, and it is necessary for the brain to develop new connections and grow/adapt to the life an individual leads. It is needed for plasticity, that ability of the brain to learn and adapt as needed. Low levels of BDNF are associated with ADHD. Your microbiome helps your brain to produce BDNF. Remember that a big part of what your brain learns to do as you grow up is actually blocking things out, not paying attention to more of them. It is a learning process, and in order to concentrate to accomplish tasks we must learn to attenuate non-essential information. This is also necessary for the brain to conserve fuel, because having a neural response to every incoming signal would burn a lot of fuel-in fact, enough to run out in some areas and cause Oxidative Stress.

Oxidative stress can result from depressed levels of antioxidant reserves or from too much stimulation. When nerve cells get overstimulated, they build up waste products and the energy-producing mitochondria become damaged. This is a “cellular death spiral”, because as soon as the mitochondria become damaged, the cell’s capability to metabolize fuel and produce energy is compromised, leading to more oxidative stress and further damage. This has been identified as part of the disease process in Alzheimer’s and Parkinson’s as well as ADHD and Autism. One of the problems that can promote Oxidative Stress is Inflammation.

Inflammation occurs when the immune system become too reactive and begins to attack tissue that is “self” and not “intruder/enemy”. Bifidobacteria are known for helping to dampen the immune inflammatory response, and a deficiency of Bifido contributes to inflammation. Again, inflammation is a key building block of…yes, all the same neurologic diseases. Low levels of Bifidobacteria and Lactobacillus are also significant because these organisms produce a neurotransmitter called Gamma Amino Butyric Acid or GABA.

GABA is an inhibitory neurotransmitter in the brain, and calming drugs or herbs often boost GABA levels. Valerian root or Valium (copycat drug companies, you know?) are good examples as is Kava Kava. Low levels of Lacto and Bifido gut bacteria result in low levels of GABA at the brain. Low levels of GABA at the brain result in less inhibition…ergo, more stimulation! And, the process continues in a positive feedback loop.

It is interesting to note that one intervention that helps elevate GABA and BDNF is exercise. Kids with ADHD are known for often being hyperkinetic, so if you wondered why, it is their brain’s way of balancing the equation to save nerve cells! When kids are reprimanded by teachers and parents are shamed into medicating their children’s “high energy”, it can be detrimental to the developmental process for this reason. This doesn’t mean that doing nothing is better, as a child must be able to focus in order to be able to learn. It just means that medicating their energy level down does not address the root causes of the problem.

So, what would be some natural interventions? First, improved nutrition. Any food that is causing more inflammation needs to be removed from the diet. Often that is sweets (note that Clostridia like sweets) and sometimes specific items such as gluten containing foods. Adding probiotics that contain the Lacto and Bifido organisms (in this patient example) can of course be helpful, but more so if they are also fed the prebiotic fibers that they need to survive (again, ideally this is case-specific). Both can be added to a fruit and vegetable smoothie that is tasty. Neuroprotective supplements such as N-Acetylcysteine will help to minimize the neuronal damage that is occurring. Also DHA/Omega-3 oils are neuroprotective and have been shown to help with ADHD. Curcumin can also reduce the neuroinflammation and is protective as well. It can also help settle gut function and heal the membranes of the intestines if they were inflamed too. Eating less processed food and more fresh (organic as possible) fruits and vegetables helps.

All of these steps are best carried out after having a stool sample analyzed for gut bacteria. Only after seeing the “bacterial census” is it possible to be extremely specific. A different patient’s samples could result in different recommendations! Please contact me for more details should you wish to find out more or schedule an analysis. This does not have to be done locally, as I only need the data from uBiome and a patient questionnaire to determine recommendations. Some of the supplements recommended are not case-specific, such as NAC, DHA/Omega and Curcumin as these will help most types of situations as will a healthier diet. The probiotic formulation is ideally case-specific, as is the prebiotic fibers and these will preferentially feed some categories of organisms more than others.

With proper lab work and specific interventions, it is possible for many individuals with ADHD to control and manage their situation more effectively. For some, it will be more of a cure, with no medication needed. For others, it may mean less medication is needed or the medication works more effectively. It is important to realize that we are all different, and our situations are also different!

Sources for supplements: http://progressivelabs.com/   You’ll have to register to order from them, and it requires specifying who referred you. Please feel free to put my name on that line, and then you will be able to receive your supplements directly from the same manufacturer I use!

References:

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TNF-alpha inhibition prevents cognitive decline and maintains hippocampal BDNF levels in the unpredictable chronic mild stress rat model of depression.

Şahin TD, Karson A, Balcı F, Yazır Y, Bayramgürler D, Utkan T.

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Effect of dietary supplementation of Bacillus subtilis B10 on biochemical and molecular parameters in the serum and liver of high-fat diet-induced obese mice.

Lei K, Li YL, Wang Y, Wen J, Wu HZ, Yu DY, Li WF.

J Zhejiang Univ Sci B. 2015 Jun;16(6):487-95. doi: 10.1631/jzus.B1400342.

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Enteric short-chain fatty acids: microbial messengers of metabolism, mitochondria, and mind: implications in autism spectrum disorders.

MacFabe DF.

Microb Ecol Health Dis. 2015 May 29;26:28177. doi: 10.3402/mehd.v26.28177. eCollection 2015.

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26031685

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Clinical trials of N-acetylcysteine in psychiatry and neurology: A systematic review.

Deepmala, Slattery J, Kumar N, Delhey L, Berk M, Dean O, Spielholz C, Frye R.

Neurosci Biobehav Rev. 2015 Aug;55:294-321. doi: 10.1016/j.neubiorev.2015.04.015. Epub 2015 May 6. Review.

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Gastrointestinal dysfunction in autism spectrum disorder: the role of the mitochondria and the enteric microbiome.

Frye RE, Rose S, Slattery J, MacFabe DF.

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Comparing interval and continuous exercise training regimens on neurotrophic factors in rat brain.

Afzalpour ME, Chadorneshin HT, Foadoddini M, Eivari HA.

Physiol Behav. 2015 Aug 1;147:78-83. doi: 10.1016/j.physbeh.2015.04.012. Epub 2015 Apr 11.

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Probiotics as potential antioxidants: a systematic review.

Mishra V, Shah C, Mokashe N, Chavan R, Yadav H, Prajapati J.

J Agric Food Chem. 2015 Apr 15;63(14):3615-26. doi: 10.1021/jf506326t. Epub 2015 Apr 6.

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A possible link between early probiotic intervention and the risk of neuropsychiatric disorders later in childhood: a randomized trial.

Pärtty A, Kalliomäki M, Wacklin P, Salminen S, Isolauri E.

Pediatr Res. 2015 Jun;77(6):823-8. doi: 10.1038/pr.2015.51. Epub 2015 Mar 11.

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Increased levels of plasma glial-derived neurotrophic factor in children with attention deficit hyperactivity disorder.

Shim SH, Hwangbo Y, Yoon HJ, Kwon YJ, Lee HY, Hwang JA, Kim YK.

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Evaluation of improved γ-aminobutyric acid production in yogurt using Lactobacillus plantarum NDC75017.

Shan Y, Man CX, Han X, Li L, Guo Y, Deng Y, Li T, Zhang LW, Jiang YJ.

J Dairy Sci. 2015 Apr;98(4):2138-49. doi: 10.3168/jds.2014-8698. Epub 2015 Jan 23.

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The role of the brain-derived neurotrophic factor genotype and parenting in early life in predicting externalizing and internalizing symptoms in children with attention-deficit hyperactivity disorder.

Park S, Kim BN, Kim JW, Jung YK, Lee J, Shin MS, Yoo HJ, Cho SC.

Behav Brain Funct. 2014 Nov 25;10:43. doi: 10.1186/1744-9081-10-43.

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Gut microbes and the brain: paradigm shift in neuroscience.

Mayer EA, Knight R, Mazmanian SK, Cryan JF, Tillisch K.

J Neurosci. 2014 Nov 12;34(46):15490-6. doi: 10.1523/JNEUROSCI.3299-14.2014. Review.

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The Physiology of BDNF and Its Relationship with ADHD.

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Excitatory GABA induces BDNF transcription via CRTC1 and phosphorylated CREB-related pathways in immature cortical cells.

Fukuchi M, Kirikoshi Y, Mori A, Eda R, Ihara D, Takasaki I, Tabuchi A, Tsuda M.

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Prebiotic feeding elevates central brain derived neurotrophic factor, N-methyl-D-aspartate receptor subunits and D-serine.

Savignac HM, Corona G, Mills H, Chen L, Spencer JP, Tzortzis G, Burnet PW.

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Babies, Breasts, Brains and Bugs: How the Microbiome Helps Build a Baby’s Brain-and How Autism Can Happen if it Doesn’t!

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The human microbiome has been the focus of intense scientific scrutiny for the last decade and some truly surprising discoveries have been made. One of the most interesting is the finding that the gut bacteria communicate with the brain through the Vagus nerve. The brain and the gut bacteria have constant cross-talk through what is known as the microbiome-gut-brain axis. The vagus nerve is the parasympathetic output of the brain and serves to provide motor function to the digestive tract. Reduction of output of the vagus nerve results in sluggish intestinal activity. In the newborn, this sluggishness can result in constipation and colic as well as inflammation. There are many factors necessary for the proper development of baby’s brain, some of which we will focus on here:

-Vagal tone is necessary for the brain to develop normally. Reduced vagal tone is one of the best indicators of neurologic health of a newborn and poor vagal tone is associated with social, behavior, emotion and communication problems later in life. It is also associated with failure to grow and gain weight. Autism is an example of these problems! Probiotic bacteria such as Lactobacillus rhamnosus stimulate vagal function, resulting in improved weight gain and brain function. Other factors that have been found to improve vagal tone include Kangaroo Care (so named in the care of premature infants, it used to be called a mother holding her baby skin-to-skin and cuddling). Massage therapy of the newborn improves vagal tone as well. One of the most interesting factors that improves vagal tone is when a mother plays with an infant, making faces and communicating. This interaction has been found to greatly increase vagal tone and improve digestion, growth, and brain functions related to communication, expression and social behaviors. Of course, not doing this has the opposite effect! If the mother is depressed or angry and has a flat expression the baby’s brain does not develop as well. This may be one of the undiscussed causes for the increased incidence of autism-as autistic individuals become old enough to be parents, they are uniquely not suited to this face-to-face play and expression, thereby hindering their child’s brain development in a manner similar to their own. The increasing use of day care centers and babysitters has this effect as well, as babies do not generally receive the same level of interaction a they would with a full-time mother.

-Brain Derived Neurotrophic Factor or BDNF: this vital neurotropin helps the brain to grow new neurons and new synapses and is essential for learning to occur. Without normal levels of BDNF, a baby could not learn new behaviors and develop normally. Abnormally elevated levels of BDNF have been found to occur in autistic individuals. Symbiotic gut bacteria modulate the levels of BDNF to keep them normal.

-Normal functioning of the immune system: If the nervous system is not regulated properly it may begin attacking nerve tissue in a process known as neuroinflammation. The brains of autistic individuals have elevated concentrations of microglia (the brain’s immune cells) combined with other signs of inflammation. The human immune system is developed, programmed and regulated in part by symbiotic gut bacteria. Reductions in beneficial symbionts and reduced gut biodiversity cause inflammation that can progress to neuroinflammation. It is vital for the newborn infant to receive adequate starter cultures of probiotic bacteria from the mother and for these to thrive so that they can help with immune and brain development.

In light of modern birth and infant care practices, the rapid increase in autism is not surprising. Symbiotic bacteria are not acknowledged during most of the pregnancy and childbirth process and are not considered during healthcare decisions. Routine use of caesarian section births, often for “convenience and safety” in cases where there are no contraindications to normal vaginal birth, is the first major insult to the new infant’s microbiome. The vaginal canal provides a big starter culture that children born by c-section do not receive. The next boost to the infant microbiome is breastfeeding and skin-to-skin contact, both of which are not considered when a newborn is whisked away by attending nurses and physicians. When breastfeeding is explained as “an option” instead of “vitally necessary,” mothers are less likely to breastfeed their infants. Of course, sometimes c-sections are necessary, and it is possible to have medical reasons not to breastfeed. Understanding the significance of all these factors helps, so that probiotics, skin to skin contact and the remaining strategies can be properly utilized to help the developing microbiome and brain.

One of the most poignant causes of initial reductions in vagal tone come from the autonomic nervous system’s function as a “fight-or-flight” system. Consider the baby in the nine months prior to birth: a soft, warm, moist, dark and relatively quiet environment exists in the womb. Vagal tone is “relaxed” tone-so consider what happens when childbirth occurs in a brightly lit exam room with a multitude of voices and electronic sounds, and the newborn is removed from the mother’s warmth and examined, reflexes tested, held upside down, and injected with several vaccinations. The effect to the baby’s autonomic nervous system is to trigger a full fight-or-flight panic response, effectively supressing any vagal tone present. Commercial formula is frequently provided, reducing or eliminating the benefits of breastfeeding and instead using sugar-laden formula that encourages the overgrowth of harmful bacteria. The human body and its symbionts are not evolved to handle the consumption of “acellular carbohydrates” or simple sugars not in fruit or vegetable form.

When all of the above factors are considered, where are we heading as a species? Subsequent generations born and raised with such methods will be less able to care for new infants due to reduced emotional expression, reduced symbiont diversity and potentially forgetting “the old ways” that have worked successfully for millenia. Until parents and their physicians learn, acknowledge and promote a healthy microbiome, the health of babies and the incidence of autism may be fated to continue in the wrong direction.

References:

http://www.ncbi.nlm.nih.gov/pubmed/24709243
http://www.ncbi.nlm.nih.gov/pubmed/24500031
http://www.ncbi.nlm.nih.gov/pubmed/21683077
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2556849/
http://www.ncbi.nlm.nih.gov/pubmed/24614401
http://www.ncbi.nlm.nih.gov/pubmed/18295898
http://www.ncbi.nlm.nih.gov/pubmed/24639668
http://www.ncbi.nlm.nih.gov/pubmed/24566540
http://www.ncbi.nlm.nih.gov/pubmed/22826636
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3945747/
http://www.ncbi.nlm.nih.gov/pubmed/23139216