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Webinar #2-- Lets Start At The Beginning: Birth To One Year

Guy Daniels
Onegevity

Webinar #2-- Listen and learn as Guy Daniels, head of medical education at Onegevity, talks about maternal and prenatal health and how the microbiome is shaped from birth through the first months of life. This is a must-listen for any family who is pregnant or trying to conceive, as the microbiome research is discussed in great detail regarding the mode of delivery, breastfeeding, and early introduction of table foods. 



Guy Daniels:                      00:00                    Welcome to Webinar number two in our in-depth series on the microbiome. I'm Guy Daniels-- head of medical education at Onegevity and today's webinar's entitled, "Let's Start At The Beginning." Now, although we can't go back in time and change for ourselves what we'll be reviewing today, it does give us an excellent foundation for moving forward and if in fact you or a loved one is pregnant or trying to conceive, or if any of the other topics mentioned within this webinar apply to you, then it will most certainly be of value. Today we'll tackle briefly the impact of prenatal stress on the microbiome. We'll spend a fair amount of time on the vaginal microbiome, mode of delivery, and breastfeeding. And lastly, we'll briefly touch on the introduction of foreign proteins into the infant's gut.

Guy Daniels:                      00:46                    Research has shown that prenatal stress predisposes infants and children to premature birth, low birth weight, Eczema, asthma, impulsivity, anxiety, ADHD, and cognitive development, presumably via an impact on the microbiome. With this in mind, these Dutch researchers show that prenatal stress, as measured by a variety of surveys and to include salivary cortisol was strongly, persistently associated with the inference of microbiota composition. When they measured nine different infant fecal samples spread over the first 110 days of life, they found that a combination of high reported stress and high cortisol was related to significantly higher relative abundances of proteobacteria groups known to contain pathogens and lower relative abundances of good lactic acid bacteria and bifidobacteria. This imbalance was correlated with more infant gastrointestinal symptoms and allergic reactions. As a helpful side note, this combination has been associated with increased crying and infants, which makes sense. If there are little bellies are constantly upset, then they may be too. This is illustrated by the figure to the right. On the left side is the low-stress group A with more potential beneficial bacteria like bifidobacteria in green and fewer taxa, which could be opportunistic pathogens from the phylum and proteobacteria in red. You'll see that this is reversed in the high-stress group. B to the right.

Guy Daniels:                      02:21                    We have evolved with the vaginal delivery as our first inoculation in life. This initial exposure is of significant importance, and as we'll see in the slides to follow.

Guy Daniels:                      02:32                    Therefore, we must first look at what this entails, and we start with a landmark study out of North America. This is not a pregnancy study but purely a vaginal health study based on the premise that the human vaginal Microbiota seems to play a key role in preventing a number of urogenital diseases such as bacterial vaginosis, yeast infections, sexually transmitted infections, urinary tract infections, and HIV infection. Interestingly, the researchers were able to categorize the results from these 396 woman who represented four ethnic groups, into five communities. 73% of the subjects were dominated by one or more species of lactobacillus. This is generally a good thing. Without getting too immersed, the two standouts were as follows, communities in Group 1, which occurred in 26% of the women sampled were dominated by a Lactobacillus crispatus. This group had the lowest vaginal pH-- at four. This is a good thing. On the other hand, Group 4, which comprised 27% of the subjects, had a significantly different composition. It consisted of a large, diverse group of bacteria with a much higher pH-- that of 5.3 this yields dramatic differences in the bacteria that can reside in the vagina and although in the human gut microbiome, diversity is considered to be a good thing, when it comes to the vagina, and as you'll learn the infant microbiome, this is not necessarily true.

Guy Daniels:                      04:03                    This 2015 study examined 3,767 specimens from 40 women during pregnancy and post-delivery. Their results supported the results from our previous slide. The big takeaways being that Group 1, the one dominated by the lactobacillus crispatus, the group with the lowest Ph was the more stable, whereas Group 4 the one dominated by a variety of species, the higher ph group was less stable. So why is this important? Because a more stable, lower pH environment is protective against other bacteria which are considered opportunistic pathogens, meaning that even though they may be present in the gut or in this case in the vagina, instead of being held in check by a stable healthy microbiome, they take advantage of conditions that suit them, and create havoc. This plays a role in bacterial vaginosis, which in turn plays a role in delivery. For example, a number of studies show an association between bacterial vaginosis and preterm birth, like in this 2014 study with 1,268 African American subjects and 416 of European ancestry.

Guy Daniels:                      05:10                    The key takeaways here are one, African American woman are twice as likely to be diagnosed with bacterial vaginosis in our choices like to experience preterm birth. Two, bacterial vaginosis is characterized by a shift in the vaginal of microflora away from a low diversity profile predominated by lactic acid-producing bacteria, to a high diversity profile in which as producing bacteria are the minority. Three, bacterial vaginosis predisposes women to serious health issues including pelvic inflammatory disease, increased risk of acquisition and transmission of HIV, and other sexually transmitted diseases. Four, and lastly, they too support the finding from the landmark study we discussed earlier and added two more points. One, that lactobacillus iners is the least stable of the lactobacillus species, probably due to not having as robust production of lactic acid as compared to its lactobacillus counterparts. And the other unique finding here is that they added two more groups into the five previously established. These two additional major vaginal microbiome profiles are dominated by culprits in bacterial vaginosis and were found in a high proportion of samples from non-pregnant African American woman.

Guy Daniels:                      06:26                    This study here illustrates an important concept known as translocation. This simply means that bacteria are able to move from one body part to the other. This has been known for years and was shown in at least one study which labeled a probiotic. That probiotic was given orally, but when the vaginal microbiome was analyzed, the labeled probiotic showed up on the analysis. And this study here before us, the researchers looked at two species of bifidobacteria and showed that whether they came from the gut or the vagina, they were for all intents and purposes, genetically identical. We also know from animal data that as the pregnancy progresses, translocation increases. The point here is, it's possible to address the vaginal microbiome by first tackling your gut microbiome by food, supplements, and other considerations.  Whether healthy or not, you only get one shot at your newborn's first inoculation and as we'll see in the coming slides, that's a pretty important thing.

Guy Daniels:                      07:24                    Many newborns don't get a vaginal inoculation at all. In fact, according to this CDC data from 2015 fully one-third of U.S. deliveries are via C section. When I first saw this data a couple of years ago, I was surprised, but we don't even lead the pack globally. Depending on the reference, the country, the clinic, or the date, rates of c-section can be drastically higher. This is not a good trend overall. While a number of c-sections are performed for obstetrical indications, many are simply due to maternal request, as it is estimated that only 15% of births require c-section delivery to protect the health of the mother or baby. The problem with these increasing rates is the lack of vaginal inoculation for the newborn, and this is associated with significantly higher rates of gastroenteritis. Allergies of all sorts, celiac disease, and a 19% increased risk of developing type one diabetes. And from this paper, we can add significantly increased risks of systemic connective tissue disorders, juvenile arthritis, inflammatory bowel disease, immune deficiencies, and leukemia to c-section deliveries. Not to mention the fact that it becomes a standard procedure to give prophylactic antibiotics to a woman delivering by cesarean. Whether this plays an important role in the inoculation remains to be seen, as the data is conflicted.

Guy Daniels:                      08:48                    So what bacteria are inoculating the guts of these c-section babies? Studies show bacteria from the hospital room and skin are among the first inhabitants. In this study, the researchers assessed the gut microbiomes of 98 Swedish mothers and their infants during the first year of life, 15 of whom were delivered via c-section. They used metagenomic shotgun sequencing to assess the bacteria, the analysis that we use, and as you'll see, it adds a new level to our knowledge. For example, the average newborn microbiome had over 90% prevalence of genes involved in resistance against several antibiotics and the microbiome of infants delivered by c-section tended to contain a greater portion of antibiotic-resistant genes compared to vaginally delivered inference. This ability to dive into the genetic content of the microbiome is one of the benefits of our technology.

Guy Daniels:                      09:42                    If we look at the figure to the right from this Venezuelan study, it will visually give you an idea of the differences of what's going on at such a microscopic level. As you can see illustrated in blue, C-section infants had a gut microbiome that clustered around their mother's skin microbiome, whereas vaginally delivered infants in pink and red had one which clustered around their mother's vaginal microbiome. A skin microbiome is not going to be helpful for the gut. With all this in mind, these researchers went about inoculating c-section infants, with vaginal swabs post-delivery. As you can see from the figure to the right, when looking at two genera, Bacteroides and Lactobacillus, both of which should be present in the infant gut microbiome, the bacterial communities of newborns delivered by c-section can be partially restored to resemble that of vaginally delivered babies. Although somewhat effective, this is not practical, which brings us to the importance of breastfeeding.

Guy Daniels:                      10:41                    Breastfeeding is so important that the American Academy of Pediatrics recommends exclusive breastfeeding for at least the first six months of life. That is to say-- no other foods. Why? Because numerous studies show breastfeeding is correlated to reduced infant mortality, lower incidence of infectious diseases, enhance immune response, protection for infants against diarrhea, reduce the risk for post-neonatal death, reduce long-term risk for obesity, reduce incidents of narcotizing enterocolitis, better cognitive development, better growth, and overall health outcomes. Now, there are a number of highly beneficial components to human breast milk, but we'll only focus on two: the bacteria within and what are called human milk oligosaccharides, HMOs for short. As you will see from this diagram, water is the largest single component, but among the solo components where the value really is in breast milk, the third-largest is these HMOs. HMOs are nondigestible to us. As you recall from the last webinar, we possess only 17 digestive enzymes, whereas the bacteria in our gut possesses thousands. These HMOs are fuel for bacteria. And this fuel feeds primarily good bacteria, so they can thrive and create a favorable environment.

Guy Daniels:                      12:00                    So ask yourself-- why would millions of years of evolution drive us to consume so much energy to produce this component, which only has nutritional value to the bacteria in our guts? The gut microbiome must have paramount importance, and as you'll start to gather, it does. In total HMOs offer over 200 individual structures in various forums, but in the end they're essentially lactose and other sugars linked by bonds that we can't break, but our bacteria can.

New Speaker:                    12:31                    Bifidobacteria like the kinds we've taken probiotics particularly thrive on HMOs, at least three in particular, and especially one bifidobacterium infantis. In fact, studies show that bifidobacteria can account to 70 to 80% of the total bacteria in feces from breastfed babies. And the good news is that the cesarean born infants who are breastfed retain a high level of bifidobacteria, highlighting the importance of breastfeeding to select for protective gut microbiota in the infant.

Guy Daniels:                      13:06                    Bifidobacterium infantis is critical in establishing a healthy infant microbiome. Data shows it has anti-inflammatory properties through various mechanisms, produces beneficial short-chain fatty acids for other bacteria to feed upon, and reduces the levels of opportunistic pathogens in the gut. Taxa you'll eventually become familiar with, which include those within the phylum proteobacteria and even more specifically the family Enterobacteriaceae. Now bifidobacteria are a normal inhabitant of the vaginal microbiome. But how does an infant delivered via C-section get bifidobacteria into their gut? If you look at table one to the right, you'll see the nine most common genera found in breast milk, among the 200 plus bacterial species found to date-- and bifidobacteria is not in that list. Flaws in studies attributed to bacteria from mother's skin at the nipple or retrograde oral backflow during breastfeeding count for a fair number, but yes, bifidobacteria and other beneficial taxa are found in breast milk. How do they get there? No one really knows, but here's an interesting theory with data to back it up. Identical strains of belonging to the genera Bifidobacterium, lactobacillus, enterococcus, and staphylococcus have been detected in neonate feces, maternal milk, and the maternal feces which are assumed to be transferred from mother to neonate by breastfeeding via what's called the bacterial enteral memory pathway. It is believed that bacteria may translocate from the maternal gut by components of the immune system and subsequently circulate to the lactating memory gland via lymphatic and blood circulation. This makes sense as the bacteria in the maternal gut and breasts are genetically identical.

Guy Daniels:                      14:52                    Another proven method of microbiome transfer during vaginal delivery is due to contact with the paternal fecal matter. This results in the transfer of beneficial bacteria, but also ones such as Escherichia, which we consider opportunistic pathogens. In fact, in the first few days after birth, the intestine is colonized by a diverse microbial population. Remember that this isn't necessarily a good thing for an infant, but it becomes more stable in time, especially with breastfeeding. At birth, the infant's gut contains a high oxygen environment in which facultative anaerobes can thrive. The gradual oxygen consumption by these bacteria combined with the beneficial and modulating activity of taxa such as bifidobacteria, result in the stable gut.

Guy Daniels:                      15:38                    As mentioned previously, a number of studies have associated the microbiome more specifically a dysbiotic microbiome with atopic diseases such as asthma and eczema. As the incidence of allergy among infants in Japan has been skyrocketing and armed with the Canadian food sensitivity study showing an over-representation of Enterobacteriaceae-- that's the family of bacteria full of opportunistic pathogens, these Japanese researchers followed 56 infants for up to three years analyzing their microbiome. Not surprisingly, they found that those not suffering from allergy represented by light green had different microbiomes from those suffering from an allergy-- the orange like color. Those with allergy had fewer lactic acid-producing bacteria, fewer bacteria associated with breastfeeding, and fewer bacteria which thrive off the metabolites of these bacteria, a process referred to as cross-feeding, which we'll get to in time. The allergy-infants also had a remarkable over-representation of unclassified Enterobacteriaceae. Again, that's this misbehaving family.

Guy Daniels:                      16:46                    If you recall I mentioned earlier how the American Academy of Pediatrics recommends at least six months of exclusive breastfeeding before the introduction of foreign proteins. Well, no other protein is introduced earlier than that of dairy. So if you're not breastfeeding or not doing it exclusively, then odds are you're using a dairy-based product. I just want you to know that there are numerous studies going back many years associating dairy consumption with type one diabetes. That's type one the autoimmune version, not type two. I'm not going into detail about the various protein and peptide culprits found in cow's milk, but I will say that although there's a genetic component, which at least one identical twin study shows to be at most a third of the time, there is a huge lifestyle component. If you look at figure three, the countries with the highest consumption of dairy products also have the highest rates of type one diabetes. In a separate Finnish study, children who consumed the most milk had over five times the risk of developing type one diabetes versus the lowest consumers. So, the factors at play are the mode of delivery, the early introduction of dairy into an immature gut, the quantity and type of dairy consumed, and other factors such as enterovirus infection. This autoimmune response has to do with dysbiosis, inflammation, intestinal permeability, and genes. These risks are present in adults as well and manifest themselves in various ways, all of which we'll review in time.

Guy Daniels:                      18:20                    I hope this helps illustrate the importance of your microbiome. And although we can't go back in time for you, if you feel that correcting your gut microbiome is in order, there are steps you can take to support that. If you're interested, you can stay tuned as I publish these webinars. Or the quickest solution is to order a kit at onegevityhealth.com and take advantage of our expertise now. As for today, you've been exposed to a number of key concepts, which will remain true through the series.

Guy Daniels:                      18:47                    The microbiome plays an enormous role in multiple conditions. The pH balance and the opportunistic pathogens that thrive in dysbiosis are of paramount importance. Whole-genome sequencing, i.e. shotgun metagenomics, is the latest evolution in assessing the microbiome that provides us with additional layers of valuable data.

Guy Daniels:                      19:09                    Our next webinar will be on IBS, which will also include undiagnosed chronic diarrhea and or constipation. This has relevance for some 40 to 50 million Americans and as we completed a successful trial of IBS last year, we speak from a great deal of experience. So until next time.