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Experiment: Cutting the Vagus Nerve and Introducing Oxytocin

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Experiment: Cutting the Vagus Nerve and Introducing Oxytocin

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The proposed experiment will ensure that the observed results are indeed independent of any influence from the microbiota. As the vagus nerve allows the gut and brain to send signals to one another, it will be necessary to cut it so that the two areas are no longer communicating (23). This allows us to conclude that the oxytocin administered to these mice is acting without any input or output from gut bacteria. Additionally, it should be cut from birth to control for the possibility that any interaction between the two areas causes the gut bacteria to induce lifelong phenotypic changes in the brain.

The two conditions in this experiment will be 1) MHFD offspring + cut vagus nerve (experimental) and 2) MHFD offspring + intact vagus nerve (control). Both mice will be administered oxytocin intranasally and then placed in both a reciprocal social interaction and a three-chamber test for sociability and social novelty after 30 min to assess social behaviours. One day later, the VTA will be tested for evidence of LTP by 1) inducing an EPSP and 2) measuring AMPAR/NMDAR ratios. If, as expected, both conditions show LTP after oxytocin administration and the subsequent social interaction, then the results Buffington et al. (2016) reported are bolstered with stronger evidence. It would support the hypothesis that the role of L. reuteri is simply to increase oxytocin levels in the PVN, paving the way for it to reverse characteristic deficits after a social interaction. As the vagus nerve is cut in these mice, there is no known way that the gut bacteria could have influenced this process, meaning that only oxytocin and social interaction are necessary for social deficits to be reversed in MHFD offspring.

If these results are not observed, however, and MHFD offspring without a functioning vagus nerve still exhibit social deficits after oxytocin treatment, then the authors’ hypothesis about oxytocin is rejected and furthermore, it complicates their overall claims. A possible reason for such results is that communication between the brain and the gut through the vagus nerve was a confounding factor in their experiment. In this situation, introducing oxytocin intranasally may have normally induced changes in the brain that triggered communication with the gut in order for social interaction to successfully induce LTP. As the control condition has an intact vagus nerve, this back-and-forth signaling would have allowed for the observed reversal of social deficits, which would indicate that the methodology in the Buffington et al. (2016) paper led to inaccurate results. Moreover, these findings would contradict their proposed sequential mechanism of L. reuteri increasing oxytocin, leading to LTP occurring in the VTA after social interaction. Instead, it would appear that L. reuteri is only necessary to increase oxytocin levels initially and that any composition of microbiota is sufficient to carry out the process beyond that point. Additionally, it would show that the process is not entirely linear, with oxytocin feeding back to the gut, and thereby requiring both components working in unison for LTP to occur in social interactions and reverse deficits.

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Journal Articles
(1) Buffington SA, Di Prisco GV, Auchtung TA, Ajami NJ, Petrosino JF, Costa-Mattioli M. 2016. Microbial reconstitution reverses maternal diet-induced social deficits in offspring. Cell. 165:1762-1775.

(2) Bresnahan M, et al. 2015. Association of maternal report of infant and toddler gastrointestinal symptoms with autism: evidence from a prospective birth cohort. JAMA Psychiatry. 72(5):466-474

(3) Bruce-Keller AJ, Fernandez-Kim S-O, Townsend RL, Kruger C, Carmouche R, Newman S, et al. 2017. Maternal obese-type gut microbiota differentially impact cognition, anxiety and compulsive behavior in male and female offspring in mice. PLoS ONE 12(4): e0175577.

(4) Caplin, Maya. “Lactobacillus reuteri.” ProBiotics America, 31 Oct 2016, https://probioticsamerica.com/lactobacillus-reuteri/

(5) Connolly N, Anixt J, Manning P, Ping DL, Marsolo KA, Bowers
K. 2016. Maternal metabolic risk factors for autism spectrum disorder - An analysis of electronic medical records and linked birth data. Autism Res.

(6) Friedman JE. 2016. The maternal microbiome: cause or consequence of obesity risk in the next generation? Obesity. 25(3):497-498

(7) Fuchs F, Senat MV, Rey E, Balayla J, Chaillet N, Bouyer J, Audibert F. 2017. Impact of maternal obesity on the incidence of pregnancy complications in France and Canada. Science Reports. 7:10859

(8) Galley JD, Bailey M, Dush CK, Sullivan SS, Christian LM. 2014. Maternal obesity is associated with alterations in the gut microbiome in toddlers. PLoS. 1(9).

(9) Gareau MG, et al. 2011. Bacterial infection causes stress-induced memory dysfunction in mice. Gut. 60(3):307-317

(10) Hamptom T. 2016. Maternal obesity affects sociality of offspring by altering gut bacteria. Journal of American Medical Association. 316(5):484.

(11) Kang DW, et al. 2017. Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study. Microbiome 5(10): https://doi.org/10.1186/s40168-016-0225-7

(12) Krakowiak P, Walker CK, Bremer AA, Baker AS, Ozonoff S, Hansen RL, Hertz-Picciotto I. 2012. Maternal metabolic conditions and risk for autism and other neurodevelopmental disorders. Pediatrics. 129(5)

(13) Lieshout RJ, Taylor VH, Boyle MH. 2011. Pre-pregnancy and pregnancy obesity and neurodevelopmental outcomes in offspring: a systematic review. Obesity Reviews. 12(501):548-559

(14) Ma J, Prince AL, Bader D, Hu M, Ganu R, Baquero K, Blundell P, Harris RA, Frias AE, Grove KL, Aagaard KM. 2014. High-fat maternal diet during pregnancy persistently alters the offspring microbiome in a primate model. Nat. Commun. 5: 3889

(15) Maftei O, Whitrow MJ, Davies MJ, Giles LC, Owens JA, Moore VM. 2015. Maternal body size prior to pregnancy, gestational diabetes and weight gain: associations with insulin resistance in children at 9-10 years. Diabetes Med 32(2):174-80

(16) Mehta SH, Kerver JM, Sokol RJ, Keating DP, Paneth N. 2014. The association between maternal obesity and neurodevelopmental outcomes of offspring. Journal of Pediatrics. 165(5):891-896

(17) Parashar A, Udayabanu M. 2016. Gut microbiota regulates key modulators of social behaviour. European Neuropsychopharmacology. 26(1):78-91.

(18) Penagarikano O, Abrahams BS, Herman EI, Winden KC, Gdalyahu A, Dong H, Sonnenblick L, Gruver R, Almajano J, Bragin A, Golshani P, Trachtenberg JT, Peles E, Geschwind DH. 2011. Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities and core autism-related deficits.  National Institute of Health. 147(1):235-246

(19) Reynolds LC, Inder TE, Neil JJ, Pineda RG, Rogers CE. 2014. Maternal obesity and increased risk for autism and developmental delay among very preterm infants. Journal of Perinatology. 34:688-692

(20) Selimbeyoglu A, Kim CK, Inoue M, Lee SY, Hong ASO, Kauvar I, Ramakrishnan C, Fenno LE, Davidson TJ, Wright M, Deisseroth K. 2017. Modulation of prefrontal cortex excitation/inhibition balance rescues social behaviour in CNTNAP2-deficient mice. Science Translational Medicine 9:1-10

(21) Sullivan EL, Nousen EK, CHamlou KA. 2014. Maternal high fat diet consumption during the perinatal period programs offspring behavior. Physiology & Behaviour 123: 236-242

(22) Vuong HE, Hsiao EY. 2017. Emerging Roles for the Gut Microbiome in Autism Spectrum Disorder. Biological Psychiatry. 81:35-37

(23) Wang X, Wang BR, Zhang XJ, Xu Z, Ding YQ, Yu G. 2002. Evidences for vagus nerve in maintenance of immune balance and transmission of immune information from gut to brain in STM-infected rats. World J Gastroenterol. 8(3):540-505

(24) White CL, et al. 2009. Effects of high fat diet on Morris maze performance, oxidative stress, and inflammation in rats: contributions of maternal diet. Neurobiol Dis. 35(1):3-13

(25) White CL, Purpera MN, Morrison CD. 2009. Maternal obesity is necessary for programming effect of high-fat diet on offspring. Am J Physiol Regul Integr Comp Physiol. 296(5):464-72

Youtube Video Links
(1) 16 S rRNA Gene Sequencing Service by LC Sciences
https://www.youtube.com/watch?v=c6w1uZL0HjE

(2) Poop Transplants by MinuteEarth
https://www.youtube.com/watch?v=Dim7YXYlRm0

(3) Shotgun Sequencing Simple Animation by Lorna Daly
https://www.youtube.com/watch?v=B_ebMtsGSb0

(4) The Party: A Visual Experience of Autism - 360 Film
https://www.youtube.com/watch?v=OtwOz1GVkDg

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Is the Obesity-Autism Link Self-Perpetuating?

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Is the Obesity-Autism Link Self-Perpetuating?

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The disparity in obesity prevalence between adolescents with autism spectrum disorder (ASD) and those without increases with age, according to new and unexpected findings from a study of US children.

Between the ages of 10 and 17, obesity prevalence halved (from 19.1% to 8.3%) among children without ASD, whereas it remained more or less consistent or was higher among children with ASD (increasing from 20.0% at age 10 to 22.1%), report Aviva Must, PhD, chair of the department of public health and community medicine, Tufts University School of Medicine, Boston, Massachusetts, and colleagues.

The researchers believe that this is the first study to demonstrate the increasing disparity in obesity prevalence between adolescents with ASD and those without. The work is published online October 5 in Childhood Obesity.

Overall, significantly more adolescents with ASD were obese (23.1%) compared with the same-age peers without ASD (14.1%).

"In the typical [non-ASD] population, the prevalence of obesity declined in adolescence, which isn't a new finding in itself, but in the adolescents with ASD we saw that the prevalence of obesity remained constant - this was surprising," Dr Must highlighted.

"Both the prevalence of autism and likewise the prevalence of obesity have been rising since 1980, with rates in the US tripling among children aged 6 to 11 and quadrupling among adolescents," Dr Must told Medscape Medical News.

"In this study, we wanted to understand how the prevalence of obesity changes with age in children with autism and to compare that with typically developing children," she explained.

Kids With Development Disabilities at Increased Risk of Obesity

The National Survey of Children's Health (NSCH) data set, a nationally representative survey conducted by the Centers for Disease Control and Prevention's National Center for Health Statistics, was used for the study.

Dr Must explained that this contains information on almost 100,000 children aged 0 to 17 including parents' reports of their children's health. "The NSCH releases height and weight only of children over 10 years, so our study looked at this age group."

Although the prevalence is increasing, autism is still relatively rare, and as such, a very large data set is needed to ask questions and explore associations in this population. In total, 43,777 children with information on both ASD and weight status were available for analysis, with figures drawn from the 2011-2012 NSCH data set.

Dr Must reflected on why children with developmental disabilities, including those with ASD, appear to be at elevated risk for obesity. "Some core features of autism and its treatment might increase the risk of obesity, especially as children age."

She also pointed out their surprise in finding that in the typical population, the prevalence of obesity declined in adolescence.

"We started out at age 10 with a disparity between the two groups; this disparity grew with...age but it isn't because the children with autism were becoming more obese but because the prevalence of obesity in those without autism was declining."

Senior author on the paper was Linda Bandini, PhD, associate professor at the University of Massachusetts Medical School's Eunice Kennedy Shriver Center; clinical professor, department of health sciences, Boston University; and director, Healthy Weight Research Network.

She observed that a number of factors can contribute to the increased prevalence of obesity in children with ASD, including sensory sensitivity, the need for routine or sameness, behavioral rigidity, use of food as a reward, mealtime stress, and parental stress.

"When it comes to energy expenditure, exercise for many teens comes in the form of competitive sports, in which children with developmental disabilities are less likely to take part. Another reward and calming technique parents of children with ASD have reported using is television, which may contribute to higher levels of sedentary behavior," she continued.

Dr Must added that some medications for ASD are also known to be associated with weight gain: "We can't have a conversation about what is going on without mentioning the role of medication."

Find Out Why ASD Associated With More Obesity, and Tackle the Issues

Looking ahead, Dr Must said that understanding more about the decline in obesity in the typical adolescent population might help researchers understand more about how to replicate that in children with autism.

"The findings, as they stand, underscore a need to explore further the risk factors and facilitators of better behaviors. If the medication turns out to be a big piece of it, then there's a role for the healthcare system in terms of anticipatory guidance...telling parents to be vigilant of weight gain. Depending on which factors turn out to be most impactful, this will lead to the most appropriate intervention."

She also pointed out that there is a need to think about the long-term consequences of chronic disease. "If someone becomes diabetic at 35 and they have behavioral difficulties, then this can interfere with the ability to live independently."

Commenting on the paper, Dr Judith Brown, PhD, head of knowledge at the National Autistic Society, United Kingdom, said that the findings add to evidence that autistic children and adults can have different health outcomes and that "the vital next step is to find out why and to design suitable responses."

"It could be that routine or restricted diets have an impact, because of autistic people's sensory sensitivities or need for a predictable routine. We also know that autistic people can struggle to play sports, either due to motor issues, dyspraxia, or feeling intimidated by the social element, which may discourage them from doing exercise."

This research was performed as part of the Healthy Weight Research Network for children with autism and developmental disabilities, which is a federal government-funded program. The authors have declared no relevant financial relationships.

For more diabetes and endocrinology news, follow us on Twitter and on Facebook.

Childhood Obes. Published online October 5, 2016. Abstract

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Teens With Autism More Likely to Be Obese, Stay Obese

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The disparity in obesity prevalence between adolescents with autism spectrum disorder (ASD) and those without increases with age, according to new and unexpected findings from a study of US children.

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Paternal Obesity and Autism? An Anthropological Perspective

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Paternal Obesity and Autism? An Anthropological Perspective

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One of the many original and counter-intuitive predictions to which the imprinted brain theory gives rise is the suggestion that rising living standards may be a factor in explaining the so-called " autism epidemic" (first made by me in my book, The Imprinted Brain, in 2009, and repeated in a post on this site).

IGF2 is the paradigmatic imprinted gene, coding for a major growth factor, and is normally only expressed from the father's copy. But in mice, a maternally active imprinted gene, Igf2r, contradicts its effects, mopping up the growth hormone, as explained in an earlier post. IGF2 has been found to be down-regulated in the offspring of women who have been starved during pregnancy, and so it would not be surprising if the same growth-promoting gene were up-regulated in the children of mothers who were fed better than normal. Indeed, a recent study using data from the Avon Longitudinal Study of Parents and Children cohort reported that "a prenatal maternal high-fat and -sugar diet may alter the DNA methylation status of the IGF2 gene at birth, which in turn, may increase risk for a range of psychiatric and health disorders." Furthermore, and as I noted in a previous post, a huge study of 1.7 million Danish health records established an unquestionable link between birth size and risk of mental illness: larger babies were more prone to ASD, but smaller ones to PSD, just as predicted by the imprinted brain theory.

Now a new meta-analytic study reports that

compared with children whose mothers were at normal weight, children born to overweight and obese mothers have a 28% and 36% higher risk of developing ASD, respectively. Maternal underweight was not associated with increased ASD risk. A linear dose-response relationship was found, with the risk of ASD increasing by 16% for each 5 kg/m2 increment in maternal BMI compared with that of normal weight.

Source: Wikimedia commons

BMI stands for body mass index and is defined as your weight divided by your height squared, yielding the diagram left. The term was coined in 1972 by the nutrition and public health researcher, Ancel Keys, who explicitly stated that it was only appropriate for population studies and ought not to be used for individual diagnosis.

The problem to which the latter can give rise is illustrated by some well known Hollywood actors, all at the peak of their careers and all of whom according to The Sunday Times of July 28th 2002 had BMIs over 30, and were therefore "obese:" Arnold Schwarzenegger, 257lb, 6ft 2ins = BMI 33; Tom Cruise, 201lb, 5ft 7ins = BMI 31.5; and Sylvester Stallone, 228lb, 5ft 9ins = BMI 33.7.

Iconic modern males may not seem directly relevant, and you can get round the problem by having different BMIs for males and females. Nevertheless, a prehistoric female icon like the Dolní Věstonice Venus, a figurine dating from 28,000 years ago and illustrated left, is clearly in the "obese" quadrant for BMI. However, her waist-hip ratio (WHR) is quite another matter. As I explained in a previous post, WHR correlates strongly with fat distribution in the body. And as this figurine also illustrates, oestrogens stimulate women to deposit fat on the buttocks, thighs and breasts. WHR is similar for the sexes before puberty, but afterwards women's range from 0.67-0.8, whereas men's go from 0.85-0.95. Risk of obesity-related diseases such as diabetes, hypertension and heart disease vary with WHR, so that it is also a good indicator of health in this respect. Indeed, higher WHR indicates increased risk of death in women independently of weight. And as I also noted in the earlier post, lower WHRs in women correlate with higher IQs in their children. Interestingly, this figurine has a WHR estimated to be 0.7, which is the value preferred by judges of both sexes viewing female body profiles with differing weights and WHRs. So, whatever her BMI, this Venus's WHR is about right.

And as this supposed fertility fetish also suggests, fatness goes with fecundity: normal weight US women average 3.2 children, over-weight/obese 3.5. In the case of the Ache hunter-gatherers, the mean age at which women first gave birth was found to be the same as that at which they first reached mean weight for adult females in the population. Heavier women were also found to have more children, to have them more closely spaced, and to have children who survived better than did the offspring of lighter women. Since maternal investment in the developing foetus is principally in the form of nutrients, it is not surprising that it is the level of such nutrients stored in the mother's body-fat, in other words-which is critical to fertility. So sensitive is the female body to body weight variations that some women athletes can turn their sexual cycles on and off at will with just a three pound change in weight.

Even if restricted to populations as Keys intended, BMI is not as simple as it seems. The highest life expectancy in 2 million Norwegians was found in the "over-weight" part of the population, that is, those with BMI 26-28. The "ideally slim," with BMI 18-20 had lower life expectancy than the "obese" with BMI 34-36, while being "under-weight" (BMI<18.5) was associated with more excess death than BMI 30-35.

When explaining this to students, I used to speculate that the reason could be that heavier weight might stand a person in better stead in the face of surgery or serious illness later in life, never dreaming that this is exactly what would happen to me. Radical cancer surgery reduced my weight by 25%, my BMI from an "obese" 30 to a "normal" 22, and took 6 inches off my waist. Had I started with an ideal BMI, I would have ended up dangerously underweight. Furthermore, I only managed to stabilize my weight by means of eating the "unhealthy" fatty, starchy, and sugary diet blamed for obesity.

A 10-year WHO study of 140,000 people in 38 countries on 4 continents in 2001 saw increases in BMI associated with decreases in high blood pressure and cholesterol, concluding: "These facts are hard to reconcile" with the conventional wisdom, particularly in view of the fact that predicted increases in mortality due to obesity have not occurred, and life expectancy continues to improve along with increasing average body weight in industrialized countries. Indeed, in 2006, 20 obesity experts were quoted concluding that evidence that slothful lifestyle and junk food contribute to obesity is "largely circumstantial," while large-scale longitudinal studies of Californian women and Native American children have found no health gains or significant reductions in body fat due to "healthy diet."

In the view of J. Eric Oliver quoted in Scientific American for June 2005:

a relatively small group of scientists and doctors, many directly funded by the weight-loss industry, have created an arbitrary and unscientific definition of weight and obesity. They have inflated claims and distorted statistics on the consequences of our growing weights, and they have largely ignored the complicated health realities associated with being fat.

How fat you normally are is a matter largely determined by your genes: BMI of adopted children resembles biological, not adoptive parents, and twin studies suggest 70% BMI heritability, with shared environment having little or no effect. Race/ ethnicity is also a factor: in the US, Mexican-American women are 30% more likely than whites to be obese, and black women twice as likely.

Indeed, according to the thrifty gene theory, risk of type 2 diabetes and the "obesity" which often goes with it is an evolved factor to promote fat gain and efficient use of food in times of abundance, with survival value for periods of shortage. Lack of mass starvations in Europe since the 17th century could explain low incidence of diabetes among native Europeans thanks to selection against it, but the likelihood that the Pacific was peopled by the starved survivors of epic canoe voyages might explain why prevalence is so high among their descendants. Most notably, the incidence of this late onset disorder went from zero on the island of Nauru in 1952 to 41% in 2002, with two-thirds of all Nauruans over 55 being diabetic, and 70% being so over the age of 70 following the discovery of phosphates and the conversion of the islanders' life-style to an affluent Western one (above left).

The Nauru story epitomizes the truth that it is a question of nurture via nature, not the reverse, as is so often asserted. Nauruans' Western diet is indeed causing an epidemic of type 2 diabetes, but only because Nauruans are genetically predisposed to the disorder by way of being descended from founders who could put weight on to the point of being fat enough to survive starvation on canoes colonizing the Pacific.

Exactly the same is true of maternal "obesity" and risk of ASD. Modern life-styles and diet have unquestionably released more resources for development during gestation in many modern Western women, but this has been more to the benefit of the paternal genes in the foetus and placenta than to that of the maternal ones. As a result, a mother-no matter what her BMI-could righty blame a child's paternal growth-enhancing genes for most of its eventual growth and associated risk of ASD: in other words, the genes for whom she is effectively providing the proverbial free lunch, thanks to the fact that only the mother pays the biological costs of gestation and lactation. And of course, because such genes as IGF2 are normally expressed only from the father's copy, it is hardly surprising that paternal obesity has also been linked to risk of ASD. Indeed, as the meta-analysis I am quoting points out, "studies also suggested that when adjusted for paternal and other confounding factors, the risk of autism in children with obese mothers was attenuated."

(With thanks to Amar Annus for bringing this to my attention, and to Randy Jirtle.)

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"Obese" Mothers and Autism: Not As Simple As It Seems

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One of the many original and counter-intuitive predictions to which the imprinted brain theory gives rise is the suggestion that rising living standards may be a factor in explaining the so-called " autism epidemic" (first made by me in my book, The Imprinted Brain, in 2009, and repeated in a post on this site).

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Introduction The 16S rRNA gene is a highly conserved component of the transcriptional machinery of all DNA-based life forms and thus is highly suited as a target gene for sequencing DNA in samples containing up to thousands of different species.

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Female C57Bl6/J mice were separated into following either a high fat diet (MHFD; 60% fat, 20% protein, 20% carbohydrates) or a regular diet (MRD; 57% carbohydrates, 30% protein, 13.4% fat) for 8 weeks

Paired with adult males to produce offspring

After weaning at 3 weeks, MHFD and MRD offspring were both put on a regular diet before experiments were carried out

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Autism Today - George's Personal Experience

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Autism Today - George's Personal Experience

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In so many ways, nine-year-old George Yionoulis is like other boys his age. He likes Harry Potter, and watching cartoons. He has a creative side, whether it's drawing pictures by hand or making music or writing code. He's into dancing - usually with his whole body, at a moment's notice.

"He has to dance," George's mother Lisa Jolley says about her son. With a laugh, she remembers a time when he stopped to jam out with a group of buskers on the New York subway. Despite his enthusiastic dance moves, nobody took notice - "very New York" her mom recalls with a laugh.

George was also born with autism.

But after a video made by George and his family exploded into viral fame, millions of people around the world are learning not just that last fact but everything about his personality - the dancing, the music, the Harry Potter - and more, including the challenges he faces in his everyday life.
READ MORE: Family's heart-rending case prompts call for autism strategy: 'We are not alone'
Titled My Autism, the video features George as narrator, guiding the viewer through a look at his hobbies and his personality, through the lens of his autism.

It was intended to help his classmates better understand his condition.

"This video was made for an audience of 21 fourth graders," Jolley tells Global News from her home in Raleigh, N.C. "This was to show his class and his teacher...that he does know, he's very aware, he does know he has [autism]."

The video soon found a much wider audience than those 21 fourth graders after it was first posted on Nov. 27. As of now the video has amassed nearly 25,000 views on YouTube. It's also garnered attention from advocacy groups, media outlets, and even Hamilton creator Lin-Manuel Miranda.

"It's very cool, just to be transparent about it," Jolley said. "[To say] 'I've got this thing. It's just a part of who I am. And it might be the reason I dance, who knows?'"
LISTEN: 770 CHQR's Rob Breakenridge chats with Autism Calgary about George's method of sharing information and how to help classmates understand the challenges of autism
For the first couple years of his life, George's parents Lisa and Mike were not aware their son had autism. Their first indication that something was different about their son came when his speech seemed to be delayed.

At two years old, George's parents took him to a speech therapist. That's when they got the news.

"'Have you thought of autism?'" Jolley remembers hearing for the first time. "It was a blow to the gut. It was just completely out of left field."

The news changed the way they thought about their son - and how he sees the world.

"We the parents, we only think big picture. 'Is he going to graduate school? Is he going to get married? Is he going to have kids? Is he going to live on his own?' Big picture," Jolley said. "And what I've learned is [kids with autism] only see small picture...it changes you."

In the video, George tries to explain certain aspects of his personality and why he behaves the way he does. For instance, George warns against using metaphors like "take a seat" or "it's raining cats and dogs" because he's liable to take it literally.
READ MORE: CRA faces fresh criticism on disability tax credit, this time from autism group
He also explains how difficult it is to filter out sensory input, like lots of noises in a crowded room, or that it's difficult to make and keep eye contact.

"Like a lot of other kids with autism, I may not have been looking [at you] but that doesn't mean I wasn't listening," George explains.

The video doesn't shy away from some of the negative consequences of his autism, like the fact that he can become overwhelmed easily, or become easily frustrated by a mistake, or quick to anger when he feels ignored.

Portraying that balance was important for Jolley, who wanted to help her son make friends in his class but also didn't want to shy away from the truth about his autism.

"When it's bad, it's bad," Jolley said. "Make no mistake."

While the feedback on the video has been for the most part "overwhelmingly positive" according to Jolley, they have received some negative feedback as well.

"A lot of people focus on the physical, which is crazy," Jolley said. "[Comments like] 'Poor kid, his autistic and those teeth.' Like dude, he's nine! He still has so many baby teeth! Plus I love his teeth. There's an emoji which looks just like him!"

But perhaps the most touching part of the video comes from George's direct appeal to his classmates. In this moment, with locks of black hair falling across his bespectacled face, George echoes so many children who have ever felt outcast, misfit, misunderstood - alone.

"I like having fun, just like you. So if you ever see me playing by myself, it doesn't mean I don't want to play with you, too." George says.

"Don't be afraid to come ask me about it. No seriously, it's ok, just come ask me about it."

You can watch the full video here.

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Little boy's touching video explaining his autism to his classmates goes viral

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In so many ways, nine-year-old George Yionoulis is like other boys his age. He likes Harry Potter, and watching cartoons. He has a creative side, whether it's drawing pictures by hand or making music or writing code. He's into dancing - usually with his whole body, at a moment's notice.

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One of the Top 20 Neuroscience Articles of 2016!

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One of the Top 20 Neuroscience Articles of 2016!

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Summary: Researchers culture a strain of Lactobacillus reuteri from human breast milk and introduced it to mice. They discovered treatment with this bacterial strain appeared to rescue social behaviors. Source: Cell Press. The absence of a one specific species of gut bacteria causes social deficits in mice, researchers at Baylor College of Medicine report June 16, 2016 in Cell. By adding this bacteria species back to the guts of affected mice, the researchers were able to reverse some of their behavioral deficits, which are reminiscent of symptoms of autism spectrum disorders (ASDs) in humans. The investigators are now looking to explore the effects of probiotics on neurodevelopmental disorders in future work.
"Other research groups are trying to use drugs or electrical brain stimulation as a way to reverse some of the behavioral symptoms associated with neurodevelopmental disorders - but here we have, perhaps, a new approach," says senior author Mauro Costa-Mattioli, a neuroscientist at Baylor College of Medicine. "Whether it would be effective in humans, we don't know yet, but it is an extremely exciting way of affecting the brain from the gut."

The inspiration for the paper came from human epidemiological studies that have found that maternal obesity during pregnancy could increase children's risk of developing neurodevelopmental disorders, including ASDs. In addition, some individuals with ASD also report recurring gastrointestinal problems. With emerging research showing how diet can change the gut microbiome and how gut microbes can influence the brain, Costa-Mattioli and his co-authors suspected there could be a connection.

To begin, the researchers fed approximately 60 female mice a high-fat diet that was the rough equivalent of consistently eating fast food multiple times a day. They bred the mice daily and waited for them to bear young. The offspring stayed with their mother for three weeks and then were weaned onto a normal diet. After a month, these offspring showed behavioral deficits, such as spending less time in contact with their peers and not initiating interactions.

"First we wanted to see if there was a difference in the microbiome between the offspring of mouse mothers fed a normal diet versus those of mothers fed a high-fat diet. So, we used 16S ribosomal RNA gene sequencing to determine the bacterial composition of their gut. We found a clear difference in the microbiota of the two maternal diet groups," says first author Shelly Buffington, a postdoctoral fellow in Costa-Mattioli's lab. "The sequencing data was so consistent that by looking at the microbiome of an individual mouse we could predict whether its behavior would be impaired."

Buffington next tested whether the specific differences in the microbiome were causative factors underlying the social impairments in offspring of mothers fed a high-fat diet. Because mice eat each other's poop, the researchers housed the animals together so that they would acquire microbiota from their cagemates. When socially impaired three-week-old mice born to mothers on a high-fat diet were paired with normal mice, a full restoration of the gut microbiome and a concurrent improvement in behavior was observed within four weeks. The investigators concluded that one or more beneficial bacterial species might be important for normal social behavior. Fecal-transplant experiments in mice without microbiota (germ-free mice) provided causal evidence that an imbalanced microbial ecology in the mice born to mothers on a high-fat diet is responsible for their social deficits.

The investigators next wanted to know the specific bacterial species that could be affecting the social behavior of the mice. Whole-genome shotgun sequencing revealed one type of bacteria, Lactobacillus reuteri, which was reduced more than nine-fold in the microbiome of mice born to mothers on the high-fat diet.

"We cultured a strain of Lactobacillus (L.) reuteri originally isolated from human breast milk and introduced it into the water of the high-fat-diet offspring. We found that treatment with this single bacterial strain was able to rescue their social behavior," Buffington says. Other ASD-related behaviors, such as anxiety, were not restored by the reconstitution of the bacteria. Interestingly, the authors found that L. reuteri also promoted the production of the "bonding hormone" oxytocin, which is known to play a crucial role in social behavior and has been associated with autism in humans.

Can mom's diet during pregnancy impact offspring social behavior? In this video, Mauro Costa-Mattioli and colleagues at Baylor College of Medicine describe a potential link between mouse maternal diet-induced changes in the gut microbiome and autism-like social behavior in offspring.

The authors wondered whether the reward circuitry in the socially impaired mice was dysfunctional. "We found that in response to social interaction there was a lack of synaptic potentiation in a key reward area of the brain that could be seen in the normal control mice," Costa-Mattiol says. "When we put the bacteria back in the maternal-high-fat-diet offspring, we could also restore the changes in synaptic function in the reward circuitry."

The researchers believe that their work, which uses a human bacteria species to promote oxytocin levels and improve social behavioral deficits in deficient mice, could be explored as a probiotic intervention for the treatment of neurodevelopmental disorders in humans. "This is where the science is unexpectedly leading us. We could potentially see this type of approach developing quite quickly not only for the treatment of ASD but also for other neurodevelopmental disorders; anyway, this is my gut feeling," Costa-Mattioli says.

About this neuroscience research article

Others who contributed to the research include Gonzalo Viana Di Prisco, Thomas A. Auchtung, Nadim J. Ajami, and Joseph F. Petrosino, all at Baylor College of Medicine.

Funding: The research was supported by funding from the National Institutes of Health, the Alkek Foundation, and Baylor College of Medicine.

Source: Joseph Caputo - Cell Press
Image Source: This NeuroscienceNews.com image is credited to Costa-Mattioli et al./Cell Press
Video Source: The video is credited to Baylor College of Medicine.
Original Research: Full open access research for "Microbial Reconstitution Reverses Maternal Diet-Induced Social and Synaptic Deficits in Offspring" by Shelly A. Buffington, Gonzalo Viana Di Prisco, Thomas A. Auchtung, Nadim J. Ajami, Joseph F. Petrosino, and Mauro Costa-Mattioli in Cell. Published online June 16 2016 doi:10.1016/j.cell.2016.06.001

Cite This NeuroscienceNews.com Article

Abstract Microbial Reconstitution Reverses Maternal Diet-Induced Social and Synaptic Deficits in Offspring
Highlights
*Maternal high-fat diet (MHFD) induces behavioral alterations in offspring
*MHFD causes alterations in gut microbial ecology in offspring
*MHFD offspring show deficient synaptic plasticity in the VTA and oxytocin production
*L. reuteri treatment restores oxytocin levels, VTA plasticity and social behaviors

Summary
Maternal obesity during pregnancy has been associated with increased risk of neurodevelopmental disorders, including autism spectrum disorder (ASD), in offspring. Here, we report that maternal high-fat diet (MHFD) induces a shift in microbial ecology that negatively impacts offspring social behavior. Social deficits and gut microbiota dysbiosis in MHFD offspring are prevented by co-housing with offspring of mothers on a regular diet (MRD) and transferable to germ-free mice. In addition, social interaction induces synaptic potentiation (LTP) in the ventral tegmental area (VTA) of MRD, but not MHFD offspring. Moreover, MHFD offspring had fewer oxytocin immunoreactive neurons in the hypothalamus. Using metagenomics and precision microbiota reconstitution, we identified a single commensal strain that corrects oxytocin levels, LTP, and social deficits in MHFD offspring. Our findings causally link maternal diet, gut microbial imbalance, VTA plasticity, and behavior and suggest that probiotic treatment may relieve specific behavioral abnormalities associated with neurodevelopmental disorders.

"Microbial Reconstitution Reverses Maternal Diet-Induced Social and Synaptic Deficits in Offspring" by Shelly A. Buffington, Gonzalo Viana Di Prisco, Thomas A. Auchtung, Nadim J. Ajami, Joseph F. Petrosino, and Mauro Costa-Mattioli in Cell. Published online June 16 2016 doi:10.1016/j.cell.2016.06.001

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Single Species of Gut Bacteria Can Reverse Autism Related Social Behavior: Mouse Study - Neuroscience News

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Summary: Researchers culture a strain of Lactobacillus reuteri from human breast milk and introduced it to mice. They discovered treatment with this bacterial strain appeared to rescue social behaviors. Source: Cell Press. The absence of a one specific species of gut bacteria causes social deficits in mice, researchers at Baylor College of Medicine report June 16, 2016 in Cell.

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The combination of direct application of oxytocin and social interaction with a stranger mouse significantly raised the AMPA/NMDA receptor ratios and restores the LTP current

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Experiment 3: Effects of Direct Application of Oxytocin 

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Experiment 3: Effects of Direct Application of Oxytocin 

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After discovering that L.reuteri could restore oxytocin reactivity in the PVN – they wanted to see if direct oxytocin application could reverse behavioral deficits and LTP

After the injection of oxytocin intranasally, oxytocin alone was unable to restore LTP levels.

NEVERTHELESS...

A combination of both social interaction and oxytocin application was able to induce LTP in the VTA

This implies that oxytocin and dopaminergic system must work together to promote LTP for the processing of social relevant cues

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Buffington et al. 2016. Figure 5 (B,C,H)

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Buffington et al. 2016. Figure 5 (B,C,H)

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Interaction between the control (MRD) and a stranger mice induced LTP currents. However, with the MHFD mice, LTP was not induced. Only with the introduction of live L. reuteri were the LTP currents restored with the MHFD mice.

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Experiment 2: Effects of MHFD on LTP + Social Interaction 

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Experiment 2: Effects of MHFD on LTP + Social Interaction 

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Measurements of AMPA/NMDA receptor ratios were performed as well as records of excitatory postsynaptic potentials (EPSPs) during a reciprocal social interaction test with both groups (MHFD and MRD).

Social stimulation with a stranger mice within the MHFD group did not induce LTP in the VTA as seen through a reduced amplitude of the current. This was contrasted in the MRD group.

NEVERTHELESS...

Introduction of live (only) L. reuteri restored LTP when maternal high fat diet mice underwent social interaction

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(1) Using immunostaining for oxytocin (green dye), there was a reduction in the oxytocin-expressing neurons in the MHFD group in comparison to the MRD. All other neurons remained the same seen with the NeuN stain (red).
(2) With the introduction of L. reuteri, oxytocin-expressing neurons were restored.

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Experiment 1: Reduction of Oxytocin Expressing Levels + Restorations of the Same By L. reuteri 

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Experiment 1: Reduction of Oxytocin Expressing Levels + Restorations of the Same By L. reuteri 

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Using immunostaning techniques, the paraventricular nuclei (PVN) was visualized for their oxytocin-expressing cells and other contrasting neurons (using NeuN).

The maternal high fat diet (MHFD) mice had a REDUCED amount of oxytocin immunoreactive neurons in comparison to the maternal normal diet mice (MRD)

*This reduction was not due to a decrease in PVN neurons – as they remained the same with the NeuN staining

NEVERTHELESS...

With the introduction of L. reuteri (both heat killed or live) strain of bacteria, oxytocin immunoreactive neurons were restored.

This shows that maternal obesity can cause a reduction of oxytocin neurons, which can be restored with the introduction of L. reuteri.

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Buffington et al. 2016. Figure 4 (D, E) Three-chamber test track plots for MHFD + heat-killed L. reuteri (top) and MHFD + live L. reuteri (bottom). MHFD offspring treated with active bacteria showed regular social behaviour, as they preferred to interact with the stranger mouse in each test. Those treated with heat-killed bacteria, however, showed characteristic social deficits as they never showed a preference for either chamber.

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Buffington et al. 2016. Figure 4 (B) Three-chamber test results for all conditions. MHFD offspring treated with live L. reuteri showed restoration of normal social function, while other MHFD conditions continued to show social deficits. MRD offspring maintained regular social behaviour regardless of treatment.

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Introduction of L. reuteri and Improvement in Social Behaviour

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Introduction of L. reuteri and Improvement in Social Behaviour

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To test the role of L. reuteri in reversing social deficits, it was introduced into the drinking water of MHFD mice (n = 8) for 4 weeks following weaning. Five control conditions were established to ensure that the effects observed were due to the hypothesized reasons. They included:

MHFD offspring + heat-killed L. reuteri (n = 8)

MHFD offspring + PBS solution (n = 3)

MRD offspring + live L. reuteri (n = 10)

MRD offspring + heat-killed L. reuteri (n = 10)

MRD offspring + PBS solution (n = 10)

Metagenomic shotgun sequencing showed that L. reuteri is the bacterial species most dramatically reduced in MHFD offspring, decreased more than nine-fold compared to MRD offspring

Sociability testing showed that MHFD offspring treated with live L. reuteri had restored normal function, as they preferred interacting with the stranger mouse to the same extent as MRD offspring

Social novelty testing showed identical patterns, as MHFD offspring treated with live L. reuteri favoured the newer mouse over the familiar mouse, another sign of social deficits being reversed

In both tasks, MHFD offspring treated with either heat-killed L. reuteri or PBS solution showed no preference for either chamber; indicates that without this active bacterial species in the gut, regular social behaviours are missing

MRD offspring always showed normal results across all conditions (live, heat-killed, PBS) as they already have ample amounts of L. reuteri in their guts before any treatment is administered

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Media Created by Andrea Silva (2017)

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Summary of the Role of Oxytocin As a Mediator 

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Summary of the Role of Oxytocin As a Mediator 

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Media Created by Andrea Silva (2017)

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The experiment failed to rescue certain ASD related symptoms, including repetitive behaviour and anxiety. As well, Buffington et al. (2016) did not explore changes in fear conditioning, which is also related to dopaminergic circuits influenced by L. reuteri. An article by Bruce-Keller et al. (2017) examined anxiety related behaviours directly, as well as fear conditioning. The researchers transplanted gut microbiota shaped by a high fat diet into female mice prior to breeding and observed that the offspring of such mothers, compared to control diet mothers, showed behavioural deficits. This experiment observed anxiety related behaviour in the Open Field Test and found that offspring from high fat diet transplanted mothers spent less time in the inner zone, showing increased anxiety than offspring from control diet offspring. However, this behaviour was observed only in male mice. Bruce-Keller et al. (2017) observed freezing behaviour in a tone test to assess auditory fear conditioning. Freezing response was shown to be reduced in male offspring from high fat diet mothers compared to control diet mothers. Furthermore, the article by Bruce-Keller et al. was also able to show sex-related differences in maternal obesity induced socially deficient offspring. For example, anxiety and marble burying behaviours were only observed in male, and there was no difference in female offspring behaviours between the two groups (3).

The article by Buffington et al. demonstrated whether or not obesity in mothers leads to adverse neurological effects in offspring. There are several components within metabolic syndrome that may also be associated with increased risk of autism in offspring. An article by White et al. (2009) supports that it is not the high fat quality of the diet, but rather the obesity itself, which is necessary to causing the behavioural effects seen in offspring (25). This distinction was not made in the article by Buffington et al. (2016).

When Buffington et al. (2016) tested the effects of oxytocin on social behaviours, they administered it directly and observed the results without accounting for the role that gut microbiota may play in this process. As it has been established that changing the composition of the gut (by introducing L. reuteri) increases oxytocin levels in the brain, it is plausible that the reverse effect (oxytocin influencing contents of microbiota) took place in this experiment. As every other result obtained in this study depended on altering the microbiota in some way, the authors should have more effectively controlled for this possibility before declaring that oxytocin administration on its own can reverse social deficits after interaction.

Bruce-Keller et al. (2009). Figure 3C-D, G-H.

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This article gives insight into how a shift in the gut microbiome as a result of high fat diet induced obesity leads to neurobehavioral deficits in the offspring and was able to successfully identify a specific probiotic candidate, L. reuteri, that rescues social behaviours. Previously, researchers were unable to rescue social behaviours with probiotic treatments

The gut-brain axis: the article thoroughly examines how changes in gut microbiota could lead to impaired social behaviours and draws direct connection to the dopaminergic system. Oxytocin affects social behaviour and is often associated with ASD.

There are many publications that observed the association between maternal obesity and neurodevelopmental deficits in offspring. However, the underlying mechanisms remained under question. This article was able to find a direct link between the high fat maternal diet and neurodevelopmental impairment.

Although the article by Buffington et al. (2016) was one of the first to successfully rescue social deficits with a single bacteria species, articles have since been able to reestablish normal neurobehavioral function through antibiotic treatment. An article published in 2017 by Kang et al. further studied the mechanism behind the gut microbiome to autism association by performing Microbiota Transfer Therapy in children. In an initial 2-week antibiotic treatment and fecal microbiota transplant for following 7-8 weeks, gastrointestinal symptoms and ASD symptoms were assessed overtime. There was seen to be reduction in intensity of gastrointestinal symptoms. As well, autism related symptoms improved after treatment and lasted for 8 weeks post-treatment. As well, as observed in the present study by Buffington et al. (2016) there was an observed increase in diversity of the microbiota community (11).

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The main question asked by the researchers was whether maternal obesity increases risk of neurodevelopmental disorders in offspring. There is growing research in the genetic and environmental factors that lead to these disorders, such as autism spectrum disorder. This article investigated how changes in offspring microbiota arising from maternal high fat diet induced obesity in mice leads to social behavioural deficits in offspring. Maternal obesity has been previously shown to be related to increased chances of ASD in offspring. The researchers hypothesized that a deficiency in social interactions, characteristic of autism, would be seen in offspring of MHFD mice. Through reciprocal social interaction test and the three-chamber test, they found that MHFD offspring in fact had impaired social behaviour. The experimenters show that the gut microbiota of the MHFD offspring was altered, specifically through reduction of essential bacteria species. The results indicate that social deficits can be rescued by co-housing MHFD offspring with MRD offspring, and social behaviour can be improved by treatment of GF mice with MRD fecal microbiota. They found that treatment with a single bacteria species, L. reuteri, reverses social behaviour deficits in MHFD offspring. The experimenters hypothesized that L. reuteri improves social behaviour by enhancing oxytocin levels in the PVN of MHFD mice. As well, direct oxytocin treatment was able to improve social behaviour in MHFD mice.

Previously, Sullivan et al. (2014) have shown that maternal diet influences the neural circuitry of offspring through shaping of the intrauterine environment, thereby affecting offspring behaviour in the long term (21). Furthermore, many studies, including Galley et al. (2014) article have shown that maternal obesity alters microbiome in human toddlers, as well (15). In addition to microbiota remodeling, other physiology affects in offspring have been observed, including impaired insulin resistance in offspring as a result of maternal gestational diabetes and obesity as shown in an article by Maftei et al (15). In the present Buffington, et al. (2016) experiment, L. reuteri was shown to increase in oxytocin levels in Paraventricular nuclei (PVN) of hypothalamus, which projects to the Ventral tegmental area (VTA). The VTA and nucleus accumbens (NAc) are associated with the reward system and modulate social behaviours. In socially impaired mice, LTP in the VTA was affected. Previous and current studies have focused on the effect of maternal-high fat diet induced inflammation in the offspring brain. A study by White et al. (2009) high fat diet was associated with nitric oxide synthase, as well as IL-6 and Iba-1 and GFAP in offspring, indicating increased inflammatory signalling (24).

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MHFD offspring had fewer social interactions, impaired sociability and reduced preference for social novelty compared to MRD offspring.

MHFD in mothers led to change in microbiome composition and a reduction in diversity of offspring microbiota.

Co-housing rescued social behaviours and microbiota profile of MHFD offspring but failed to rescue marble burying, which reflects repetitive behaviour (ASD).

Microbial reconstitution through fecal transplants effectively improved social behaviour in GF mice.

Treatment with L. reuteri treatment rescued social behaviour in MHFD offspring, but had no effect on anxiety and repetitive behaviours.

L. reuteri -treated MHFD offspring had increased number of oxytocin-expressing cells than control MHFD control offspring.

Upon interaction with stranger mice, MRD offspring had increased LTP in the VTA and long-lasting enhancement in the dopaminergic reward pathway. In contrast, MHFD offspring had reduced interaction and weakened in the VTA.

L. reuteri treatment rescued reciprocal social interaction and induced changes in synaptic strength in the VTA of MHFD offspring.

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Experiment 4: Colonization of Germ-Free Mice with the Microbiota from MRD, but Not MHFD Mice, Reverses Their Deficient Social Behavior

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Experiment 4: Colonization of Germ-Free Mice with the Microbiota from MRD, but Not MHFD Mice, Reverses Their Deficient Social Behavior

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GF mice have a cleared microbiota, therefore if lack of bacteria causes defective social behaviour, then GF mice would be socially deficient. As expected, social behaviour in GF mice was impaired, as observed in the reciprocal interaction test and the three-chamber test.

Fecal microbiota from adult MRD and MHFD were transplanted to offspring into 4w and 8w GF mice. After transplantation of MRD microbiota, 4w GF mice showed normal social behaviour, but there was little change in 8w mice. After MHFD transplantation, both age groups remained impaired.

Buffington et al. 2016. Figure 3G-J.

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Experiment 3: Gut Microbiota Mediate MHFD-Induced Social Deficits 

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Experiment 3: Gut Microbiota Mediate MHFD-Induced Social Deficits 

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The researchers co-housed the mice, which affects the microbiota through the fecal-oral route, and after 3 weeks, observed if social deficits in MHFD offspring are improved.

Control cages had either 4 MHFD or 4 MRD mice. Fecal samples were collected and social behaviour was observed in both mice at age 7-8 weeks.

MHFD mice co-housed with MRD mice had normal reciprocal social interactions and the 3-chamber test showed normal sociability and preference for social novelty. There was a correction the microbiota of MHFD offspring to resemble that of MRD offspring.

Buffington et. al. 2016. Figure 2C-F.

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Experiment 2: Dysbiosis of The Gut Microbiota in MHFD 

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Experiment 2: Dysbiosis of The Gut Microbiota in MHFD 

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16S ribosomal RNA gene sequencing was performed on fecal samples from MRD and MHFD offspring.

The gut microbiota of both MRD and MHFD offspring were dominated by Bacteroidetes and Firmicutes.

There was a notable difference between the bacterial community structures. Diversity of microbiota was decreased in MHFD offspring (1J).

Buffington et. al. 2016. Figure 1J.

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Summary of the Three-Chamber Test for Sociability and Social Novelty 

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Summary of the Three-Chamber Test for Sociability and Social Novelty 

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Media Created by Parnian Dolati (2017)

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Experiment 1: Social Behaviours Are Impaired in MHFD 

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Experiment 1: Social Behaviours Are Impaired in MHFD 

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When MRD mice and MHFD mice were assessed in an arena with an unfamiliar mouse, MRD offspring was shown to have greater reciprocal interaction time and contact duration than MHFD offspring (Fig. 1B-D).

The three-chamber test demonstrated that MRD offspring spent more time interacting with an unfamiliar mouse than the empty cage; whereas, the MHFD offspring was interested in the empty wire cage. Likewise, the MRD offspring had more interest in a stranger mouse in the test for social novelty, while MHFD preferred the familiar mouse (Fig 1F-G).

Buffington et. al. 2016. Figure 1B-D, F-G.

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The Party: a virtual experience of autism – 360 film

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Image from: https://i1.wp.com/allergiesandyourgut.com/wp-content/uploads/2017/01/gut-brain-disease.jpg

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Image from: https://villa-medica.com/wp-content/uploads/2017/07/villa-medica-autism-spectrum-disorder-facts-and-early-signs-2-compressor.jpg

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Oxytocin is often referred to as the cuddle hormone as it is released when people bond socially

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There is a negative correlation between ASD and oxytocin levels, where ASD is associated with decreased levels of oxytocin (19)

This is specially true in the paraventricular nuclei (PVN) where oxytocin is synthesized (1)

From the PVN, oxytocin is projected to the VTA, which responds to rewarding stimuli attained from social interactions (something that is lacking in ASD patients) (1)

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Previous studies show evidence that maternal obesity leads to social interaction deficits (seen in those with ASD) and ultimately causing changes in the levels of oxytocin and VTA plasticity in the brain - all because of dysbiosis in the gut

None have yet to single out specific microbiota that can reverse the ASD effects in offspring

GOAL: To further investigate the link of maternal obesity on social interaction, oxytocin levels and VTA plasticity of offspring and isolate a strain of bacteria that can possibly reverse these effects

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Image Created by Andrea Silva (2017).

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How Is Changes In Gut Affecting The Brain?

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How Is Changes In Gut Affecting The Brain?

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A: Gut-Brain Axis

The gut and the brain interact with each other bi-directionally through cellular signalling via the vagus nerve

It serves an important role in maintaining homeostasis in one's body (11, 14, 23)

Changing one's diet to supplement specific microbiota in the gut or the removal of all bacteria may influence a stress response, as seen in an experiment done to mice

The gut can also influence many of the brain's 'thought-to-be' roots such as behaviour, cravings, and mood. (17)

In a more brain intricate level, the gut can play a role with myelination and neurogenesis (17)

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Maternal Obesity --> Offspring Dysbiosis --> ASD-Like Indicators

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Maternal Obesity --> Offspring Dysbiosis --> ASD-Like Indicators

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Mothers that are obese are 1.5 time more likely to deliver a child that suffers from ASD

Maternal obesity causes an alteration in one's gut microbiome

Overweight mothers deliver offspring with altered bacterial composition in comparison to offsprings born from healthy weight mothers

A reduction is seen in proteobacteria (Escherichia, Klebsiella, and Enterobacter)

Maternal obesity is a growing issue in North America impacting all --specially, childbearing aged women, who 35% of them are obese (12, 13, 16, 19)

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Image from: https://cdn-images-1.medium.com/max/500/1*A1UTzUNkEao08ptaFBrNLA.jpeg

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We need it, and it needs us

The microbiome is composed of microorganisms (mainly bacteria) that reside in one's intestines and in turn aid with the digestion of food, production of vitamins, regulation of the immune system and protection against disease-causing bacteria. (10)

A disruption or changes in this microbiome (otherwise known as dysbiosis) can have a great influence on the development of certain neuronal disorders such as ASD by changing not only the physiology of the gut, but interfere with immune regulation and behaviour. (10)

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Along with the 3 major indicators of ASD (communication, social and behavioural deficits), GASTROINTESTINAL issues are commonly present among those who suffer from ASD (22)

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ASD is associated with other genetic-caused syndromes...

1. Fragile X Syndrome (FMR1 gene)

2. Tuberous Sclerosis Complex Syndrome (TSC1/2 gene)

3. Rett's Syndrome (CNTNAP2 gene)

Example: If a child is diagnosed with ASD, and then they are diagnosed with Tuberous Sclerosis, the child will still have ASD, but now the cause of the ASD is identified (i.e. a mutation in the TSC1 or TSC2 gene).

Mutations in the genes listed above can cause a disruption in cell function in the nucleus, cytoplasm or membrane level LEADING to neuronal structural differences, such as dendritic spine variances. (18, 20)

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What is ASD?

ASD is a neurodevelopmental disorder characterized by an array of conditions that display challenges in communication,  social interactions, and repetitive behaviour (22)

It affects every 1 in 45 child in North America (1 in 68 in the worldand it affects four times more boys than girls (22)