Probiotics and GI Function in Pregnancy

Researchers at University of California-Davis recently showed that a commercial probiotic reduced nausea, vomiting, and constipation in 32 pregnant women. At enrollment, the women (age 31.6 ± 3.9 years), all in the first trimester of pregnancy, experienced a mean incidence of nausea of 7.0 ± 5.5 times per day and 10.3 ± 6.6 hours; the mean nausea score (1-5) was 3.6 ± 0.9. Twelve of the women vomited a mean of 2.0 ± 1.3 times per day; the mean vomiting score was 2.8 ± 1.0.

The 16-day study consisted of two cycles during which Probiotics 10 (Nature’s Bounty, Ronkonkoma, NY) was taken daily for six days followed by two days without the supplement. The probiotic contained inulin (200 mg), nine Lactobacillus strains, and Bifidobacterium lactis Bl-04. The participants completed a daily survey that tracked GI symptoms (nausea, vomiting, constipation), energy level, and quality of life. Fecal samples were also taken, allowing the researchers to investigate gut metabolites, fecal microbiota, and bacterial genes.

Probiotic intake significantly reduced nausea incidence by 16%, nausea hours by 16%, and vomiting incidence by 33%. Stool hardness, a sign of constipation, also decreased. Quality of life measures, including ability to prepare meal, reactivity to smells, fatigue, moodiness, improved.

The researchers reported some interesting associations between biomarkers found in stool samples and symptoms. Patients with high fecal α-tocopherol levels at baseline had low vomiting scores throughout the study. Also, vomiting incidence directly associated with the amount of Akkermansia bacteria in fecal samples. Probiotic intake decreased Akkermansia levels and increased α-tocopherol levels, although the changes were not statistically significant due to small sample size.

The researchers also looked for butyric acid-producing genes and bile acid-producing genes in fecal samples. While neither the butyric acid-producing genes (bcoA and buk) nor the bile acid-producing gene baiJ was affected by probiotic intake, the bile acid gene bsh (bile salt hydrolase), which generates free bile acids, was: “…the copy number of bsh increased significantly by 5.41-fold due to probiotic intake.” Low bsh was associated with high vomiting scores. Bile acids, produced by gut microbial enzymes and by the liver, “regulate smooth muscle contraction, defecation, and sensation in addition to lipid metabolism and absorption.” Both Lactobacillus and Bifidobacterium generate bile salt hydrolase.

The authors call for further investigation into the use of probiotics and their effect on bile acid during pregnancy. This study was neither randomized nor placebo controlled, and it did not look at long-term, possibly cumulative effects of probiotic supplementation.

Liu AT, et al. Probiotics Improve Gastrointestinal Function and Life quality in Pregnancy. Nutrients. 2021;13:3931

Microplastics and Pregnancy

Plastic is causing an ever-growing list of negative health effects. For years, studies have documented the endocrine-disrupting effects of plastic chemicals; such studies have shown an association between endocrine-disrupting compounds (EDCs) and infertility and gestational disorders, including miscarriage, preeclampsia, and fetal growth restriction. In addition to disrupting hormone-guided physiology, a 2021 Australian study, led by John E. Schjenken, reports that EDCs affect the maternal immune response to pregnancy that permits embryo implantation and placenta development. But the chemicals are only part of the health issue; microplastics are another problem.

A 2020 Italian study, led by Antonio Ragusa, found microplastic fragments in four placentas taken from healthy women who had a vaginal delivery. Microplastics (MPs), particles smaller than five millimeters, result from plastic degradation in the environment. These minute bits of plastic also have commercial uses. MPs have been found in marine life and in human intestines, but this is the first evidence of MP affecting the human fetus.

The Italian researchers collected three samples, each weighing 23.3 ± 5.7 grams, from each placenta (total weight is about 600 g): one from the maternal side, one from the fetal side, and one from the chorioamniotic membranes. Using Raman microspectroscopy, they found 12 plastic fragments (ranging from 5 to 10 μm): four in the maternal side, five in the fetal side, and three in the membranes. The fragments were small enough to be transported in the bloodstream; the fragments could have entered the mother’s body via ingestion or inhalation. The Italian researchers say, “…MPs may accumulate and exert localized toxicity by inducing and/or enhancing immune responses and, hence, potentially reducing the defence mechanisms against pathogens and altering the utilization of energy stores.” They also suggest that MP presence may have transgenerational effects on metabolism and reproduction. Studies are needed to identify possible adverse effects on immune responses and pregnancy issues.

Babies are also exposed to significant amounts of microplastics from plastic (polypropylene) bottles. A team of Irish researchers looked at the amounts of MPs released from polypropylene infant-feeding bottles (PP-IFBs) when World Health Organization recommendations for cleaning and sterilizing the bottles and mixing up baby formula were used. They quantified MP-release from ten different polypropylene infant-feeding bottles, “accounting for 68.8% of the global market.” Bottles with polypropylene bodies (n=8) released from 1,310,000 ±130,000 to 16,200,000 ± 1,300,000 particles per liter—far above 1000 particles that WHO deems “low risk.” Heat and agitation during cleaning/sterilization and the heating of formula or breast milk cause MPs to be released from the bottle. Microwave heating is particularly problematic because it produces “pockets of superheated water” that cause higher MP generation. Breast pumps with plastic parts can also degrade during cleaning and sterilization. Old fashion, glass bottles without plastic parts, of course, cannot produce MPs.

Endocrine and immune effects are not the only health issues with MPs. A 2021 study from the New Jersey Institute of Technology found that some bacteria found in wastewater plant sludge become antibiotic resistant when exposed to microplastic: “…certain strains of bacteria elevated antibiotic resistance by up to 30 times while living on microplastic biofilms….” The researchers collected sludge samples from three New Jersey wastewater treatment plants and inoculated the samples with polyethylene and polystyrene microplastics in order to identify which bacteria tend to grow on MPs. They also tracked genetic changes in the bacteria. Genes related to resistance to sulfonamides (a common type of antibiotic) increased up to 30 times with MP exposure, compared to sand-biofilm controls. When the antibiotic sulfamethoxazole was added to the sample, the antibiotic resistance genes further increased by up to 4.5-fold. Dung Ngoc Pham, first author of the study, told PHYS.org, “’Previously we thought the presence of antibiotics would be necessary to enhance antibiotic-resistance genes in these microplastic-associated bacteria, but it seems microplastics can naturally allow for uptake of these resistance on their own….The presence of antibiotics does have a significant multiplier effect however.’”

A quick look at Scholar.Google shows that microplastic pollution and bioremediation of the environment is a growing topic—and probably a long way off. Consumers need to be aware that these fragments are making their way into our bodies and lessen exposure whenever possible.

Jenkins J. New study shows microplastics turn into ‘hubs’ for pathogens, antibiotic-resistant bacteria. Phys.org. March 19, 2021.

Li D, et al. Microplastic release from the degradation of polypropylene feeding bottles during infant formula preparation. Nature Food. 2020;;1: 746-754.

Ragusa A, et al. Plasticenta: First evidence of microplastics in human placenta. Environment International. 2021; 146; 106274.

Schjenken JE, et al. Endocrine Disruptor Compounds – A Cause of Impaired Immune Tolerance Driving Inflammatory Disorders of Pregnancy? Frontiers in Endocrinology. April 2021;12:article 607539.

Jenkins J. New study shows microplastics turn into ‘hubs’ for pathogens, antibiotic-resistant bacteria. Phys.org. March 19, 2021.

Exposure to Nature and Children’s Immune Function

Finnish researchers recently conducted a study that showed exposure to nature’s biodiversity affects human commensal microbiota and immune function. The study involved 75 children (ages 3-5 years), living in one of two cities with populations over 100,000 people. None of the children were taking probiotics or antibiotics. The children attended a nature-oriented daycare (n=23); a standard, unmodified, urban daycare with gravel and little or no greenspace (n=16); or an “intervention” urban daycare (n=36)—standard urban daycares with forest floor (100 m²), sod (200 m²), peat blocks for climbing and digging, and planters added to their yards. The forest floor included vegetation (dwarf heather, blueberries, crowberry, mosses, and meadow grass).

Daycare workers encouraged children to have contact with the vegetation and natural materials during their time outdoors (0.5 to 2 hours twice a day; average 1.5 hours/day). Although the researchers could not control for home diet, they did have a central kitchen in each city prepare breakfast, lunch, and an afternoon snack for all the participants during the 28-day study (May to June 2016). The researchers looked at skin bacterial diversity, gut bacteria, and plasma cytokine changes in the three groups of children.

Before daycare yards were modified with vegetation, the children in the urban group and the intervention group had similar composition of the bacteria on their skin, including similar Proteobacterial communities. At the end of the 28 days, the intervention group had more diverse Proteobacterial and Gammaproteobacterial communities, similar to children attending nature-oriented daycares.

Greater skin Gammaproteobacterial diversity was associated with higher transforming growth factor β1 (TGF-β1) plasma concentration; TGF- β1 “is a multifunctional cytokine that down-regulates inflammatory processes, particularly in the gut-associated immune system.” High Gammaoproteobacterial diversity in the skin microbiome is also associated with increased IL-10 plasma concentrations; IL-10 is an anti-inflammatory cytokine. By study’s end, children in the intervention group had an increased IL-10:IL-17A ratio (more anti-inflammatory cytokines than pro-inflammatory cytokines). The researchers suggest, “…providing children with a chance for daily contact with diverse vegetation and dirt in safe urban green spaces…might improve child health by activating the regulatory pathways of the immune system. This could reduce overactive immune responses and, consequently, decrease the risk of developing immune-mediated diseases.”

The intervention also changed gut bacteria composition. The relative abundance of Clostridiales decreased in the intervention group, compared to standard daycare participants; and alpha Rumioncoccacea communities became “slightly more divergent” after the 28 days. Ruminococcaceae contains butyrate-producing species. Interestingly, the forest floor and sod used in the intervention spaces did not contain the Ruminococcaceae strains found in children’s stool samples. The researchers think the transplantation of the green materials may have rejuvenated microbial communities that were basically dormant: “We recommend following the effects of biodiversity intervention over a longer period to understand the microbial community dynamics on daycare yards and to see the longevity of changes in plasma cytokines.”

Roslund MI, et al. Biodiversity intervention enhances immune regulation and health-associated commensal microbiota among daycare children. Sci Adv. October14, 2020; 6: eaba2578.

Heavy Metals, Trace Elements, and Childhood Blood Pressure

While many studies have correlated a single metal or element to a health outcome, trying to track nonlinear associations between metal-element combinations has been problematic. In June 2020, Johns Hopkins researchers published a study that used data from the Boston Birth Cohort (enrolled 2002-2013) and a newer statistical method, Bayesian kernel machine regression (BKMR), to examine the effect of metal co-exposures on children’s blood pressure. Higher blood pressure during childhood is associated with cardiovascular disease and hypertension in adulthood.

The researchers included 1,194 mother-child dyads in their analysis. Blood samples taken from the mothers 24 to 72 hours after delivery provided red blood cell concentrations of three heavy metals (lead, mercury, cadmium) and two trace minerals (selenium, manganese). They looked for associations between these concentrations and the offspring’s blood pressure taken at the most recent wellness visit. The researchers also collected data on the health during pregnancy, socioeconomic factors, fish consumption, and cigarette smoking.

Although the researchers did not find an association between child blood pressure and either lead or mercury, cadmium (Cd) levels did directly correlate with child systolic blood pressure when manganese (Mn) levels were low and “inverse association between Mn and child SBP was stronger at higher levels of Cd.” Smoking is a known source of Cd exposure. The researchers found that Cd concentration in smoking mothers (median = 1.41 μg/L) was over twice the concentration in those who did not smoke or who quit before pregnancy (median = 0.65 μg/L). If the smoking mother also had a higher concentration of Mn in her blood, her child’s systolic blood pressure (SBP) tended to be lower than children born of smokers with lower Mn levels—but not as low as SBP found in children with non-smoking mothers.

In a commentary on this study Breton and Farzan ask, “As more evidence emerges showing interactions between trace elements and metals in pregnancy, should we more seriously consider targeted use of essential elements in populations with known high exposures to potentially toxic metals? Might nutritional intervention mitigate risk?”

Breton CV, Furzan SF. Invited Perspective: Metal Mixtures and Child Health: The Complex Interplay of Essential and Toxic Elements. Environmental Health Perspectives. June 2021;129(6).

Zhang M, et al. In Utero Exposure in Heavy Metals and Trace Elements and Childhood Blood Pressure in a US Urban, Low-Income, Minority Birth Cohort. Environmental Health Perspectives. June 2021;129(6).