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Microbial Cross-Feeding Scores Uncover Interactions That Influence Gut Health

The team developed a computational metabolite exchange scoring system to identify microbial cross feeding relationships–the use of metabolites produced…

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An international research team led by scientists at the Hudson Institute of Medical Research has found a way to determine which species of gut microbiota are important in certain diseases, and how they interact with other microorganisms to create a healthy microbiome.

The team developed a computational metabolite exchange scoring system to identify microbial cross feeding relationships—the use of metabolites produced by one microorganism as an essential nutrients by another—and how these may be altered in disease. The researchers suggest that understanding such relationships could point to therapeutic approaches for a range of disorders including inflammatory bowel disease, infections, autoimmune diseases and cancer.

“There are roughly 1000 different bacterial species in a healthy gut—it’s a microscopic multicultural community with over a trillion individual members,” said research lead Samuel Forster, PhD. “Bacteria in our microbiomes exist as communities that rely on each other to produce and share key nutrients between them … We have developed a new computational way to understand these dependencies and their role in shaping our microbiome. This new method unlocks our understanding of the gut microbiome and provides a foundation for new treatment options that selectively remodel microbial communities.”

Associate Professor Samuel Forster from Hudson Institute of Medical Research is developing new ways of understanding interactions within the human gut microbiome. [Hudson Institute of Medical Research]
Forster’s team, working with collaborators at the Institute for Systems Biology, and at Monash University and Monash Health, reported their findings in Nature Communications, in a paper titled “Disease-specific loss of microbial cross-feeding interactions in the human gut.” In their paper the team concluded, “We propose that our conceptual framework will help prioritize in-depth analyses, experiments and clinical targets, and that targeting the restoration of microbial cross-feeding

interactions is a promising mechanism-informed strategy to reconstruct a healthy gut ecosystem … We show that our analytical framework identifies both known and novel microbiome-disease associations, providing a cost-efficient and mechanistically grounded strategy to prioritize experiments and guide clinical trials.”

The human gut contains hundreds of microbial species forming a complex and interdependent metabolic network, the authors explained. And more than half of the metabolites consumed by gut microbes are by-products of microbial metabolism, with the waste of one species serving as nutrients for other. This means that the loss of one species may impact on the survival or extinction of others. “Species interdependence can render microorganisms vulnerable to local extinction if a partner is lost unless alternative species are available to fill that niche,” the team continued. “Many gut microorganisms critical to human health rely on nutrients produced by each other for survival; however, these cross-feeding interactions are still challenging to quantify and remain poorly characterized.”

Forster and colleagues have spent years studying the gut microbiome and working out which species perform which functions. To help understand the link between cross-feeding interactions and disease, the team developed a computational metabolite exchange score (MES) that can quantify microbiome interactions. The system is designed to identify those microbial cross-feeding interactions that are most affected in disease. “MES is the product of the diversity of taxa predicted to consume and taxa predicted to produce a given metabolite, normalized by the total number of involved taxa,” the authors noted.

For their reported study, and to obtain an overview of the association between cross-feeding interactions and different diseases, the team applied the MES technique to exiting datasets. “To obtain an overview of the association between cross-feeding interactions and different diseases, we performed a large-scale analysis of 1661 high-quality and deeply sequenced gut metagenome samples, including 871 healthy and 790 diseased individuals from 33 published studies, 15 countries and 11 disease phenotypes,” they wrote. Using the MES platform the team was able to identify and rank metabolic interactions that were significantly affected by loss of cross-feeding partners in 10 out of 11 diseases.

For example, hydrogen sulphide was highlighted as a key factor in Crohn’s disease (CD). The investigators discovered that the association may relate to loss of bacteria that use hydrogen sulphide, H2S, not an increase in those species producing it, as was previously believed. “Our results suggest that CD patients lack microbial community members to support a healthy H2S balance,” they wrote. The study in addition identified other associations between the microbiome interactions and disease, including some that hadn’t previously been known.

“Our framework identified both known and novel microbiome-disease associations, including a link between colorectal cancer and the microbial metabolism of ethanol, a connection between rheumatoid arthritis with microbially-derived ribosyl nicotinamide, and links between Crohn’s disease and specific bacteria that metabolize hydrogen sulfide,” the investigators further noted. “… we found that H2S—a gas previously implicated in CD and IBD symptoms—was the metabolite most affected by the loss of cross-feeding microbial partners … .”

First author Vanessa Marcelino, PhD, says the new computational method for studying microbial communities was key to establishing the relationships. “This is a significant step in the development of complex microbial therapies. This approach allows us to identify and rank the key interactions between bacteria and use this knowledge to predict targeted ways to change the community.”

Forster and team have a long-standing relationship with Adelaide-based biotechnology company BiomeBank, which is working on new ways to treat and prevent disease by restoring gut microbial ecology. He commented, “Through the partnership between the Hudson Institute of Medical Research and BiomeBank, these insights into community structure will provide the opportunity for targeted intervention with rationally selected combinations of microbes,” Forster said. In their paper the team concluded, “We expect that metagenome-informed metabolic models, coupled with an assessment of microbial cross-feeding interactions, will help alleviate one of the main barriers in the development of microbiome therapies—prioritizing which species or metabolites to target. By focusing on restoring key aspects of the gut ecology, we may be able to introduce more effective and long-lasting changes in the human gut microbiome.”

The post Microbial Cross-Feeding Scores Uncover Interactions That Influence Gut Health appeared first on GEN - Genetic Engineering and Biotechnology News.

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Dozens Of Major Companies Say 2024 Will Be The Year Of Cost Cutting

Dozens Of Major Companies Say 2024 Will Be The Year Of Cost Cutting

We already know that the Biden administration and the BLS are ignoring…

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Dozens Of Major Companies Say 2024 Will Be The Year Of Cost Cutting

We already know that the Biden administration and the BLS are ignoring the massive layoffs happening across corporate America in favor of pushing some asinine narrative that 'Bidenomics', whatever that even means, is somehow creating jobs other than 2nd and 3rd jobs for senior citizens driving Uber when they should be retired. 

Now, it's becoming clear that 2024 could be the year when corporations continue 'cost cutting', which could mean a number of strategies, almost all of which result in less employees and less pay instead of more. 

Executives from various industries, including toy, cosmetics, and technology sectors, are cutting costs and jobs, even in profitable companies such as Mattel, PayPal, Cisco, Nike, Estée Lauder, and Levi Strauss, CNBC wrote this week.

Macy's plans to shut five stores and cut over 2,300 jobs, while airlines like JetBlue and Spirit offer buyouts, and United reduces in-flight services. This trend is driven by consumer caution and investor pressure for companies to adapt to changing demand and higher expenses, the report says.

Significant labor contracts in sectors like airlines and UPS have raised costs, challenging businesses accustomed to passing these on to consumers. Remember those celebrations people were having about UPS drivers winning their new contracts just months ago? UPS is already laying off drivers as a result.

Walmart is expanding its store network, contrasting with the broader cost-cutting movement. Major banks have already reduced their workforce significantly, anticipating economic shifts. U.S. companies announced significant job cuts in January, indicating a focus on profit optimization amid steady earnings reports without relying on substantial price or sales increases.

A full list of major companies that have laid off workers or implemented strategies to cut costs include:

  • Mattel
  • PayPal
  • Cisco
  • Nike
  • Estée Lauder
  • Levi Strauss
  • Macy’s
  • JetBlue Airways
  • Spirit Airlines
  • United Airlines
  • UPS
  • Meta (parent of Facebook and Instagram)
  • Amazon
  • Alphabet (parent of Google)
  • Microsoft
  • Warner Bros. Discovery
  • Disney
  • Paramount Global
  • Comcast (parent company of NBCUniversal)
  • Delta Air Lines
  • General Motors
  • Ford Motor
  • Stellantis
  • Chipotle
  • Wells Fargo
  • Goldman Sachs
  • Walmart
  • Target
  • Home Depot

Meta's restructuring in 2023 set a precedent for tech giants like Amazon, Alphabet, Microsoft, and Cisco to reduce their workforces. But the trend extends beyond tech, with UPS cutting 12,000 jobs and others in retail and entertainment also announcing layoffs.

Significant cost savings have been announced by major corporations, including Warner Bros. Discovery and Disney, with the latter aiming for $7.5 billion in savings.

Paramount Global and NBCUniversal have also trimmed their staffs. Cost-cutting measures have reached various sectors, including airlines adjusting services and deferring expenses, and automakers scaling back investments due to challenges in demand and EV adoption.

“You’re seeing a rebalancing happening in the labor markets, in the capital markets. And that rebalancing is still going to play out and gradually lead to a more sustainable environment of lower inflation and lower interest rates, and perhaps a little bit slower growth, said Gregory Daco, chief economist for EY.

He continued, telling CNBC: “You are in an environment where cost fatigue is very much part of the equation for consumers and business leaders. The cost of most everything is much higher than it was before the pandemic, whether it’s goods, inputs, equipment, labor, even interest rates.”

Even Chipotle is experimenting with robots to boost efficiency. These adjustments reflect a broader recalibration after the pandemic's disruptions, with companies aiming for a sustainable balance in a potentially slower economic growth environment.

Tyler Durden Wed, 02/21/2024 - 05:45

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Walmart Hits Record High After Earnings Beat, Despite Soft Guidance, Warning About “Choiceful” Consumers Spending Less

Walmart Hits Record High After Earnings Beat, Despite Soft Guidance, Warning About "Choiceful" Consumers Spending Less

Walmart shares hit…

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Walmart Hits Record High After Earnings Beat, Despite Soft Guidance, Warning About "Choiceful" Consumers Spending Less

Walmart shares hit a new all-time high after the largest bricks and mortar retailer reported earnings that beat expectations despite providing guidance that was marginally softer, as choosy shoppers nevertheless kept buying in its stores.

Here is what the company report for the final quarter of 2023:

  • Adjusted EPS $1.80 (excluding impact, net of tax, from a net gain of $0.23 on equity and other investments) vs. $1.71 y/y, beating estimate of $1.65
  • Revenue $173.39 billion, +5.7% y/y, beating estimate $170.66 billion
    • Total US comparable sales ex-gas +3.9%, estimate +3.2%
    • Walmart-only US stores comparable sales ex-gas +4%, estimate +3.12%
    • Sam's Club US comparable sales ex-gas +3.1%, estimate +2.99%
  • Change in US E-Commerce sales +17%, beating estimate +15.5%
  • Adjusted operating income $7.25 billion, beating estimate $6.79 billion

Of the metrics reported, however, the most important one is that Walmart’s same-store sales (ex fuel), rose 4% YoY for US stores (of which net sales was 3.% and eCommerce added 17%). Wall Street was expecting 3.1% so the number was clearly a beat and was driven by "strength in grocery, health and wellness, offset by softness in general merchandise", and was the result of higher transactions (+4.3%) offsetting average ticket prices, which dropped 0.3% YoY. Still, the number is a far cry from the 8.3% comp sales a year ago.

In keeping with the noted softness in general merchandise, the world’s largest retailer delivered softer guidance for the current fiscal year, as it expects consumers to be selective in their spending:

  • For full-year 2025, WMT sees
    • Net sales +3% to +4%, slower than growth from the prior year, and adjusted EPS $6.70 to $7.12, slightly disappointing vs the median consensus estimate of $7.09
    • Capital expenditures approximately 3.0% to 3.5% of net sales
  • For Q1, 2025, WMT sees sees adjusted EPS $1.48 to $1.56.

Discussing the quarter, CEO Doug McMillan said that "we crossed $100 billion in eCommerce sales and drove share gains as our customer experience metrics improved, evenduring our highest volume days leading up to the holidays"

Commenting on customer "selectivity", CFO John Rainey said that “they are being choiceful" as consumers continue to spend less per trip but have been shopping frequently, adding that the company expects some resilience to continue for the rest of the year.

There was more good news: Walmart is gaining share in nearly every category, according to Rainey, with e-commerce among the factors driving growth as the company trims losses associated with handling online orders. Furthermore, while deflation is still a possibility, the company expects it to be less likely based on what it observed during the latest quarter.

That said, while grabbing more spending with low-priced groceries and other basics, Walmart has been cautious in recent months about the health of the consumer amid persistent inflation and higher interest rates. As noted above, US consumers have been buying cheaper products and seeking value, as they pull back from discretionary products like general merchandise. That has resulted in softer sales for some retailers, including Target Corp. and Home Depot Inc. Other big-box retailers are set to report their quarterly earnings in the coming weeks.

As Bloomberg notes, the recent moderation in inflation is another challenge for Walmart and other retail operators that have passed down price increases to consumers over the past few years. This has contributed to higher dollar sales for companies, followed by an uptick in revenue during the pandemic when people bought more groceries and home goods. Such increases are slowing overall, though inflation remains stubborn in some areas like groceries and shelter.

Similar to all of its major competitors, Walmart has been beefing up automation in warehouses and stores in recent years, while remodeling locations to make them more modern. Pickup and delivery businesses continue to expand, driving share gains among upper-income households and fueling growth of the Walmart+ membership program.

Separately, Walmart said it agreed to buy smart-TV maker Vizio Holding Corp. for about $2.3 billion. The deal would accelerate the retailer’s advertising business, called Walmart Connect, and help Walmart and its advertisers engage more with customers. Walmart has been expanding Walmart Connect and other nonretail businesses that have faster growth and better margins. The deal announcement confirmed a Wall Street Journal report from last week. Vizio shares soared 15% in Tuesday premarket trading.

As for WMT, the Bentonville, after the stock gained 16% over the past year, it jumped another 5.7% on Tuesday rising to a new all time high as investors were clearly satisfied with what they saw.

Full investor presentation below (pdf link)

Tyler Durden Tue, 02/20/2024 - 10:17

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Estimating US Recession Risk Using Economic Data For States

What are the choices for monitoring and estimating recession risk? Slightly lower than the number of stars in the universe. Ok, I’m exaggerating, but…

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What are the choices for monitoring and estimating recession risk? Slightly lower than the number of stars in the universe. Ok, I’m exaggerating, but not much. The good news: the search for robust, relatively reliable indicators narrows the field dramatically. But there’s always more to learn, in part because the supply of data sets is vast, increasingly so. Which brings me to another indicator that looks promising: state coincident indexes.

Every state’s economy is, in some degree, unique, although the gravitational pull of the national economy casts a long shadow. Tracking each state economy separately, and then aggregating the results, provides a different spin on the US business cycle compared with national indicators. Think of it as a bottom-up model vs. the standard top-down approach via US retail sales, industrial production, etc.

Conveniently, the Philly Fed publishes monthly coincident indicators for each state. Aggregating the 50 signals into a composite index provides a somewhat different view of the US business cycle vs. traditional top-down metrics. There are several ways to process the numbers – my preference, shown in the chart below, is a 3-month-change model. If a state’s 3-month change is negative (positive), the signal is negative (positive). Summing the negatives and positives provides a national profile. The current reading is 0.48 — in other words, 48% of the states are posting negative 3-month changes for their respective coincident indicator. As shown below, the composite reading maps fairly closely with NBER-defined downturns, and so the current signal is issuing a warning, albeit a warning that has yet to provide what might be thought of as passing the point of no return. But it’s close.

The readings vary from 0 (no negative 3-month changes) to 1.0 (all 50 states are reporting negative 3-month changes). A quick review of the historical record suggests that the US is on the verge of slipping into recession.

But before we ring the alarm bell, there are some caveats to consider. First, a similarly high reading 20-plus years ago turned out to be a false signal. The next couple of months will likely determine if a repeat performance is brewing, or not.

Second, no one indicator is flawless, as we’ve learned over the last couple of years – especially in recent history, when pandemic-related events have created no shortage of macro surprises.

Another reason to reserve judgment, at least for now: a range of other business cycle indicators tracked in The US Business Cycle Risk Report (a sister publication of CapitalSpectator.com) continue to show a clear growth bias. But as reported in this week’s issue, there are some nascent signs of softer economic activity and so it’s possible that the coincident state indicators are an early warning that the tide is shifting.

The most reliable methodology for estimating recession risk in real time is building an ensemble model that combines various modeling applications that are complimentary. Although any one model will excel at a given point in time, quite often the best-performing indicator changes through time. To minimize the risk that’s inherent in any one signal, The US Business Cycle Risk Report crunches the numbers on multiple indicators, which has proven to be close to optimal for balancing the need for timely signals that minimize false signaling.

Despite the caveats, the coincident state model adds another dimension to the mix and provides some complimentary input to The US Business Cycle Risk Report’s existing suite of indicators. Accordingly, I’ll be adding the composite state coincident data to the newsletter’s weekly updates.

The next batch of coincident state updates for January is scheduled for later this month. Meantime, I’ll be carefully reviewing the incoming data for fresh clues that support or reject the suggestion that trouble’s brewing via the state coincident indicators.


How is recession risk evolving? Monitor the outlook with a subscription to:
The US Business Cycle Risk Report


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